Research papers pulled from Sanity

Allen, N., Alshakhouri, M., Daldegan-Bueno, D., Donegan, C. J., Evans, W. J., Forsyth, A., Hoeh, N. R., Menkes, D. B., Muthukumaraswamy, S., Ponton, R., Reynolds, L. M, Roop, P., Smith, T., Sumner, R. L., Sundram, F.

This open-label Phase IIa trial (n=19, 15 male) found that an 8-week regimen of microdosed LSD (8μg initially, then 6-20μg twice weekly) for major depressive disorder was well-tolerated with no serious adverse events or cardiac valvulopathy, achieved 59.5% reduction in MADRS scores sustained for six months, and had only one withdrawal due to anxiety.

Beaussant, Y., Brennan, C., Kristan, I., Ljuslin, M., Macdonald, D., Mazzola, E., Murphy, M. E., Nigam, K., Rinaldi, A. D., Sager, Z., Sanders, J., Schaefer, K., Sholevar, R., Summer, L., Tulsky, J. A., Waliji-Banglawala, A., Yudilevich-Espinoza, S.

This open-label pilot trial (n=10) found that psilocybin-assisted therapy (25mg) delivered to terminally ill home hospice patients was feasible and safe, significantly reducing demoralisation scores at week 3, though the emotional intensity of the intervention affected acceptability for some participants.

Fejer, G., Fiacchino, D., Hommel, B., Marschall, J., Prochazkova, L., Rifkin, B. D., Schoen, N., van Elk, M.

This meta-analysis (n=175) of three double-blind placebo-controlled longitudinal experiments investigated the effects of microdosing psilocybin (0.74 -; 1.71mg) on creativity and found that it increased the originality of their ideas while generating novel applications for ordinary things (divergent thinking). However, it did not increase the number of novel ideas, or their ability to detect features that are common across multiple things (convergent thinking).

Bola, M., Domagalik, A., Orłowski, P.

This cross-sectional fMRI study (n=67) found that experienced psychedelic users (≥10 lifetime experiences) showed faster and more accurate recognition of angry facial expressions alongside diminished neural responses to anger in limbic and salience network regions, enhanced responses to happiness in parietal and sensorimotor areas, and reduced emotional differentiation in default mode network regions compared to non-users.

Hommel, B., Kuchař, M., Lippelt, D. P., Marschall, J., Prochazkova, L., Schon, N. R.

This set of two randomised, double-blind, placebo-controlled trials (n=141) investigated the longitudinal effects of microdosing psilocybin truffles on cognition and well-being in semi-naturalistic settings. Contrary to anecdotal reports, the study finds no significant improvements in cognitive control, memory, social cognition, or subjective well-being compared with placebo.

Austin, E. W., Borghans, L. G. J. M., Christian, E. P., Dvorak, D., Hughes, Z. A., Jacobs, G., Juachon, M. J., Klein, A. K., Krol, F. J., Kruegel, A. C., Leong, W., Makai-Bölöni, S., Marek, G. J., Otto, M. E., Raines, S., Sporn, J., Umbricht, D., van der Graaf, A. J., Winters, J.

This Phase I single-ascending dose, randomised, placebo-controlled, double-blind study (n=48) found that GM-2505, a novel 5-HT2A receptor agonist, demonstrated an acceptable safety profile with mild transient adverse events at intravenous doses up to 20 mg, a half-life of 40-50 minutes, and dose-dependent effects on neuroendocrine hormones, neuropsychological measures, and resting-state electroencephalography similar to other 5-HT2A receptor agonists but with a duration of effects shorter than psilocybin and longer than DMT.

Agrawal, M., Chytil, M., Engel, S., Gillie, D., Mungenast, A., Olson, D. E., Rasmussen, K., Salinas, E., Wu, M. C.

This rat study found that zalsupindole (third-generation psychedelic) produced robust effects on structural and functional neuroplasticity in the prefrontal cortex as well as sustained antidepressant-like responses comparable to or greater than those of ketamine, psilocybin, and DMT, despite lacking any of the acute cellular and behavioural characteristics of hallucinogenic or dissociative compounds.

Agrawal, M., Beaussant, Y., Guérin, B., Ljuslin, M., Miner, S., Nigam, K. B., Roddy, K., Sager, Z., Sanders, J. J., Sholevar, R., Tarbi, E., Tulsky, J.

This qualitative study (n=28 interviews) of participants in a psilocybin-assisted therapy trial for cancer-related depression found that therapeutic benefits were closely tied to participants' ability to surrender (accepting and remaining open to the experience's intensity and unpredictability), with a safe, supportive, and ethical environment critical to fostering trust and engagement, and preparation and integration key to maximizing benefit, whilst music played a significant but variable role and ceremonial elements added meaning for many despite the clinical setting providing safety.

Beliveau, V., Fisher, P. M., Geisler, M., Johansen, A., Lehel, S., Lund, A., Madsen, M. K., McCulloch, D. E-W., Messel, C., Nasser, A., Ozenne, B., Plavén-Sigray, P., Søndergaard, A., Stenbæk, D. S., Svarer, C., Vassilieva, A.

This pre-print double-blind placebo-controlled trial (n=15) found that healthy participants who had a psilocybin-induced psychedelic experience in a therapeutic-like room exhibited more intense mystical-type experiences, longer-lasting psychological benefits, and greater increases in synaptic density than those dosed inside an MRI scanner, indicating that psilocybin's neuroplastic effects are modulated by environmental context.

Bershad, A. K., de Wit, H., Deutch, A. Y., Haggarty, C. J., Hill, M. N., Mayo, L. M., Petrie, S. R.

This within-subject, double-blind study (n=22) found that acute administration of methamphetamine (14 mg/70 kg) significantly lowered plasma 2-arachidonoylglycerol concentrations compared to placebo at 150-180 minutes post-administration, whilst MDMA (100 mg) did not affect endocannabinoid levels, and higher anandamide concentrations during the placebo condition correlated with disliking the 'drug effects'.

Carter, O., Castle, D., Iyer, R., Johansen, L., Liknaitzky, P., Meikle, S., Rossell, S. L., Strauss, N.

This open-label pilot trial (n=7) of psilocybin-assisted therapy (2x25mg sessions with preparatory and integration psychotherapy) for treatment-resistant depression found clinically meaningful aggregate reductions in depressive symptoms at 3 weeks (mean change=-7.14; Hedges' g=-1.27) maintained at 20 weeks. Exploratory analyses identified pre-dosing mindset, spiritual experiences, and perceptual shifts, but not expectations, as potential predictors of response, with no serious adverse events.

Avram, M., Egger, K., Meling, D., Polat, F., Scheidegger, M., Seifritz, E.

This secondary analysis of an RCT fMRI study (n=40) of meditation practitioners during a 3-day retreat found that DMT-harmine ('pharmahuasca', 120mg/120mg buccal) increased functional connectivity within the visual network and between visual and attention networks, whilst meditation alone reduced between-network connectivity, with no evidence of prolonged cortical gradient disruption characteristic of acute psychedelic effects, suggesting distinct neural mechanisms for meditation versus psychedelic-augmented meditation.

Avedisian, I., Eckert, A., Erne, L., Liechti, M. E., Luethi, D., Noorshams, D., Rudin, D., Straumann, I., Vizeli, P., Vukalovic, I.

This double-blind, placebo-controlled, crossover trial (n=23) compared equimolar doses of MDMA (100mg), MDA (92mg), and their lysine-conjugated prodrugs, finding MDA produced stronger, longer-lasting effects (6.1 vs 4.1 hours) with more psychedelic-like perceptions and adverse effects than MDMA, whilst Lys-MDA successfully delayed onset and peak effects, but Lys-MDMA failed to release MDMA and showed no effects.

Albert, S., Bedi, G., Brett, J., Day, R. O., Ezard, N., Knock, E., Liknaitzky, P., Ross, M., Siefried, K. J.

This open-label pilot study (n=15) found that outpatient psilocybin-assisted psychotherapy (25mg) with motivational enhancement and acceptance and commitment therapy for methamphetamine use disorder was safe and feasible, with participants showing reduced methamphetamine use from a median of 12 days at screening to 0 days at day 28 and 2 days at day 90 post-treatment.

Byrne, K., Garland, E. L., Hendrick, J., Lewis, B. R., Odette, M., Wu, C.

This randomised controlled trial (n=25) evaluates the safety and efficacy of psilocybin-assisted psychotherapy (25mg; PAP/PAT) combined with mindfulness-based stress reduction (MBSR) for frontline healthcare providers with depression and burnout during the COVID-19 pandemic. Results show greater improvements in depression (QIDS-SR-16), burnout (MBI-HSS-MP), demoralization (DS-II), and connectedness (WCS) in the MBSR+PAP group compared to MBSR alone, with no serious adverse events reported.

de Wit, H., Lyubomirsky, S., Martinez, R. L., Molla, H. M., Radošić, N.

This double-blind placebo-controlled study (study 1: n=15, study 2: n=20) found that MDMA (100mg) significantly increased global trust in community and society after conversation compared to placebo, whilst methamphetamine (20mg) showed no effects on subjective well-being or social connection measures.

Atasoy, S., Carhart-Harris, R. L., Deco, G., Kringelbach, M. L., Luppi, A. I., Timmermann, C., Vohryzek, J.

This neuroscience secondary (n=25) of two earlier studies used connectome harmonic decomposition to analyse how DMT affects brain function across the structural connectome (white matter pathways), finding that DMT reshapes the connectome harmonic repertoire and increases repertoire entropy similarly to other psychedelics (psilocybin, LSD, ketamine), and importantly demonstrating for the first time that energy spectrum differences and repertoire entropy measures correlate with subjective experience intensity in a time-resolved manner, revealing close coupling between connectome harmonics and conscious experience under psychedelics.

Ahmed, M., Bowrey, H. E., Brown, B., Cabrera, P., Doherty, T., Himedan, M., Kern, D. M., Lim, L., Lopena, O., Naranjo, R. R., Nuamah, I., Sanacora, G., Sarayani, A., Turkoz, I.

This real-world safety analysis of esketamine in the United States (n=58,483 patients, 1,486,213 treatment sessions over 58 months) found that sedation, dissociation, and increased blood pressure occurred in 34.7%, 41.0%, and 0.9% of sessions respectively, with serious adverse events in <0.1-0.18% of sessions, suicide rates lower than background rates, and 210 cases of abuse/misuse reported, confirming the established safety profile with no new safety signals identified.

Bonnelle, V., Cavarra, M., Feilding, A., Hutten, N. P. W., Kuypers, K. P. C., Liechti, M. E., Mason, N. L., Ramaekers, J. G., Schepers, J., Theunissen, E. L.

This randomised, placebo-controlled study (n=48) examining LSD microdosing (15 μg) for analgesia in healthy participants found no significant pain-relieving effects on pain tolerance or subjective pain perception using the Cold Pressor Task. LSD increased blood pressure, which correlated with pain tolerance, and post-hoc analysis in participants without ceiling effects suggested marginal improvements in pain tolerance and reduced unpleasantness only after the first dose, indicating that 15 μg may be below the threshold for consistent analgesic effects.

Barrow, R., Conant, C., Fava, M. F., Foster, E., Freedman, J. M., Jacobsen, P. L., Jemisen, J., Karas, S. M., Karlin, D. R., Robison, R., Solomon, T. M., Wernli, M. H.

This Phase IIb randomised, double-blind, placebo-controlled trial (n=198) found that single doses of 100 µg and 200 µg of MM120 (lysergide D-tartrate) significantly reduced anxiety symptoms at 4 weeks in adults with moderate to severe generalised anxiety disorder (GAD), with dose-dependent effects and adverse events including visual perceptual changes, nausea, and headache.

Andión, O., Farré, M., González, D., Haro, J. M., Javkin, J., Neimeyer, R. A., Sabucedo, P., Soto-Angona, Ó.

This three-arm open-label study (n=84) found that ayahuasca-assisted meaning reconstruction therapy (A-MR) produced significantly greater reductions in severe grief compared to meaning reconstruction therapy alone (d=0.86) or no treatment (d=1.07), with the A-MR group showing the largest effect size (d=2.44) and additional improvements in prolonged grief symptoms, post-traumatic growth, and quality of life.

Agrawal, M., Das, S., Goodwin, G. M., McGowan, N. M., Modlin, N. L., Rucker, J. J., Simmons, H., Tofil-Kaluza, A., Yehuda, R.

This Phase II, nonrandomised open-label trial (n=22) tested a single 25 mg dose of psilocybin with psychological support in adults with PTSD. It found the treatment to be safe and well-tolerated, with common side effects such as headache, nausea, crying, and fatigue resolving quickly. Clinically meaningful reductions in PTSD symptoms were observed at weeks 4 and 12, alongside improvements in functioning and quality of life.

Avancena, A. L. V., Kahn, J. G., Marseille, E., Vuong, L.

This cost-effectiveness analysis found that psilocybin-assisted therapy (PAT) for treatment-resistant depression (TRD) may offer economic value at $5,000 or less per treatment course, yielding an incremental cost-effectiveness ratio of $117,517 per QALY gained over 12 months, with cost-effectiveness highly sensitive to treatment price (95% probability at $3,000 vs 1% at $10,000).

Calderon, J. R., Effinger, D. P., King, J. L., Kopecky, B. J., McCorvy, J. D., O'Connell, C. K., Schalk, S. S., Thompson, S. M., Wallingford, J. R.

This pre-clinical mouse study tested chronic administration of serotonin, d-fenfluramine, or subhallucinogenic doses of LSD on cardiovascular health. Serotonin and d-fenfluramine caused ventricular thickening and valve regurgitation, respectively, while LSD produced no significant ventricular or valvular changes. Receptor binding assays showed LSD, psilocybin, and norfenfluramine had similar affinity for 5-HT2B, but LSD’s activation was short-lived, providing no evidence of heart remodeling with prolonged low-dose LSD.

Chernoloz, O., Marseille, E., Orlov, O.

This decision analysis model study (n=1000 simulated PTSD patients) evaluates the cost-effectiveness of group MDMA-assisted therapy with supplemental individual therapy for PTSD in Ukraine. It finds treatment costs $1.1M, averts 19.2 deaths, and gains 717 QALYs over 3 years, with an incremental cost-effectiveness ratio of $1537 per QALY. From a societal perspective, the intervention generates $2.6M in net savings, and scaling to 50% of eligible patients over 10 years could save 48,000 lives and gain 1.5M QALYs.

Arruda Sanchez, T., Fernandes Jr, O., Rego Ramos, L.

This case-control fMRI study (n=38 males) found that long-term ayahuasca users showed significantly higher psychological resilience scores and altered emotional brain reactivity patterns compared to controls. Machine learning algorithms achieved 75% accuracy in distinguishing users from non-users.

Aicher, H. D., Calzaferri, L., Dornbierer, D. A., Jelusic, A., Mueller, M. J., Scheidegger, M., Singer, B., Springfeld, P., Suay, D.

This secondary analysis of an RCT (n=30) found that a DMT/harmine combination (pharmahuasca) significantly impaired convergent thinking while showing trend-level reductions in divergent thinking fluency and elaboration. It also uniquely disrupted creative process transitions from incubation to illumination during a real-world painting task, suggesting that psychedelics alter creative pathways rather than uniformly enhance creativity.

Bonomo, Y. A., Collins, L., Dwyer, J., Norman, A. F., Perkins, D., Ross, M., Sarris, J.

This open-label exploratory study (n=9) tested three Acacia-based ayahuasca-like formulations in healthy volunteers with prior ayahuasca experience. In a cross-over design, two formulations (1 mg/kg DMT + 4 mg/kg harmalas) were given to five adults, while a third (ACL-010) was given to four adults at two dosages. All formulations were safe and well-tolerated, with no serious adverse events. Subjective experiences were similar to traditional ayahuasca, and ACL-010 was rated as comparable or more beneficial.

Boughey, M., Dwyer, J., Hiscock, R., Iyer, R., O’Callaghan, C., Ross, M., Williams, M. L.

This double-blind placebo-controlled trial (n=35) found that psilocybin-assisted psychotherapy (25mg) significantly reduced depression and anxiety symptoms in adults with life-threatening illnesses compared to an active placebo (100mg niacin), with benefits sustained at 26 weeks and improvements in spiritual well-being, quality of life, demoralisation, and death anxiety.

Blest-Hopley, G., Carhart-Harris, R. L., Emmanuel, O., Erritzoe, D., Kettner, H., Pasculli, G., Pate, K. M., Roseman, L., Ruffell, S. G. D., Tsang, WF.

This open-label retreat study (n=21) of veterans with traumatic brain injuries tested dried psilocybin mushrooms (1.5-5g) in two ceremonies over six days. Four weeks later, PTSD, depression, and anxiety scores fell by 50%, 65%, and 28% respectively, while EEG showed reduced delta/theta power and increased alpha/beta coherence, suggesting improved emotional regulation and cognition.

Aarrestad, I. K., Barragan, E. V., Cameron, L. P., Casey, A. B., Chytil, M., Fenton, E. M., Ghandi, S. P., Gray, J. A., Guanzon, N., Hansen, H. D., Heifets, B. D., Hempel, C., Hennesssey, J. J., Hu, H., Johnson, S. B., Kim, C. K., Knudsen, G. M., Liston, C., Lozano, S. A., Ly, C., Madsen, C. A., McCorvy, J. D., Meyer, R., Muir, J., Nord, A. S., Olson, D. E., Olson, E., Patel, S. D., Powell, N. A., Quon, G., Rasmussen, K., Redd, C., Rijsketic, D. R., Rose, D., Sambyal, R., Seban, N., Viswanathan, J., Wheeler, D. G.

This rodent study found that the nonhallucinogenic psychoplastogen tabernanthalog (TBG) promotes cortical neuroplasticity and sustained antidepressant effects through the same 5-HT2A, TrkB, mTOR, and AMPA receptor pathway as psychedelics, but without inducing the immediate glutamate burst or immediate early gene activation previously thought necessary for psychedelic-induced neuroplasticity.

Hawrot, T., Mueller, F., Schmid, Y.

This review (2025) of the Swiss limited access scheme describes how approximately 100 physicians treated 723 patients with MDMA, LSD, or psilocybin in 2024, with patients typically receiving 2-4 psychedelic-assisted therapy sessions within 12 months for treatment-resistant conditions.

Hieronymus, F., López, E., Lundberg, J., Sjögren, H. W.

This meta-analysis of 17 trials (n=4,960) comparing control treatment outcomes across depression studies found that participants receiving control treatments in psilocybin trials showed significantly less improvement than those in SSRI or esketamine trials, with control response rates 14-23% lower, suggesting that psilocybin's reported antidepressant efficacy may be overestimated compared to conventional treatments despite having similar active treatment effects and lower dropout rates.

Belahda, D., Graux, C., Igounenc, N., Luquiens, A., Mura, T., Rochefort, P., Sergent, F., Serrand, C.

This double-blind, randomised controlled pilot study (n=30) found that psilocybin-assisted psychotherapy psilocybin (25mg; 2x; n=20) showed significantly higher abstinence rates at 12 weeks (55% vs 11%) compared to placebo (1mg; n=10) in patients with severe alcohol use disorder (AUD) and depression (MDD) who had recently completed detoxification.

Buchanan, D., Chaiken, A., Cherian, K. N., Espil, F., Keller, C. J., Keynan, J. N., Lissemore, J. I., Rolle, C. E., Saggar, M., Sridhar, M., Williams, N. R.

This analysis of an open-label observational study (n=30) found that magnesium-ibogaine therapy in combat veterans with traumatic brain injury (TBI) led to slower brain wave patterns and reduced neural complexity on EEG, which correlated with improvements in PTSD, anxiety, and cognitive function at one-month follow-up.

Carhart-Harris, R. L., Deco, G., Erritzoe, D., Kringelbach, M. L., Nutt, D. J., Sanz Perl, Y., Socoró-Garrigosa, M., Vohryzek, J.

This computational brain modelling study (n=42) compared how psilocybin (25mg; 2x) and escitalopram treatments affect brain hierarchy and neural plasticity in depressed patients. It found that psilocybin increased brain susceptibility to change while escitalopram reduced it, though both treatments promoted transitions towards healthier brain states.

Alexander, R., Bryson, N., Hirman, J., Hocevar-Trnka, J., Johnson, M. W., Ludbrook, G., Morrish, G., Pollack, M., Taylor, B.

This double-blind, randomised, placebo-controlled Phase I study (n=48) evaluates the safety, pharmacokinetics, and psychoactive effects of RE104 (psilocybin analog; Luvesilocin; a prodrug of 4-OH-DiPT) in healthy adults with prior psychedelic experience. RE104 was well tolerated up to 40 mg with no serious adverse events, and plasma levels of its active form correlated with subjective drug effect and mystical experience scores. The compound produced psilocybin-like effects with a shorter duration (3-4 hours), supporting further therapeutic investigation.

DeLeon, C., DiBerto, J. F., Dror, R. O., Fay, J. F., Gloriam, D. E., Gumpper, R. H., Hauser, A. S., Huang, X.-P., Jain, M. K., Keiser, M., Kim, K., Krumm, B. E., Madsen, J. S., Nichols, D. E., Roth, B. L., Schmitz, G. P., Shoichet, B. K., Shub, L., Slocum, S. T., Suomivuori, C-M., Tummino, T. A.

This receptor profiling study (n=41 compounds) maps the pharmacological activity of classical psychedelics across 318 human G-protein-coupled receptors and, for LSD, over 450 human kinases. It finds that psychedelics act potently at nearly all serotonin, dopamine, and adrenergic receptors, with multiple 5-HT2A receptor signalling pathways linked to psychedelic effects in vivo.

Albarracín, S. G., Bistue Millón, M. B., Bruno, D., Bruno, M. A., Díaz-Dellavalle, P., Diez, P., Feresin, G. E., Garcés, M. A., Kassuha, D. E., Noguera, L., Orosco, L., Ortiz, J. E., Vita, L., Zanino, M.

This Phase I clinical trial (n=36) of sublingual 5-MeO-DMT (6-12 mg weekly doses over four weeks) in adults with moderate to high anxiety/depression demonstrated good safety and tolerability with no significant adverse events, rapid absorption with peak plasma concentrations at 20 minutes, dose-dependent neurophysiological modulation without full psychedelic effects, and maintenance of normal cognitive and behavioral function.

Becker, A. M., Klaiber, A., Ley, L., Liechti, M. E., Luethi, D., Mueller, L., Schmid, Y., Thomann, J.

This pharmacokinetic-pharmacodynamic analysis (n=46) of two Phase I trials of oral mescaline (100-800 mg) showed dose-proportional exposure with peak concentrations at 2 hours, a half-life of 3.5 hours, onset of effects around 1 hour post-dose, maximum effect intensity and duration ranging from 13% and 2.8 hours (100 mg) to 89% and 15 hours (800 mg), with 53% urinary excretion unchanged and 31% as the main metabolite, indicating at least 53% oral bioavailability.

Andreassen, O. A., Autran, I., Berthold-Losleben, M., Clausen, I., Goksøyr, I. W., Holst, R., Jentoft van de Vooren, I.-T., Kvam, T-M., Mørch-Johnsen, L., Rog, J., Stewart, L. H.

This open-label pilot study (n=12) found that MDMA-assisted therapy (80-120mg; 2x) significantly reduced depression scores (MADRS) by 19.3 points and functional impairment (-11.7) in participants with moderate to severe major depressive disorder (MDD), with no serious adverse events reported over 8 weeks following treatment.

Bruno, N., Cavanna, F., D'Amelio, T., de la Fuente, L. A., Muller, S., Pallavicini, C., Tagliazucchi, E.

This double-blind study (n=23) using eye-tracking found that high doses of psilocybin mushrooms (0.5-3g dried) caused more localised visual exploration of paintings and less entropic fixation patterns compared to low doses, while increasing subjective emotional intensity without affecting aesthetic ratings of the artworks.

Goldberg, S. B., Hendricks, P. S., Osika, W., Simonsson, O., Swords, C. M.

This longitudinal observational study (n=12,345) of U.S. residents found that naturalistic psychedelic use (n=505, 4.1% of participants) was associated with modest increases in depressive symptoms, particularly when occurring in 'risk contexts' characterised by negative mindset and lack of psychological support, with challenging psychedelic experiences mediating this relationship and suggesting that unsupervised psychedelic use may not be generally therapeutic and could worsen depression under certain circumstances.

Äbelö, A., Ashton, M., Dornbierer, D. A., Egger, K., Scheidegger, M., Smallridge, J. W., van Rotz, R.

This secondary of a single-blind, randomised study (n=16) using DMT (0-120mg) with harmine (0-180mg) in an ayahuasca-inspired (‘pharmahuasca’) formulation found that harmine significantly enhanced DMT bioavailability and prolonged absorption, resulting in higher sustained plasma concentrations and increased subjective psychedelic effects, with population pharmacokinetic/pharmacodynamic modeling revealing substantial interindividual variability in clearance, bioavailability, and sensitivity to psychedelic effects.

Coarfa, C., Hecker, L., Kato, K., Kleinhenz, J. M., Shin, Y.-J., Zarrabi, A. J.

This mouse study (n=58) provides the first experimental evidence that psilocin extends cellular lifespan and that psilocybin promotes increased longevity in aged mice. The findings suggest psilocybin may have geroprotective potential, though the molecular mechanisms remain unclear.

Bradley, E. R., Downey, A. E., Fernandes-Osterhold, G., Fredenburg, L., Gard, D. E., Krystal, J. H., Llerena, K., Nerayo, J., Nielsen, B., O'Donovan, A., Sakai, K., Szigeti, B., Woolley, J. D.

This pre-print open-label trial (n=14) administered psilocybin (10-25mg) plus psychotherapy to people with bipolar II depression. It was well tolerated (only transient cardio spikes, mild anxiety/nausea/headache, and three temporary hypomania-or-suicidality events) and cut MADRS scores by 13-19 points at 21 days and 14 points at 90 days while boosting quality of life, with no excess mania or psychosis.

Adams, M., Blest-Hopley, G., Busch, C., Calnan, M., Carhart-Harris, R. L., Kettner, H., Piper, T., Roseman, L., Ruffell, S. G. D.

This observational retreat study (n=58) of military veterans attending psilocybin (n=13) or ayahuasca (n=45) retreats found significant improvements across all eight measured domains four weeks later, with the largest percentage reductions in depression (PHQ-9, 29%) and PTSD symptoms (PCL-5, 26%). Psilocybin outperformed ayahuasca on seven outcomes (ayahuasca led slightly on PTSD), men improved more than women on most scales, and greater baseline severity predicted larger post-retreat gains.

Canuso, C. M., Drevets, W. C., Fu, D. J., Janik, A., Lane, R., Macaluso, M., Mattingly, G. W., Popova, V., Qiu, X., Shelton, R. C., Zajecka, J. M.

This Phase IV randomised controlled trial (n=378) found that esketamine nasal spray (Spravato) monotherapy at both 56mg and 84mg doses significantly reduced depression scores compared to placebo in treatment-resistant depression (TRD) patients at 28 days, with rapid onset of effect observed within 24 hours and moderate effect sizes of 0.48 and 0.63 respectively.

Blainey, M. G., Brudner, R. M., Doyle, Z., Kaczmarek, E., Lipsitz, O., McIntyre, R. S., Meshkat, S., Offman, H., Rosenblat, J. D., Schulz-Quach, C., Sethi, R., Weiglein, G.

This secondary analysis of treatment-resistant depression patients (n=31) with major depressive disorder or bipolar II disorder found that greater mystical experiences during the first 25mg psilocybin dose predicted better antidepressant outcomes, though this relationship was not observed for subsequent doses.

Carhart-Harris, R. L., Erritzoe, D., Fineberg, N. A., Godfrey, K., Healy, C. J., Lee, H., Nutt, D. J., O'Connor, S., Peill, J. M., Pellegrini, L., Pereira De Souza, A. M. F. L., Reed, S., Robbins, T. W., Rohani-Shukla, C.

This open-label study (n=19) found that 10mg oral psilocybin produced a significant reduction in OCD symptoms compared to 1mg, with a large effect size (Cohen's d = 0.82) one week after dosing, particularly for compulsions rather than obsessions, though effects diminished over subsequent weeks.

Amaro, H., Cole, S. P., Jain, R., Jain, S., Moller, A. C., Penn, A. D., Raison, C. L., Teixeira, P. J.

This cross-sectional study (n=2,510) of US adults with psychedelic experience found that participants retrospectively reported widespread improvements in health behaviours including reduced alcohol (66%) and tobacco (49%) use, better dietary habits (49%), and decreased impulsivity (48-72%), with microdosers and frequent users showing greater positive changes.

Böge, K., Gabriel, T., Kaiser, S., Kirschner, M., Monari, S., Preller, K. H., Sabé, M., Scheuerlein, L., Sentissi, O., Seragnoli, F., Solmi, M., Sulstarova, A.

This systematic review (n=93 cases) found that psychedelic-induced psychosis, primarily caused by LSD and MDMA, lasted an average of 1.8 weeks and responded much better to second-generation antipsychotics (91% response rate) than first-generation antipsychotics (27% response rate), though one-third of patients later developed schizophrenia spectrum disorders.

Carhart-Harris, R. L., Erritzoe, D., Giribaldi, B., Henry, J., Lyons, T., Nutt, D. J.

This secondary analysis of an RCT comparing psilocybin therapy to escitalopram in MDD patients (n=59) found that psilocybin produced superior improvements in cognitive biases. Psilocybin significantly increased self-reported optimism (d=1.1) and optimistic beliefs about desirable life events (d=1.1), while improving all three domains of dysfunctional attitudes (achievement, dependency, and self-control). Escitalopram showed more modest effects, reducing pessimism about negative events and improving only the achievement domain of dysfunctional attitudes.

Aicher, H. D., Dornbierer, D. A., Meling, D., Mueller, M. J., Scheidegger, M., Wicki, I.

This secondary analysis of a randomised, double-blind, placebo-controlled trial (n=31) demonstrated that an ayahuasca-inspired DMT/harmine formulation significantly enhanced mindfulness and compassion (both self-compassion and compassion for others) one day post-treatment, with more pronounced effects in high-sensitivity participants.

Andersen, T. L., Falck, N., Fisher, P. M., Geisler, M., Holze, F., Jensen, P. S., Johansen, A., Johansen, S. S., Knudsen, G. M., Larsen, K., McCulloch, D. E-W., Neufeld, V., Nielsen, M. K. K., Nykjær, C. H., Randrup, P. P., Reveles Jensen, K. H., Shulganov, V., Skov-Andersen, P., Spanggård, A., Steenstrup, E., Stenbæk, D. S., Svarer, C.

This pre-print simultaneous PET-MRI study (first of its kind) demonstrates that LSD increases global cerebral blood flow and internal carotid artery flow without affecting artery diameter (opposite to psilocybin's effects), while decreasing global connectivity (particularly in visual networks) and increasing network entropy and spatial complexity, with researchers also observing an anticlockwise hysteresis loop (dynamic lag between an input and an output) between plasma levels and subjective effects that challenges existing hypotheses about psychedelic mechanisms of action.

Aires, R., Almeida, R., Araújo, D. B., Arichelle, F., Barros, H., Bolcont, R., da Costa Bezerra, R. B., Dantas Correa, L., de Araujo Costa Neto, L. A., Falchi-Carvalho, M., Galvão-Coelho, N. L., Laborde, S., Lima de Queiroz, M. V. J., Medina, M., Nunes Ferreira, L. F., Palhano-Fontes, F., Pantrigo, E. J., Ruschi Silva, S., Silva-Costa, N., Thie, K., Wießner, I.

This first RCT (n=25) of vaporised DMT (60mg) demonstrated that DMT significantly increased subjective experience measures while causing only transient, safe physiological changes and predominantly mild adverse events. This suggests that inhaled DMT is safe, well-tolerated, and effective at inducing profound altered states of consciousness. Significant correlations were observed between physiological responses and subjective experiences.

Andrashko, V., Androvičová, R., Balíková, M., Bravermanová, A., Brunovský, M., Hájková, K., Horáček, J., Klučková, T., Korčák, J., Kuchař, M., Nikolič, M., Páleníček, T., Tylš, F., Vejmola, C., Viktorin, V., Viktorinová, M., Zach, P.

This double-blind, placebo-controlled, cross-over study (n=40) found that two doses of psilocybin (18.2mg/70kg) administered at least 56 days apart (avg. 15 months) produced positive lasting effects in healthy individuals regardless of previous psychedelic experience, sex, or setting, with challenging experiences in controlled environments not causing adverse outcomes, supporting psilocybin's psychological safety for repeated use.

Agrawal, M., Emanuel, E., Jenkins, B., Leeks, C., Roddy, K.

This Phase II trial long-term follow-up (n=30) found that a single dose of psilocybin (25mg) combined with psychological support provided sustained benefits for cancer patients with depression, with 54% showing significant depression reduction (50% remission) and 46% experiencing reduced anxiety at 2 years' follow-up, suggesting a potential paradigm shift in depression treatment for cancer patients compared to traditional daily antidepressants.

Aboulafia-Brakha, T., Alaux, S., Amberger, C., Buchard, A., Cazorla, L., Furtado, L., Mabilais, C., Penzenstadler, L., Thorens, G., Zullino, D.

This pre-print reports an observational pilot study (n=12) examining salivary oxytocin ('love/bonding hormone') dynamics during LSD-assisted psychotherapy (100-150μg) for treatment-resistant depression (TRD), finding significant time-dependent variations in both oxytocin levels and subjective drug intensity ratings, suggesting oxytocin may serve as a potential biomarker for psychedelic therapy.

Barnett, H., Szigeti, B., Williams, Z. J.

This pre-print pre-registered meta-analysis (s=24) comparing psychedelic-assisted therapy (PAT) and open-label traditional antidepressants (tAD) for major depression found no significant difference in effectiveness between the two approaches, with both producing clinically meaningful improvements, challenging previous assumptions about PAT's superiority when accounting for the unblinding effect present in psychedelic trials.

Aaronson, S. T., Bostian, C., Conlan, E., Donnelly, A., Eisen, K., Ellis, S. P., Feng, W., Lean, M., Ostacher, M., Suppes, T.

This open-label follow-up study (n=10) of Veterans with severe treatment-resistant depression (TRD) found that a single dose of psilocybin (25mg) significantly reduced depression for up to 12 months, though effects began to wane after 6 months, with 40% maintaining response and 30% maintaining remission at the 12-month follow-up.

Bowrey, H. E., Clemens, K., Desai, U., Doran, J., Eid, D., Joshi, K., Kirson, N., Qu, A., Rive, B., Teeple, A.

This economic analysis comparing esketamine nasal spray (plus oral antidepressant) versus quetiapine extended release (plus oral antidepressant) for treatment-resistant depression (TRD) found esketamine achieved higher remission rates at 32 weeks (50% vs 33%) and lower cost-per-remitter in both commercial ($3,102 lower) and Medicaid ($456 lower) settings, with even greater cost savings in scenarios where non-responders received transcranial magnetic stimulation.

Auernig, M., Becker, A. M., Boehlke, C., Borgwardt, S., Kohut, J., Ley, L., Liechti, M. E., Loh, N., Müller, F., Santos de Jesus, J., Zaczek, H.

This double-blind controlled trial (n=61) found that high-dose LSD-assisted therapy (100μg + 200μg) reduced depression symptoms more than low-dose LSD (25μg + 25μg) in patients with moderate-to-severe major depressive disorder (MDD), with benefits lasting up to 12 weeks and similar side effects between groups.

Carhart-Harris, R. L., Erritzoe, D., Giribaldi, B., Kettner, H., Lyons, T., Nutt, D. J., Peill, J. M., Roseby, W., Roseman, L., Spriggs, M. J.

This mixed-methods analysis (n=973 across multiple cohorts) examines how psychedelic experiences influence “meaning in life” using the Meaning in Life Questionnaire (MLQ) across three contexts: a psilocybin clinical trial for depression, a single-arm healthy volunteer study, and a naturalistic retreat-based study. It finds strong increases in the “presence of meaning” subscale and modest decreases in “search for meaning,” with enhancements linked to improvements in mental health and to the intensity of mystical, ego-dissolution, and emotional breakthrough experiences.

Chacko, R., Dosenbach, N. U. F., Flavin, K., Horan, C., Laumann, T. O., Lenze, E. J., Metcalf, N., Nicol, G., Perry, D., Renau, T. R., Schweiger, J., Siegel, J. S., Snyder, A. Z., Subramanian, S.

This randomised, cross-over study (n=7) used precision functional mapping with high-resolution multi-echo fMRI to characterise psilocybin (25mg) versus methylphenidate effects on brain networks, revealing decreased network modularity during psilocybin exposure and reproducible network changes. Participants showed unique brain configurations and reported stronger mystical experiences with psilocybin compared to methylphenidate.

Arrigo, E., Damiani, S., Doose, A,, Fusar-Poli, P., La-Torraca-Vittori, P., Lanterna, S., Palesi, F., Pischedda, D., Ricca, V., Tarchi, L., Tosi, E.

This analysis of fMRI data (n=15) examined how LSD (75μg) affects local brain activity and connectivity, finding that LSD decreased both measures in somatosensory/visual areas, with additional activity decreases in Default Mode and Fronto-Parietal networks and connectivity decreases in subcortical regions, with these changes occurring primarily in brain regions with high densities of D2 and 5HT1a receptors, suggesting complex neurobiological mechanisms underlying LSD's effects.

Greenway, K. T., Pronovost-Morgan, C., Roseman, L.

This Delphi consensus study (n=89) involved psychedelic researchers, clinicians, and past trial participants across 17 countries to develop reporting standards for extra-pharmacological variables in psychedelic clinical trials. It resulted in the ReSPCT guidelines, a 30-item framework covering physical environment, session procedures, therapeutic protocol, and subjective experiences, aiming to standardise how “set and setting” are documented in future research.

Mason, N. L., Ramaekers, J. G., Reckweg, J., Svendsen, C. B., Terwey, T. H., Theunissen, E. L.

This data analysis of three studies (n=84) validates a three-item Peak Experience Scale (PES) for rapidly assessing 5-MeO-DMT experiences, demonstrating that the scale shows strong internal consistency (Cronbach's α=0.896), correlates highly with established psychedelic experience measures (MEQ-30, EDI, 5D-ASC), and could effectively guide dosing regimens for rapid-acting psychedelics.

Atila, C., Camerin, S.-J., Christ-Crain, M., Liechti, M. E.

This secondary analysis of an RCT (n=15) investigates the acute effects of MDMA (100mg) on anterior pituitary function in healthy adults. It finds that MDMA significantly activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing both ACTH and cortisol levels. No significant effects were observed on other anterior pituitary hormones, though prolactin showed a mild, non-significant increase.

Bossis, A. P., Griffiths, R. R., Jesse, R., Johnson, M. W., Richards, W. A., Ross, S., Sepeda, N. D.

This randomised, waitlist-controlled exploratory study (n=29) of psychedelic-naïve clergy delivered two supported psilocybin sessions (20mg/70kg followed a month later by 20-30mg/70kg). Six months after screening (and still evident 16 months later) the psilocybin group showed sustained improvements in religious practice, leadership effectiveness and overall well-being, with 96 % ranking at least one session among their five most spiritually significant life events and no serious adverse events despite 46 % describing the experience as among their five most challenging.

Barton, D., Baune, B. T., Berk, M., Chatterton, M. L., Dong, V., Faller, J., Fitzgerald, P. B., Glozier, N., Glue, P., Hackett, M., Hadzi-Pavlovic, D., Hood, S., Loo, C., Martin, D., Mihalopoulos, C., Mills, N. T., Mitchell, P. B., Perez, J., Rodgers, A., Sarma, S., Somogyi, A. A., Thai, T.

This cost-utility analysis, alongside a randomised controlled trial (n=174), compared subcutaneous ketamine (twice-weekly for 4 weeks) with midazolam in treatment-resistant depression. Including midazolam costs, ketamine raised QALYs (0.435 vs 0.352) and was dominant with an 89-91 % chance of costing < $50 000/QALY, but once these comparator costs were excluded ketamine was no longer cost-effective (ICER ≈ $108 500-$251 250/QALY, ≤ 5 % probability).

Brewerton, T. D., Finn, D. M., Fisher, H., Kaye, W. H., Kim, J., Modlin, N. L., Peck, S. K., Shao, S., Trim, J.

This case study (n=2) of an open-label pilot study (n=10) explores psilocybin-assisted psychotherapy for women with anorexia nervosa (AN or partial remission). Two participants experienced the therapeutic emergence of previously dissociated traumatic memories, leading to remission of AN symptoms and meaningful weight gain at 3-month follow-up.

Arikci, D., Holze, F., Hysek, C. M., Liechti, M. E., Luethi, D., Mueller, L., Rudin, D., Vizeli, P.

This randomised, double-blind, placebo-controlled crossover study (n=20) tests the bioequivalence and oral bioavailability of LSD base and tartrate in various formulations (ethanolic solution, watery solution, dissolvable tablet, and IV). All oral formulations were bioequivalent with 80% absolute oral bioavailability. IV LSD produced stronger subjective effects, including more ego dissolution and anxiety.

D'Angelo, S., Dempsey, M., Giombi, K., Khavjou, O., Lu, T., Tayebali, Z.

This population-level Markov simulation study (n=350,000 initial patients + 11,296 annually) models the economic impacts of intravenous ketamine versus ECT for treatment-resistant depression over 5 years. The model projects annual societal savings of $828.2 million ($95.3M to patients, $743.7M to payers) with expanded ketamine access, though with an added $10.8M annual caregiver burden.

Durant, C., Higbed, L., Morgan, C. J. A., Nutt, D. J., O'Biren, S., Sessa, B., Szigeti, B., Thurgur, H., Wilson, S.

This secondary analysis of an open-label feasibility study (n=14) of MDMA-assisted psychotherapy for alcohol use disorder (AUD) found, through Bayesian analysis, a 55-63% probability of achieving a 2-level reduction in WHO drinking risk at 3 months follow-up, with preliminary evidence suggesting reductions in alcohol craving and improvements in sleep and psychosocial functioning compared to baseline.

Bryan, C. S., de Kam, M. L., Jacobs, G. E., Otto, M. E., Stewart, N., Stillwell, C., van der Heijden, K. V., van Gerven, J. M. A., van Leuken, M. B., Zuiker, R. G. J. A.

This randomised, double-blind, placebo-controlled single ascending dose study (n=29) tested prolonged intravenous DMT administration (30-s bolus (1.5-7.5mg) + 6-h infusion (4.4-33.3nl/ml)) in healthy volunteers. It found the treatment to be safe, with only mild, self-limiting adverse events, and observed mild psychedelic effects, reduced attention and stability, and decreased occipital alpha EEG power at higher doses, supporting further investigation in stroke recovery contexts.

Ammendolia, I., Calapai, F., Calapai, G., Cardia, L., Curro, M., Esposito, E., Mannucci, C., Midiri, P., Mondello, C.

This pharmacovigilance analysis (n=751) examines suspected adverse reactions (SARs) to esketamine nasal spray (Spravato) reported in the EudraVigilance database across European countries. The study identifies increased blood pressure (15.4%) and dissociation (15%) as the most common SARs, with data suggesting a potentially higher risk of suicidality with esketamine compared to fluoxetine and venlafaxine, prompting recommendations for careful monitoring of patients with a history of suicidal ideation.

Carhart-Harris, R. L., Demetriou, L., Erritzoe, D., Ertl, N., Giribaldi, B., Nutt, D. J., Roseman, L., Wall, M.

This secondary analysis of an RCT (n=59) investigates the impact of psilocybin-assisted therapy (PAT) and escitalopram (SSRI) on responsiveness to emotional stimuli in patients with moderate-to-severe major depressive disorder over a 6-week trial period. Responses to emotional faces were reduced in the SSRI group, not the psilocybin group at the follow-up.

Agin-Liebes, G. I., Mitchell, J., Zeifman, R. J.

This secondary analysis (n=82) of a Phase III RCT of MDMA-assisted therapy found significant improvements in both uncompassionate self-responding and compassionate self-responding across all six Self-Compassion Scale subscales, most with large effect sizes. Changes in self-compassion fully mediated the reductions in PTSD severity and depressive symptoms observed with MDMA-AT versus placebo plus therapy, though no significant effects were seen for alcohol or substance use outcomes.

Chen, L. N., Doherty, T., Drevets, W. C., Fu, D. J., Lacerda, A. L. T., Lane, R., Morrison, R. L., Paik, J.-W., Popova, V., Sanacora, G., Wilkinson, S. T., Young, A. H., Zaki, N.

This Phase III open-label extension study (n=1148) evaluates the long-term safety and efficacy of esketamine nasal spray combined with oral antidepressants in treatment-resistant depression (TRD) patients who previously participated in other Phase III trials. The study involved flexible dosing of intranasal esketamine (twice-weekly during induction, then weekly to monthly during maintenance) with direct staff supervision, with participants either entering through a 4-week induction phase (n=458) or directly into maintenance (n=690) based on their previous response.

Brunovský, M., Horáček, J., Janečková, L., Kelemen, E., Korčák, J., Koudelka, V., Kuchař, M., Nekovářová, T., Nikolič, M., Páleníček, T., Šíchová, K., Syrová, K., Tesař, M., Tylš, F., Vejmola, C., Viktorin, V., Viktorinová, M.

This cross-species experimental study (n=21 humans; n=10 rats) finds that psilocin (18.2mg/70kg for humans; 0.3mg/kg for rats) impairs the ability to distinguish between static and moving images in both humans and rats. In humans, the impairment aligns with psilocin plasma levels and self-reported hallucination intensity. In rats, the effect is specific to motion perception, providing the first evidence of psilocin-induced visual distortions across species.

Aicher, H. D., Bottari, D., Caflisch, L., Dornbierer, D. A., Elsner, C., Hempe, A., Kometer, M., Meling, D., Mueller, M. J., Müller, J., Scheidegger, M., Steinhart, C., Suay, D., Wicki, I.

This secondary analysis of an RCT brain imaging (EEG) study (n=30) examines how DMT/HAR and Harmine alone affect face recognition and self-processing in healthy males using a visual oddball task. It finds DMT/HAR enhanced early visual processing while reducing neural differentiation between self and other faces at posterior sites, suggesting psychedelics reshape rather than erase self-boundaries while preserving socially meaningful representations.

Carhart-Harris, R. L., Erritzoe, D., Harding, R., Hendler, T., Nutt, D. J., Roseman, L., Singer, N., Wall, M. B.

This secondary analysis of a randomised trial (n=41) found that while psilocybin therapy (2&#215;25 mg, three weeks apart) maintained emotional responses to musical surprises and increased activation in prefrontal and sensory brain regions. Escitalopram reduced surprise-related affective responses and increased activation in memory and emotional processing areas, suggesting distinct neurological mechanisms between these treatments for depression.

Kamphuis, J., Schoevers, R. A., Smith-Apeldoorn, S. Y., Spijker, J., van der Meij, A., Veraart, J. K. E.

This real-world study (n=185) found that oral esketamine (35-210mg/70kg; 6w; 12x) was effective and well-tolerated in severely treatment-resistant depression (TRD) patients, showing significant symptom improvement with minimal dropouts (7.6%), suggesting it could be a viable alternative to intranasal or intravenous administration.

Carhart-Harris, R. L., de Wied, D., Kettner, H., Zhou, K.

This prospective cohort study (n=654 start, n=212 end) investigated delusional ideation, magical thinking, and HPPD symptoms in participants before and after planned psychedelic use. Results showed reduced delusional ideation after one month, no changes in magical thinking, and HPPD-like effects in 30% of participants (though rarely distressing at <1%), with younger age, female gender, psychiatric history, and baseline trait absorption predicting HPPD-like effects.

Black, J. C., Dart, R. C., Hunt, J., Jewell, J. S., Ladka, M. S., Monte, A. A., Nerurkar, K., Olsen, H. A., Rockhill, K. M., Sumbundu, K. B., Wolf, C.

This multi-dataset observational study (n=5 nationally representative surveys) quantifies changes in psilocybin use and healthcare utilisation in the United States between 2014 and 2023. It finds that adult lifetime use increased from 10.0% (25 million) in 2019 to 12.1% (31.3 million) in 2023, while adolescent use rose modestly from 1.1% to 1.3% during the same period.

Hong, C. J.

This multicenter, randomised, placebo-controlled clinical trial (n=236) investigates the efficacy and safety of esketamine (ESK) (8x35mg) for smoking cessation in patients with lung cancer and major depressive disorder (MDD). Eight weekly intranasal ESK sessions significantly improved both self-reported (44.1%) and biologically verified (28.8%) smoking abstinence at 6-month follow-up, alongside reductions in depression, anxiety, nicotine dependence, and respiratory symptoms.

Almeida, R., Araújo, D. B., Arcoverde, E., Arichelle, F., Barbosa, D. C., Barros, H., Bolcont, R., Costa-Macedo, J. V., da Costa Bezerra, R. B., da Cruz Nunes, J. A., Dantas Correa, L., de Araujo Costa Neto, L. A., Falchi-Carvalho, M., Florence-Vilela, R., Galvão-Coelho, N. L., Laborde, S., Macedo, R. K. A., Montanini, D., Nunes Ferreira, L. F., Palhano-Fontes, F., Pantrigo, E. J., Silva, S. R. B., Teixeira, E., Wießner, I.

This open-label fixed-order dose-escalation trial (n=14) evaluated inhaled DMT (15mg & 60mg) for treatment-resistant depression (TRD) for the first time. Results showed rapid and sustained antidepressant effects with a 21-point reduction on the Montgomery-Asberg Depression Rating Scale by day 7 (p<0.001), an 86% response rate, and a 57% remission rate lasting up to 3 months, with significant decreases in suicidal ideation (SI).

Abend, R., Karp Barnir, E., Lev-Ran, S., Mikulincer, M., Naor, L., Rubinstein, Z.

This observational study (n=343) of terrorist attack survivors found that those under the influence of classic psychedelics during the traumatic event reported lower anxiety and post-traumatic symptoms compared to MDMA users or non-users, particularly when psychedelics were taken alone.

Allocca, G., Barba, T., Carhart-Harris, R. L., Daily, Z. G., Erritzoe, D., Janeckova, S., Kloft-Heller, L., Kuchar, M., Luan, L., Mason, N. L., Ona, G., Páleníček, T., Ramaekers, J. G., Reydellet, D., Sanders, J. W., Smith, C. H., Soto-Angona, Ó., Timmermann, C., Uthaug, M. V.

This exploratory observational study (n=14) examines the phenomenological and neuronal effects of 5-MeO-DMT through micro-phenomenological interviews, psychometric questionnaires, and EEG recordings in naturalistic ceremonial settings. The findings reveal that 5-MeO-DMT induces variable experiences of visual imagery, bodily and narrative self-disruption, and reduced phenomenal distinctions, with EEG showing alpha and beta power reductions suggesting inhibited top-down processing.

Jeong, S. H., Morse, D. J., Murphy, R. J., Muthukumaraswamy, S., Sumner, R. L.

This re-analysis of a Phase I RCT (n=80) examines the pharmacokinetics (how the body affects a drug) of LSD microdosing (10µg; 14x; 6w) in healthy adult males. The study established a one-compartment pharmacokinetic model showing an elimination half-life of 3.08h, found minimal physiological effects (<15% change in heart rate), noted possible influence of CYP enzymes on drug metabolism, and reported no changes in peripheral BDNF levels.

Carhart-Harris, R. L., Eckernäs, E., Kuceyeski, A., Luppi, A. I., Roseman, L., Singleton, S. P., Timmermann, C.

This re-analysis (n=14) applies a receptor-informed network control theory framework to investigate the effects of DMT on the brain's control energy landscape. It reveals that DMT, like LSD and psilocybin, reduces global control energy, with these trajectories correlating with EEG signal diversity and subjective intensity ratings. Furthermore, the regional effects of DMT correlate with serotonin 2a receptor density, demonstrating a potential proof-of-concept for predicting pharmacological intervention effects on brain dynamics using control models.

Cameron, L. P., Casey, A. B., Gallagher, A., Gomez, A. M., Green, N., Heifets, B. D., Kheirbek, M. A., Klein, A. S., Lammel, S., Li, A., Li, R., Liu, C., Lu, O. D., Malenka, R. C., Pomrenze, M. B., Raymond, K., Shindy, L., Sohal, V., Vaillancourt, S., Wallquist, K., White, K., Zou, M.

This pre-print multi-laboratory mouse study (n=~200 mice across five sites) demonstrates that psilocybin (2mg/kg) produces robust acute effects in mice including increased anxiety-related behaviours and decreased fear expression. However, it fails to show consistent persistent therapeutic effects 24 hours after administration, suggesting previous claims about psilocybin's lasting benefits may have been overstated.

Bock, M. A., Bradley, E. R., Busby, Z., Fernandes-Osterhold, G., Finley, P. R., Llerena, K., Ludwig, C., McKernan, A., O'Donovan, A., Ostrem, J. L., Penn, A. D., Rosen, R. C., Sakai, K., Szigeti, B., Tanner, C. M., Wang, A. C. C., Woolley, J. D., Zuzuarregui, J. R. P.

This open-label pilot study (n=12) found that psilocybin therapy (10mg followed by 25mg dose with psychotherapy) for Parkinson's disease patients with depression and/or anxiety appeared safe with no serious adverse events, whilst showing promising improvements in motor symptoms, cognitive function, depression and anxiety that persisted at three-month follow-up.

Abdel, F., Ahmed, S. S., Hanson, R. W., Hell, F., Jung, R., Kinreich, S., Moore, T. M., Teed, A. R., Tung, E., Walker, K.

This observational study (n=202, 470, and 624) compares ketamine alone (KET) to ketamine combined with psychotherapy (KET+PSY) (35mg x 6) for depression and PTSD. Both treatments led to substantial symptom improvements, but no significant differences were found between groups. Exploratory analyses suggest younger females may benefit more from combined treatment, while older males may do better with ketamine alone.

Bilash, O. M., Che, A., Davoudian, P. A., Jiang, Q., Kim, H., Kwan, A. C., Liao, C., Liu, R.-J., Nothnagel, J. D., Savalia, N., Shao, L-X,, Tan, D., Wojtasiewicz, C., Woodburn, S. C.

This mouse study investigates how psilocybin affects different types of brain cells in the medial frontal cortex (mPFC; decision-making processes and judgement). The research finds that psilocybin increases dendritic spine density in both pyramidal tract (PT) and intratelencephalic (IT) neurons, but only PT neurons are essential for psilocybin's anti-stress effects through 5-HT2A receptor activation.

Bertrand, C., Deisseroth, K., Gray, N. J., Hack, L. M., Heifets, B. D., Hilton, R., Knutson, B., Laudie, J., Rodriguez, C. I., Roessell, P. J. V., Suppes, T., Williams, L. M., Zhang, X.

This randomised, double-blind, placebo-controlled clinical trial (n=16) examines MDMA's (80-120mg) effects on neural circuits in individuals with subthreshold PTSD symptoms and early life trauma. The study finds that participants with higher baseline amygdala reactivity (emotional experiences) showed significant reductions in amygdala and sgACC (emotional processing) activity, increased sgACC-amygdala connectivity, and increased likability of threat expressions after 120mg MDMA compared to those with lower baseline reactivity.

Barnett, L., Carhart-Harris, R. L., Coleman, J. A., Dipasquale, O., Kaelen, M., Muthukumaraswamy, S., Nutt, D. J., Roseman, L., Shinozuka, K., Tromm, R.

This trial re-analysis (n=15) found that LSD (75µg) produces significant changes in dorsolateral prefrontal cortex (DLPFC) functional connectivity that correlate with subjective experiences: ego dissolution was associated with increased connectivity between DLPFC, thalamus and visual processing areas, while emotional arousal correlated with connectivity between right DLPFC, intraparietal sulcus and salience network. MEG analysis revealed increased theta-band information flow between thalamus and DLPFC, supporting the theory that disrupted thalamic gating underlies ego dissolution.

Carter, A., Gardner, J., Ham, R., Liknaitzky, P.

This pre-print qualitative study (n=18) explores therapeutic touch in psychedelic-assisted therapy (PAT) for Generalised Anxiety Disorder (GAD). It finds that most participants valued touch during psilocybin dosing sessions, feeling it provided connection and helped manage intense emotional experiences, with some attributing therapeutic effects to it. The study emphasises the importance of a strong therapeutic relationship and recommends individualised use of touch, alongside further research on safety and therapist training.

Blainey, M. G., Brudner, R. M., Chisamore, N., Doyle, Z., Johnson, D., Kaczmarek, E., McIntyre, R. S., Meshkat, S., Riva-Cambrin, J., Rosenblat, J. D., Weiglein, G.

This secondary analysis of an open-label waitlist-controlled clinical trial (n=27) finds no significant differences in depression, anxiety, and suicidality symptom improvements between treatment-resistant depression (TRD) patients who discontinued antidepressants before psilocybin-assisted psychotherapy (1-3x25mg; PAP/PAT) and those unmedicated at screening.

Kugel, J., Laukkonen, R., Liknaitzky, P., Yaden, D. B., Yücel, M.

This systematic review (s=98) examining psychedelic-catalysed insight found that 86% of studies showed insight was linked to therapeutic improvement, with insight being dose-dependent and significantly higher than placebo in 93% of comparative studies, suggesting insight may be a key mechanism in psychedelic therapy.

DiBerto, J. F., Fay, J. F., Gumpper, R. H., Jain, M. K., Jin, J., Kaniskan, H. Ü., Kapolka, N., Kim, K., Krumm, B. E., Nichols, D. E., Roth, B. L., Sun, N., Sun, R., Xu, Z.

This study presents seven cryo-electron microscopy (cryo-EM) structures showing how different classes of psychedelic and non-psychedelic compounds interact with the serotonin (5-HT) 2A receptor-the primary target for classical psychedelics' therapeutic effects-revealing both shared and distinct binding patterns that could guide the development of new therapeutic compounds with improved side effect profiles.

Becker, A. M., de Jesus, N. M. S., Haijen, E. C. H. M., Hurks, P. P. M., Klaiber, A., Kuypers, K. P. C., Liechti, M. E., Luethi, D., Mueller, L., Müller, F., Schmid, Y., Straumann, I.

This double-blind placebo-controlled trial (n=53) testing LSD microdosing (20μg; 2xp/w; 6w) for adults with moderate to severe ADHD found that while the treatment was safe and well-tolerated, it showed no advantage over placebo in reducing ADHD symptoms, with both groups showing similar improvements on standardised symptom measures.

Aday, J. S., Baker, A. K., Boehnke, K. F., Burgess, H. J., Clauw, D. J., Conroy, D. A., Davis, A. K., Glynos, N., Guss, J., Harte, S. E., Horowitz, D., Hosanagar, A., Mashour, G. A., McAfee, J., Pouyan, N., Scott, K., Tarnal, V., Weston, C.

This open-label, proof-of-concept trial (n=5) of psilocybin-assisted therapy for fibromyalgia finds the treatment to be well-tolerated, with only transient blood pressure elevations and headaches reported. Secondary outcomes show clinically meaningful improvements in pain severity, pain interference, and sleep disturbance one month after treatment, with all participants reporting some degree of symptom improvement.

Bitar, R., Engeli, E. J. E., Gubser, L. P., Halm, S., Herdener, M., Kreis, Y., Moujaes, F. F., Nordt, C., Ort, A., Preller, K. H., Rieser, N. M., Rossgoderer, C., Seifritz, E., Thévenaz, M., Visentini, M., Vollenweider, F. X., von Rotz, R.

This double-blind randomised clinical trial (n=37) found that a single dose of psilocybin (25mg) with brief psychotherapy did not significantly reduce alcohol relapse rates or consumption compared to placebo in patients with alcohol use disorder (AUD) at 4-week or 6-month follow-up, though psilocybin participants reported additional reductions in craving and temptation to drink, suggesting larger trials are needed to evaluate this approach for severely affected patients.

Barrett, F. S., Barta, T., Bazin, O., Biabani, M., Carhart-Harris, R. L., Chambers, R., Chopra, S., Deco, G., Egan, G. F., Greaves, M. D., Khajehnejad, M., Novelli, L., Preller, K. H., Razi, A., Sethi, A., Simonsson, O., Stoliker, D., Sundram, S., Williams, M.

This neuroimaging study (n=62) investigates how psilocybin (19mg) reorganises brain connectivity in different contexts using fMRI and EEG. Participants were scanned before and after ingestion during rest and naturalistic stimuli (meditation, music, and visual). Under psilocybin, brain activity in eyes-closed states became more similar to eyes-open states, with increased connectivity in associative regions and decreased connectivity in sensory areas. The findings suggest that psilocybin induces a state of embeddedness, reducing distinctions between self and environment, which may underlie both its subjective and therapeutic effects.

Carhart-Harris, R. L., Deco, G., Kringelbach, M. L., Nutt, D. J., Pallavicini, C., Perl, Y. S., Piccinini, J. I., Tagliazucchi, E., Timmermann, C.

This computational fMRI study (n=15) examines brain dynamics after DMT (iv; 20mg) administration, focusing on the onset of the psychedelic state. It reveals a peak destabilization of brain dynamics around 5 minutes post-administration and identifies a heightened reactivity phase, primarily affecting fronto-parietal and visual regions. The study links these changes to serotonin 5HT2a receptor density, suggesting these dynamics underpin the psychedelic state's complexity and flexibility.

Balabanov, P., Butlen-Ducuing, F., Guizzaro, L., Silva, F.

This systematic review (s=8) analyses completed controlled trials of psychedelics for depression, including psilocybin, LSD, ayahuasca, and DMT, all in Phase II or I/II. It evaluates methodological patterns against the draft European Medicines Agency guideline revision, highlighting challenges such as unblinding, expectancy, and adverse event characterisation, while calling for larger studies to assess long-term efficacy and safety.

Atli, M., Dunlop, B. W., Feifel, D., Goodwin, G. M., Hellerstein, D. J., Malievskaia, E., Marwood, L., Mistry, S., Nowakowska, A., Shabir, Z., Stansfield, S., Teoh, E., Tsai, J., Young, M. B.

This one-year observational follow-up study (n=66) examined the long-term outcomes of psilocybin (25 mg, 10 mg, 1 mg; COMP360) in treatment-resistant depression (TRD). Median time to depressive relapse was longest in the 25 mg group (92 days) compared to 10 mg (83 days) and 1 mg (62 days), with most participants relapsing by week 12. A post hoc analysis of those entering the follow-up study (n=58) found a more pronounced difference, with the 25 mg group maintaining benefits for 189 days. Adverse events were minimal, with one case of mild suicidal ideation in the 1 mg group.

Fink-Jensen, A., Fisher, P. M., Jensen, M. E., Johansen, S. S., Knudsen, G. M., Messell, C. D., Nielsen, M. K. K., Poulsen, E. D., Stenbæk, D. S., Varga, T. V., Volkow, N. D.

This open-label study (n=10) investigates the effects of single-dose psilocybin (25mg) therapy in adults with severe alcohol use disorder (AUD). It finds significant reductions in alcohol consumption, craving, and increases in self-efficacy over 12 weeks following treatment despite notable between-participant pharmacokinetic variations.

Avedisian, I., Becker, A. M., Erne, L., Grünblatt, E., Humbert-Droz, M., Jelusic, A., Liechti, M. E., Luethi, D., Meyer zu Schwabedissen, H. E., Mueller, L., Straumann, I., Thomann, J., Tolev, A.

This randomised, double-blind, cross-over study (n=23) investigates LSD (100μg) effects after daily paroxetine (SSRI) or placebo administration in healthy participants. It finds paroxetine reduced negative LSD effects (bad drug effect, anxiety, nausea) while maintaining pleasant effects, and caused higher LSD concentrations (1.4-1.5x) due to CYP2D6 inhibition, suggesting no LSD dose adjustment is needed when combined with CYP2D6-inhibiting SSRIs.

Bloch, M. H., Canuso, C. M., Chen, L. N., DelBello, M., Drevets, W. C., Fu, D. J., Kosik-Gonzalez, C., Lane, R., Moreno, C.

This double-blind Phase IIb trial (n=147) evaluated the efficacy, safety, and tolerability of esketamine nasal spray versus midazolam in reducing depressive (MDD) symptoms in adolescents at imminent risk for suicide (SI). The study finds that pooled doses of esketamine (56 and 84 mg) significantly reduce depressive symptoms at 24 hours, with common side effects including dizziness, nausea, and dissociation.

Armand, S., Fisher, P. M., Johansen, A., Knudsen, G. M., Larsen, K., Lindberg, U., Madsen, M. K., McCulloch, D. E-W., Ozenne, B., Stenbæk, D. S.

This single-blind, cross-over study (n=28) using MRI in healthy participants found that psilocybin (18.2mg/70kg) significantly decreased cerebral blood flow (CBF) and internal carotid artery (ICA) diameter. In contrast, ketanserin (20mg) had no significant effect. This finding suggests an asymmetric 5-HT2AR modulatory effect on CBF and provides the first in vivo human evidence of psilocybin-induced ICA constriction.

Lukasiewicz, K., Modzelewski, S., Stankiewisz, A., Waszkiewicz, N.

This systematic review (s=31) examines the side effects of microdosing LSD and psilocybin, finding that adverse effects are typically dose-dependent, mild, and short-lived. Common side effects include increased blood pressure, anxiety, and cognitive impairment. The review highlights the lack of standardised reporting on side effects and calls for future studies to provide more systematic and transparent assessments.

Bogenschutz, M. P., Chenhall, R., Halman, A., Pagni, B. A., Perkins, D., Sarris, J.

This naturalistic longitudinal study (n=66) investigates the long-term effects of ayahuasca on mental health in adults with no prior exposure. Participants attending neo-shamanic ceremonies reported sustained improvements in depression, anxiety, stress, affect, personality traits, spirituality, and relationships up to 12 months. Individuals with depression or anxiety experienced lasting symptom reductions, while those without a diagnosis had short-term benefits. Alcohol and cannabis use decreased only at one month. Findings suggest ayahuasca's mental health benefits persist, with varying trajectories of change over time.

Johnson, M. W., Juliani, A., Klimaj, V., Reggente, N., Safron, A.

This theory-building paper proposes the ALBUS (Altered Beliefs Under Psychedelics) model as an extension of the REBUS hypothesis, suggesting that 5-HT2A receptor activation can lead to both relaxation (REBUS) and strengthening (SEBUS) of beliefs depending on dosage and context. The authors draw parallels between psychedelic states and lucid dreaming, focusing on mechanisms of conscious perception, dreaming, and memory.

Aixalá, M., Anderson, B. T., Breeksema, J. J., Bremler, R., Brennan, W., Burback, L., Calder, A. E., Carhart-Harris, R. L., Cheung, K., Devenot, N., Evans, J., Gorman, I., Greń, J., Hendricks, P. S., Holoyda, B., Jacobs, E., Krecké, J., Kruger, D. J., Luke, D., Majic, T., Mathai, D. S., McGuire, A. L., Mehtani, N. J., Nash, K., Noorani, T. N., Palitsky, R., Robinson, O., Simonsson, O., Stahre, E., van Elk, M., Yaden, D. B.

This survey (n=30) of psychedelic researchers identifies key research gaps in psychedelic harm and safety. It highlights the need to define types of harm, their predictors, and effective treatments. It also calls for better post-psychedelic support, including online resources, peer support, therapy, and psychiatric care. The authors advocate for increased funding, suggesting that psychedelic investors and companies allocate 1% of their investments to safety measures.

Äbelö, A., Aicher, H. D., Dornbierer, D. A., Dornbierer, J., Egger, K., Kost, J., Meling, D., Müller, J., Müller, P., Puchkov, M., Quednow, B. B., Redondo, J. J., Scheidegger, M., Seifritz, E., Smallridge, J. W., van Rotz, R.

This single-blind, randomised, two-arm, factorial, dose-finding study (n=16) investigates the pharmacokinetic and pharmacodynamic interactions between DMT and harmine in an ayahuasca-inspired ('pharmahuasca') formulation. Participants received six dose combinations (0-120 mg DMT, 0-180 mg harmine) via a transmucosal delivery system. Results show dose-dependent subjective effects lasting 4-5 hours, with peak plasma levels (Cmax) of 33 ng/mL for DMT and 49 ng/mL for harmine. Harmine increased DMT bioavailability and plasma half-life while altering its metabolism. The formulation demonstrated a favourable safety profile, supporting its potential for further clinical testing in affective disorders.

Aqil, M., de Hollander, G., Dumoulin, S. O., Knapen, T., Vreugdenhil, N.

This pre-print, multimodal study (n=18) investigates psilocybin’s (5mg and 10mg) effects on perception and brain dynamics using psychophysics, ultra-high field fMRI, and computational modelling. It finds that psilocybin alters contextual perception in the Ebbinghaus illusion, modifies cortical responses to visual stimuli, and proposes a computational model linking these changes, suggesting altered contextual computations as a potential general mechanism of psychedelic action.

Ashraf, I., Azizi, L., Carhart-Harris, R. L., Erritzoe, D., Ertl, N., Nutt, D. J., Roseman, L., Wall, M. B.

This pre-print neuroimaging study (n=38) investigates the effects of MDMA and LSD on striatal connectivity (brain area, movement, and reward systems) using resting-state fMRI. The study finds that while neither drug significantly altered within-network connectivity of the striatum, both substances caused significant changes in connectivity with other brain regions, such as MDMA reducing connectivity between the limbic striatum and the amygdala and LSD increasing connectivity between the associative striatum and the frontal, sensorimotor, and visual cortices.

Brouwer, A., Brown, J., Carhart-Harris, R. L., Erowid, E., Erowid, F., Raison, C. L.

This qualitative analysis of Erowid.org experience reports (n=279) examines the temporal structure (organisation of time) of psilocybin experiences, focusing on the 'come-up' and 'come-down' phases. The study finds that the onset phase typically resembles an acute stress reaction with negative feelings. In contrast, the descending phase is characterised by positive feelings similar to post-stress recovery, suggesting a potentially important therapeutic mechanism.

Garcia-Romeu, A., Jackson, H., Johnson, M. W., Lehrner, A., Lowe, M. X., Mathai, D. S., Nayak, S., Roberts, D. E., Sepeda, N. D.

This prospective, longitudinal study (n=679) examined the effects of psilocybin use on emotional experiences, particularly feelings of shame and guilt. The study found that while most participants had positive experiences with psilocybin, acute feelings of shame or guilt were common (68%), and the ability to work through these feelings positively correlated with well-being in the weeks following use. On average, psilocybin resulted in a small but significant decrease in trait shame, which was maintained for 2-3 months after use, though in a minority of participants (30%), trait shame increased.

Carhart-Harris, R. L., Erritzoe, D., Kettner, H., Lyons, T., Mediano, P. A. M., Rosas, F. E., Spriggs, M. J., Zeifman, R. J.

This single-blind (n=11) study with healthy participants shows that confidence in negative self-beliefs decreased after a high dose of psilocybin (25mg) which predicted increases in well-being four weeks later. This provides the first psychological (vs neurological) information on the validity of the REBUS model.

Fountoulakis, K. N., Saitis, A., Schatzberg, A. F.

This systematic review and meta-analysis (s=87; 2025) finds esketamine's efficacy as an adjunctive therapy for treatment-resistant depression (TRD) to be modest (effect size 0.15-0.23) and comparable to atypical antipsychotics, with no significant effect on suicidality. The review raises concerns about esketamine's abuse potential and unknown long-term effects. It also highlights regulatory issues, including deaths and emerging suicidality during clinical trials.

Bowrey, H. E., Buyze, J., Clemens, K., Godinov, Y., Joshi, K., Pilon, D., Shah, A., Teeple, A., Zhdanava, M.

This secondary analysis (n=321) of the ESCAPE-TRD trial compared work productivity loss (WPL) and related costs in patients with treatment-resistant depression (TRD) receiving esketamine nasal spray (56mg or 84mg) versus quetiapine (atypical antipsychotic) extended release, both combined with an oral antidepressant. By week 8, WPL decreased by 30.3% with esketamine and 17.3% with quetiapine, leading to a cost savings difference of $156 per week. By week 32, WPL reductions were 45.3% (esketamine) and 32.5% (quetiapine), with a weekly cost savings difference of $153.

Bitter, I., Buyze, J., Cebulla, K., Frey, R., Fu, D. J., Godinov, Y., Ito, T., Kambarov, Y., Llorca, P-M., Messer, T., Mulhern-Haughey, S., Oliveira-Maia, A. J., Reif, A., Rive, B., von Holt, C., Young, A. H.

This secondary analysis of an open-label, single-blind, Phase IIIb trial (n=676) compares esketamine nasal spray plus an SSRI/SNRI versus extended-release quetiapine plus an SSRI/SNRI for treatment-resistant depression (TRD). It finds esketamine to be superior in achieving remission at week 8 (27.1% vs. 17.6%, p=0.003) and preventing relapse through week 32 (21.7% vs. 14.1%). Adverse events align with known safety profiles.

Aicher, H. D., Caflisch, L., Dornbierer, D. A., Elsner, C., Hempe, A., Kost, J., Landolt, H-P., Marten, L., Meling, D., Mueller, J., Mueller, M. J., Poetzsch, S. N., Puchkov, M., Quednow, B. B., Scheidegger, M., Seifritz, E., Steinhart, C., Suay, D., Wicki, I.

This secondary analysis of an RCT (n=31) evaluates a novel pharmaceutical formulation of DMT and harmine in healthy male volunteers. The study finds that intranasal DMT and buccal harmine (pharmahuasca) produce consistent pharmacokinetic profiles and safe, well-tolerated effects resembling ayahuasca, with subjective experiences lasting 2-3 hours. This formulation is proposed as a safer, standardised alternative for potential therapeutic use in mental health disorders.

Deijen, J. B., Engelbregt, H., Irrmischer, M., Puxty, D. J., Yildirim, B. O.

This observational study (n=83) examines factors influencing the effects of individual psilocybin-assisted therapy (PAT) on depression, anxiety, PTSD, and personality traits. Results show that a single high dose of psilocybin reduces symptoms of anxiety, depression, and PTSD over three months while increasing openness and conscientiousness. Mystical experiences, emotional breakthroughs, and personal growth, along with demographic factors, moderate these positive changes.

Alonzo, A., Barton, D., Baune, B. T., Berk, M., Carter, G. T., Chatterton, M. L., Dong, V., Fitzgerald, P. B., Glozier, N., Glue, P., Hackett, M., Hadzi-Pavlovic, D., Hood, S., Loo, C., Martin, D., Mihalopoulos, C., Mills, N. T., Mitchell, P. B., Nikolin, S., Rodgers, A., Sarma, S., Somogyi, A. A.

This secondary analysis of a Phase III trial (n=174) evaluates the effects of subcutaneous ketamine on anxiety in treatment-resistant depression (TRD). Significant reductions in anxiety (HAM-A scores) were observed in cohort 2 with flexible dosing (35-63mg/70kg) but not in cohort 1 with fixed low dosing (35mg/70kg). These effects, mediated by changes in depression (MADRS), were not sustained 4 weeks post-treatment.

Boonmak, P., Harding, L., Joshi, K., Pilon, D., Shah, A., Teeple, A., Zhdanava, M.

This retrospective cohort study (n=14,912) examines healthcare resource use (HRU) and costs among patients with major depressive disorder (MDD) and acute suicidal ideation or behaviour (SI) initiated on esketamine nasal spray, ECT, SGA augmentation, or antidepressant monotherapy in the U.S. Esketamine-treated patients (n=122) had lower acute care HRU (0.59 days) and costs ($1869/month) compared to ECT (3.17 days, $4624) and SGA augmentation (0.92 days, $2163), but higher than monotherapy (0.32 days, $863). Esketamine reduced HRU (58%) and costs (50%) most significantly from baseline.

Bhatt, S. R., Bogenschutz, M. P., Carrithers, B. M., Goldway, N., Mennenga, S. E., O'Donnell, K., Pagni, B. A., Ross, S., Zeifman, R. J.

This secondary of a Phase II study (n=84) investigates the effects of psilocybin-assisted therapy (PAT) on personality traits in alcohol use disorder (AUD). Psilocybin (2x, 25-40mg/70kg; n=44) significantly reduced neuroticism and increased extraversion and openness compared to placebo (diphenhydramine, n=40). Decreased impulsiveness correlated with lower alcohol consumption post-treatment, suggesting PAT may normalize abnormal personality traits in AUD.

Atli, M., Gaillard, R., Goodwin, G. M., Kirlic, N., Koelpin, D., Lennard-Jones, M., Malievskaia, E., Modlin, N. L., Peck, S. K.

This article describes the Compass Psychological Support Model (CPSM) used to support participants with treatment-resistant depression undergoing investigational psilocybin treatment. The CPSM aims to ensure a safe and meaningful psychedelic experience, complemented by therapist training, mentoring, and fidelity assessment to maintain delivery quality and consistency.

Aaronson, S. T., LaPratt, J., Lauterbach, M., Miller, T., Sackeim, H. A., Shoultz, A., Suppes, T., Swartz, K., van der Vaart, A.

This open-label trial (n=12) conducted at Sheppard Pratt Hospital finds that psilocybin (25mg) significantly decreases depressive symptoms in patients with severe treatment-resistant depression (TRD) at 3 weeks (MADRS −15.8) and 12 weeks (MADRS −17.2) post-treatment. Exploratory analyses suggest the Oceanic Boundlessness dimension correlates with antidepressant responses, while patients with comorbid PTSD show reduced antidepressant effects.

Carhart-Harris, R. L., Daily, Z. G., Milliere, R., Sanders, J. W., Timmermann, C.

This phenomenological study (n=23) investigates DMT-induced immersive experiences and encounters with autonomous presences during fMRI scanning. Using micro-phenomenological interviews, it identifies structural features and temporal dynamics of DMT experiences, highlighting layered sensory, spatial, self-related, and social effects that extend beyond ego dissolution or mystical experiences.

Kuypers, K. P. C., Mason, N. L., Ramaekers, J. G., Reckweg, J., Theunissen, E. L., Toennes, S. W.

This cross-over, placebo-controlled trial (n=14) assesses the effects of escalating doses of 3-MMC (25, 50, 100mg) on vital signs, neurocognitive function, state of consciousness, appetite, and drug desire. Results show dose-dependent increases in heart rate and blood pressure (not clinically significant), enhanced neurocognitive task performance, and mild dissociative and psychedelic effects. Participants reported decreased appetite and transient increases in liking and wanting 3-MMC. Low to moderate doses were well tolerated and safe, with potential risks associated with high doses.

Bekinschtein, T., Bruno, N., Cavanna, F., Copa, D., D'Amelio, T., de la Fuente, L. A., Lewis-Healey, E., Muller, S., Pallavicini, C., Tagliazucchi, E.

This repeated-measures dose-dependent study (n=19) investigates DMT's subjective and neural dynamics under naturalistic conditions. Participants received 20mg or 40mg doses of freebase DMT in a blinded, counterbalanced design, with EEG data and time-resolved subjective measures collected. The 40mg dose produced more intense visual hallucinations and emotional responses. Neural analyses revealed alpha power and permutation entropy were most associated with subjective experiences, whereas lempel-ziv complexity was less predictive, challenging prior assumptions about its role in psychedelic states.

Fitzgerald, P. B., Hunt, P., Nutt, D. J., Schlag, A. K.

This review (2024) examines the recent approval by the Australian Therapeutic Goods Administration (TGA) of psilocybin for treatment-resistant depression (TRD) and MDMA for PTSD, effective 1 July 2023. It highlights the campaign led by Mind Medicine Australia and supported by leading researchers and institutions, as well as implications for future approvals and psychedelic drug development pathways.

Becker, A. M., Eckert, A., Erne, L., Klaiber, A., Liechti, M. E., Luethi, D., Müller, L., Nuraj, A., Rudin, D., Varghese, N., Vogt, S. B., Zuparic, M.

This double-blind, randomised, placebo-controlled, crossover study (n=22) investigates the dose-dependent effects and pharmacokinetics of continuous intravenous DMT infusions over 120 minutes. It finds dose-proportional pharmacokinetics, a rapid onset of subjective effects that plateaus at 30 minutes, and a ceiling effect for positive effects at 1.8 mg/min. Higher doses (2.4 mg/min) induce anxiety and ego dissolution. Moderate acute tolerance and successful self-titration for desired effects were observed.

Dziobek, I., Jungwirth, J., Preller, K. H., Vollenweider, F. X., von Rotz, R.

This re-analysis of an RCT (n=51) investigates the effects of psilocybin-assisted therapy on empathy in depressed patients. Participants received either a single psilocybin dose (15mg/70kg) or placebo within a 4-week psychological support programme. Psilocybin significantly improved emotional empathy, particularly towards positive stimuli, for up to two weeks compared to placebo.

Aaronson, S. T., Alvarez, O., Carhart-Harris, R. L., Chai-Rees, J., Croal, M., Debattista, C., Dunlop, B. W., Feifel, D., Goodwin, G. M., Hellerstein, D. J., Husain, M. I., Kelly, J. R., Kirlic, N., Licht, R. W., Malievskaia, E., Marwood, L., Meyer, T., Mistry, S., Nowakowska, A., Páleníček, T., Repantis, D., Schoevers, R. A., Simmons, H., Somers, M., Teoh, E., Tsai, J., Wahba, M., Williams, S., Young, A. H., Young, M. B., Zisook, S.

This re-analysis of the COMPASS Phase IIb trial (n=233) investigates the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcomes in treatment-resistant depression. Participants received a single dose of 25, 10, or 1 mg of psilocybin (COMP360) with psychological support. Higher doses produced stronger psychedelic effects, and reductions in depression (MADRS scores) at Week 3 correlated most strongly with dimensions of Oceanic Boundlessness (r = −0.508), Visual Restructuralization (r = −0.516), and Emotional Breakthrough Inventory (r = −0.637). Findings suggest the quality and intensity of psychedelic experiences mediate therapeutic outcomes and support dose-response mechanisms.

Bessa, B. S., Breeksema, J. J., d'Orsi, D., Dinis-Oliveira, R. J., Schimmers, N., Schoevers, R. A., Seybert, C., Silva, L., Veraart, J. K. E.

This systematic review (s=45) on psychedelic-assisted psychotherapy for mental disorders finds that psychological interventions are reported with low completeness and high heterogeneity. It also finds that MDMA studies are more homogeneous, with greater procedural detail.

Back, A., Baker, K. K., Freeman-Young, T. K., Gooley, T. A., Harvey, K., Kaelen, M., Kelmendi, B., Kollefrath, A., McGregor, B., Morgan, L., Myers, S., Sethi, T., Sorta, D., Tai, M., Thomas, B. J.

This double-blind randomised trial (n=30) finds that psilocybin therapy significantly reduces symptoms of depression in clinicians after frontline work during the COVID-19 pandemic. Psilocybin (25mg) showed greater reductions in depression (MADRS scores) and PTSD symptoms compared to the niacin control, though PTSD findings were not statistically significant.

Carhart-Harris, R. L., Erritzoe, D., Godfrey, K., Lyons, T., Peill, J. M., Spriggs, M. J., Weiss, B., Zhang, X.

This re-analysis of a single-blind, fixed-order trial (n=28) investigates the effects of a single high-dose psilocybin (25 mg) on personality traits in psychedelic-naïve healthy volunteers. It finds significant reductions in neuroticism one month post-administration, moderated by subjective experience meaningfulness and ego dissolution, suggesting psilocybin catalyses lasting personality changes with therapeutic potential.

Barta, S., Brooker, J., O’Callaghan, C.

This systematic review (2024; s=9) of healthcare workers' attitudes and knowledge about psychedelic-assisted therapy for patients with serious illness finds polarized views, with most acknowledging potential benefits but desiring further education and a stronger evidence base.

Barnett, B. S., Coulson, A. J., Delatte, M. S., Greer, G. R., Hendricks, P. S., King IV, F., Mauney, E. E., Murnane, K. S., Nayak, S., Vest, M. F.

This perspective article (2024) for investigators at academic medical centres in the United States provides recommendations for establishing psychedelic research programs. It highlights challenges including funding, regulatory approvals, sourcing controlled substances, preparing study spaces, managing controlled substances, and engaging the local community, and offers strategies to anticipate and surmount these obstacles.

Carhart-Harris, R. L., Jerotic, K., Kringelbach, M. L., Mediano, P. A. M., Preller, K. H., Shinozuka, K., Zhao, A. T.

This systematic review (2024) and meta-analysis (s=44) finds that medium/high doses of LSD yield higher ratings of visionary restructuralisation than psilocybin. It also reports that psychedelics strengthen between-network functional connectivity and diminish within-network connectivity, and that LSD induces more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, while receptor selectivity differences remain negligible.

Blomqvist, O., Cardoner, N., Diels, J., Fagiolini, A., Falkai, P., Godinov, Y., Llorca, P-M., Mulhern-Haughey, S., Nielsen, R. E., Reif, A., Rive, B., Young, A. H.

This robustness analysis of the ESCAPE-TRD Phase IIIb trial (n=676) investigates esketamine nasal spray versus quetiapine extended release for treatment-resistant depression (TRD). Esketamine significantly outperformed quetiapine in achieving remission at week 8 (MADRS ≤10) and maintaining relapse-free status through week 32, with hazard ratios favouring esketamine (HR: 1.658-1.711, p < 0.001).

Agnorelli, C., Bohl, B., Carhart-Harris, R. L., Douglass, H., Erritzoe, D., Fagiolini, A., Godfrey, K., Nutt, D. J., Parastoo, H., Sawicka, G., Spriggs, M. J.

This review (2024) examines the effects of classic psychedelics (e.g., LSD, psilocybin, DMT) and non-classic psychedelics (e.g., ketamine, MDMA) on neuroplasticity. Drawing on preclinical and clinical studies, it discusses molecular, structural, and functional changes induced by these agents, highlighting their potential to re-open developmental windows (hyper-plasticity) and increase nervous system sensitivity to stimuli (meta-plasticity). Translating findings to humans remains challenging, but emerging tools like PET radioligands and multimodal approaches offer promise for future research.

Calder, A. E., Hase, A., Hasler, G.

This meta-analysis (s=29) examines the effects of psychedelics (including ketamine and MDMA) and two other 'psychoplastogens' on peripheral BDNF levels in humans. It finds no significant changes in BDNF levels post-administration (SMD=0.024, p=0.64), regardless of drug, dose, participant age, or psychiatric condition. Studies with better-controlled designs report smaller effect sizes, and later timepoints show minimal increases in BDNF. The authors conclude that peripheral BDNF is likely not a reliable marker of rapid neuroplasticity and recommend neuroimaging or stimulation-based methods for future research.

Doss, M. K., Kloft, L., Mallaroni, P., Mason, N. L., Otgaar, H., Ramaekers, J. G., Reckweg, J., Tupper, N., van Oorsouw, K.

This observational study (n=24) examines the acute effects of ayahuasca on memory in experienced Santo Daime members (>500 lifetime uses). Findings show ayahuasca enhances memory accuracy and recollection while not impacting familiarity or false memory, suggesting β-carboline activity may drive selective improvements in hippocampal-dependent processes.

Beaglehole, B., Day-Brown, R., de Bie, A., Glue, P., Hughes-Medlicott, N. J., Kimber, B., McNaughton, N., Muirhead, C., Neehoff, S., Shadli, S. M.

This randomised, double-blind, psychoactive-controlled study (n=12) compared intramuscular ketamine (35-70mg/70kg) to fentanyl (50μg) in treatment-resistant OCD patients, with 10 participants completing the trial. The study found dose-dependent reductions in OCD symptoms (Y-BOCS scores) for ketamine compared to fentanyl, with effects lasting up to 168 hours, though two participants dropped out due to dissociative effects.

Böge, K., Correll, C. U., Curtis, L., De Pieri, M., Glangetas, A., Kaiser, S., Kirschner, M., Leucht, S., Mallet, L., Penzenstadler, L., Preller, K. H., Richard-Lepouriel, H., Sabé, M., Seragnoli, F., Solmi, M., Sulstarova, A., Thorens, G., Zullino, D.

This systematic review (2024) and meta-analysis (s=131) examines the incidence of psychedelic-induced psychosis, focusing on individuals with schizophrenia. It finds an incidence of 0.002% in population studies, 0.2% in UCTs, and 0.6% in RCTs, with 3.8% of UCT participants with schizophrenia developing long-lasting psychotic symptoms. It also reports that 13.1% of those with psychedelic-induced psychosis later developed schizophrenia.

Miner, N. B.

This pharmacokinetic study (n=16 + n=51 data from earlier study) investigates the effects of food on MDMA pharmacokinetics and uses population and physiologically based pharmacokinetic models to simulate clinical dosing regimens. Results show that a high-fat/high-calorie meal delays Tmax but does not alter plasma concentrations, with no clinically meaningful covariates identified. Simulations reveal MDMA is a potent CYP2D6 inhibitor but has negligible impact on drugs sensitive to renal transport, informing drug-drug interaction potential and dosing strategies.

Aday, J. S., Baker, A., Barron, J., Boehnke, K. F., Glynos, N., Herberholz, M., Kruger, D. J., Pouyan, N., Woolley, J. D.

This survey (n=581) evaluates the Psychedelic-related Major Life Changes Questionnaire (P-MLCQ) in people reporting naturalistic psychedelic use. It finds that 82.96% of participants reported major life changes in at least one domain, including goals (53.7%), values (53.53%), and spirituality (49.05%), with changes rated highly positively (M = 4.64/5). Frequency of use correlated with more changes (r = 0.34), while education level was negatively associated with the number of changes (β = -0.137).

Humbert-Droz, M.

This pooled analysis of two RCTs (n=48) investigates the safety of mescaline in single oral doses of 100-800 mg (96 administrations). Positive subjective effects increased dose-dependently, while autonomic effects were moderate. Adverse effects, including nausea (dose-limiting), were recorded, but no significant issues with liver/kidney function or blood cell counts occurred. Flashbacks were reported in 2% of administrations. Mescaline doses up to 800 mg were deemed safe in a controlled clinical setting for healthy participants.

Bola, M., Brzezicka, A., Hobot, J., Kołodziej, A., Magnuski, M., Orłowski, P., Ruban, A.

This comparative study (dataset I: n=70, II: n=38) explores differences between naturalistic psychedelics users and non-users during the processing of self-related thoughts, using behavioural testing combined with EEG and source localization. Results from Dataset I suggest weaker increases in alpha and beta power in psychedelics users, primarily in brain regions linked to processing self-related information and memory. However, Dataset II did not replicate these effects, possibly due to sample size and spatial resolution limitations.

Kamboj, S. K., McAlpine, R.

This mixed-methods investigation (n=16 psilocybin retreat participants; n=529 online survey respondents) explores strategies for navigating challenging psychedelic experiences and their link to emotional breakthroughs. Three primary strategies-Acceptance and Reappraisal, Sensory Regulation and Physical Interaction, and Social Support and Disclosure-emerged, with the first and third positively associated with emotional breakthroughs. Fear-related challenges were negatively associated with breakthroughs, indicating the need for adaptive coping strategies to optimize therapeutic and safety protocols.

Blainey, M. G., Brudner, R. M., Doyle, Z., Gomes, F. A., Kaczmarek, E., Mansur, R. B., McIntyre, R. S., Meshkat, S., Rosenblat, J. D., Weiglein, G.

This subgroup analysis of a trial on treatment-resistant depression (n=4) evaluates the safety and efficacy of psilocybin (25 mg) in individuals with Bipolar II disorder. Results show a reduction in MADRS scores from 32.5 at baseline to 21.3 at 6 months, with no emergent mania, hypomania, or psychosis, suggesting potential improvement in depressive symptoms.

Dua, A. N., Kwan, A. C., Liao, C., Liston, C., Wojtasiewicz, C.

This review (2024) highlights preclinical research from the past 15 years showing that ketamine and psychedelics trigger dendritic spine growth in cortical pyramidal neurons, enhancing neural plasticity. It compares the longitudinal effects of psychoactive drugs, emphasizing rapid-onset and sustained structural plasticity as key features of rapid-acting antidepressants, and discusses gaps in understanding and prospects for other interventions like rTMS.

Stanghellini, G.

This cost-effectiveness analysis compares MDMA-assisted therapy (MDMA-AT) versus placebo with therapy (PT) for chronic PTSD treatment over 5 years. Using a health state-transition model, it finds MDMA-AT to be cost-effective with an ICER of $83,845 per QALY (below the $150,000 willingness-to-pay threshold), despite higher intervention costs ($48,376 vs $12,376), due to reduced healthcare visits and better health outcomes (0.377 QALY increment).

Beidas, Z., Fewster, E. C., Husain, M. I., Lake, S., Lucas, P., Petranker, R., Sobolenko, V., Syed, O. A.

This online survey (n=6,193; 2,488 microdosers) examines differences between exclusive microdosers and those who use both micro and macrodoses of psychedelics. The study finds exclusive microdosers were typically older, more likely to be female and non-Caucasian, with psilocybin (74.5%) and LSD (34.4%) being the most commonly used substances, primarily for general wellbeing (73.0%).

Cullen, K. R., Evans, M. D., Jungers, S., Nielson, J. L., Schallmo, M.-P., Swanson, L. R., Varghese, R.

This placebo-controlled study (n=6) investigates how psilocybin (25mg) affects visual surround suppression compared to placebo (100mg niacin). The study finds increased surround suppression effects under psilocybin, with stronger suppression correlating with more intense subjective visual effects.

Atila, C., Beck, J., Christ-Crain, M., Holze, F., Liechti, M. E., Straumann, I., Vizeli, P.

This secondary of four RCTs (n=96) finds that MDMA (100mg or 125mg) induced hyponatremia in 31% of participants, with none occurring in the fluid-restricted group (n=15) compared to 37% in the unrestricted group (n=81). The study challenges previous understanding by showing hyponatremia correlates with increased oxytocin (433% increase) rather than vasopressin levels, suggesting oxytocin mimics vasopressin's effects in the kidneys.

Alpert, M., Mithoefer, A. T., Mithoefer, M. C., Nicholas, C. R., O'Donnell, K., Okano, L., Ot’alora G, M., Poulter, B., Thomas, C.

This theoretical framework paper analyses two Phase III trials of MDMA-assisted therapy for PTSD, describing the conceptual underpinnings and therapeutic approach. It explains how the treatment combines three MDMA-facilitated sessions with non-drug psychotherapy sessions, emphasizing the patient's inner healing intelligence as the primary change agent and the therapeutic relationship as the core facilitating condition.

Earleywine, M., Falabella, G. S., Low, F., Oliva, A. B.

This survey study (n=457) explores the relationship between dysfunctional attitudes and well-being in the context of psychedelic-assisted therapy. It finds that post-acute changes in these attitudes significantly influence well-being, with emotional breakthroughs having a greater impact than challenging or mystical experiences.

Huster, D., Maiti, S., Mote, K. R., Saha Roy, D., Singh, A., Vaidya, V. A.

This lab study used different ways of looking at cells to see how the psychedelic drug DOI affects the outer layer of cells (lipid membrane). The study found that DOI is over 100 times stronger than serotonin at disrupting the cell's outer layer, helping small bubble-like structures combine with cells, and making it easier for tiny holes to form in cell membranes. This suggests that psychedelics might affect the brain not just by binding to receptors (their usual known method), but also by physically changing how cell membranes work and help create new connections.

Dunlop, B. W., Hyatt, C. S., Maples-Keller, J. L., Phillips, N. L., Rakofsky, J., Rauch, S. A. M., Reiff, C. M., Rothbaum, B. O., Sharpe, B. M., Sherrill, A., Yasinski, C.

This pre-registered randomised placebo-controlled study (n=34) investigates the effects of MDMA (100mg) administration on personality traits and affective states in healthy adults. While no statistical significance was found for the primary hypotheses, medium effect sizes were observed for increased Openness (d = 0.79) and Positive Affect (d = 0.51) 48 hours after MDMA administration compared to placebo.

Mallaroni, P., Mason, N. L., Ramaekers, J. G., Satterthwaite, T. D., Singleton, S. P.

This pre-print, double-blind, placebo-controlled crossover study (n=22) investigates the neural effects of 2C-B (20mg) compared to psilocybin (15mg) and placebo using 7T resting-state functional MRI. The results reveal that both 2C-B and psilocybin reduce intra-network connectivity while enhancing between-network connectivity, with 2C-B showing less impact on certain connectivity measures but greater transmodal connectivity.

Enriquez-Geppert, S,, Lietz, M. P., O'Higgins, F.

This randomised feasibility study (n=37) evaluates psilocybin-assisted (microdoses x 6) frontal-midline theta neurofeedback (NF) to improve executive functions (EFs) in participants with psychiatric disorders. Despite no significant improvements in tasks-based EFs, the experimental group reported medium to high gains in daily EFs, indicating the potential benefits of this neuromodulation technique for enhancing daily functioning.

Fleury, S., Nautiyal, K. M.

This preprint mouse study (n=29) finds that the serotonin 1B receptor (5-HT1BR) is necessary for psilocybin's antidepressant and anxiolytic effects, independent of its hallucinogenic properties. Using transgenic mice lacking 5-HT1BR and network analysis, the study demonstrates that this receptor influences brain-wide activity patterns and mediates acute and persistent behavioural responses to psilocybin, suggesting a novel mechanism for psilocybin's therapeutic effects.

Olami, A., Peled-Avron, L.

This meta-analysis (s=5, n=158) of classic psychedelic effects on empathy using the Multifaceted Empathy Test (MET) finds significant enhancement of explicit and implicit emotional empathy, with no effect on cognitive empathy. The analysis covers studies up to November 2023 examining LSD, psilocybin, and ayahuasca.

Jylkkä, J., Krabbe, A., Sikka, P.

This internet survey (n=629) examines how psychedelic experiences relate to psychological flexibility and mental well-being in classical psychedelic users. Network analysis shows psychological insight links to acceptance, while mediation analysis reveals psychological flexibility mediates the relationship between psychedelic use and well-being, suggesting experience quality matters more than frequency of use.

Carhart-Harris, R. L., Douglass, H., Erritzoe, D., Espasiano, L., Gazzaley, A., Girn, M., Godfrey, K., Hampshire, A. D. G., Kerkelä, L., Kettner, H., Lyons, T., Mediano, P. A. M., Nutt, D. J., Oestreich, L., Pagni, B. A., Rosas, F. E., Roseman, L., Sharif, F., Spriggs, M. J., Timmermann, C., Trender, W., Wall, M. B., Zeifman, R. J.

This pre-print, placebo-controlled, within-subjects neuroimaging study (n=28) of psychedelic-naive participants finds that a single high dose of psilocybin (25mg) produces anatomical and functional brain changes from one hour to one month post-dosing. These include decreased axial diffusivity in prefrontal-subcortical tracts, reduced brain network modularity (linked to improved well-being), and increased cortical signal entropy that predicts long-term psychological benefits. These effects were not observed with a 1 mg placebo dose.

Croal, M., Goodwin, G. M., Marwood, L., Mistry, S., Simmons, H., Tsai, J., Young, M. B.

This post hoc analysis (n=233) of a Phase II RCT investigates the impact of recent antidepressant discontinuation (n=156) on the efficacy of psilocybin in treating treatment-resistant depression (TRD). The study compares outcomes between participants who discontinued antidepressants during screening and those who entered the trial free of these medications, finding no significant relationship between antidepressant discontinuation and worsening depression severity or compromised psilocybin treatment efficacy.

Agin-Liebes, G. I., Bogenschutz, M. P., Griffiths, R. R., Grinband, J., Kinslow, C. J., Petridis, P. D., Ross, S., Zeifman, R. J.

This pooled analysis of two Phase II RCTs (n=79) evaluates psilocybin-assisted psychotherapy (PAP/PAT) for cancer-related distress. PAT significantly improves anxiety, depression, interpersonal sensitivity, hostility, obsession-compulsion, and somatization without inducing lasting phobia, paranoia, or psychosis.

Blackburne, G., Fabus, M., Kamboj, S. K., Liardi, A., McAlpine, R., Mediano, P. A. M., Skipper, J. I.

This naturalistic EEG study (n=29) examines the effects of inhaled synthetic 5-MeO-DMT (12mg) on brain activity in healthy individuals. It finds that 5-MeO-DMT radically reorganises low-frequency neural activity flows, making them incoherent, heterogeneous, and nonrecurring. It also causes broadband activity to exhibit slower, more stable, low-dimensional behaviour with increased energy barriers to rapid global shifts.

Bostoen, T., Dadiomov, D., Dahan, A., Dahan, J. D. C.

This meta-analysis (2024, s=31) examines the correlation between subjective effects and therapeutic outcomes for ketamine (s=23, n=471) and psilocybin (s=8, n=183) in depression and substance use disorder (SUD) treatment. It finds modest mediating effects of subjective experiences on therapeutic outcomes, with psilocybin showing a stronger mediating effect (R² = 24%) compared to ketamine (R² = 5-10%), and a greater mediating effect observed in SUD compared to depression regardless of the substance used.

Kamboj, S. K., Lee, J., Mandy, W., Orsini, A., Rice, C., Schlosser, M., Stroud, J.

This online survey (n=233) of autistic participants with high autism quotient scores examines their experiences with psychedelic drugs and perceived changes attributed to their most 'impactful' psychedelic experience. It finds that the majority of participants reported reductions in psychological distress (82%) and social anxiety (78%), and increases in social engagement (70%), while 20% reported undesirable effects such as increased anxiety.

Becker, A. M., Erne, L., Jelusic, A., Klaiber, A., Liechti, M. E., Luethi, D., Schmid, Y., Straumann, I., Thomann, J.

This randomised, double-blind, placebo-controlled, crossover study (n=16) investigates the dose-dependent acute effects, pharmacokinetics, and mechanism of action of mescaline (100-800mg; 5x) in healthy subjects. It finds that mescaline induces dose-dependent subjective effects, increases blood pressure and heart rate, and has dose-proportional pharmacokinetics, with effects primarily mediated by 5-HT2A receptors as demonstrated by ketanserin co-administration.

Aaronson, S. T., Bostian, C., Conlan, E., Eisen, K., Ellis, S. P., Feng, W., Fischer, E., Lean, M., Ostacher, M., Schwartz, G., Suppes, T.

This open-label trial (n=15) evaluates the efficacy and safety of psilocybin (25mg) in veterans with severe treatment-resistant depression (TRD). It finds that 60% of participants met response criteria and 53% met remission criteria at 3 weeks post-treatment, with 47% maintaining response and 40% maintaining remission at 12 weeks.

Aicher, H. D., Caflisch, L., Dornbierer, D. A., Dornbierer, J., Egger, K., Meling, D., Mueller, J., Pfeiffer, D. J., Redondo, J. J., Scheidegger, M., Schlomberg, J. T. T., Smallridge, J. W., Temperli, E., Vasella, E. A.

This double-blind, placebo-controlled study (n=40) investigates the effect of DMT-harmine ('pharmahuasca') on meditative states during a 3-day retreat with experienced meditators. It finds that participants who received DMT-harmine reported greater mystical-type experiences, non-dual awareness, and emotional breakthrough during acute effects, as well as greater psychological insight one day later, compared to the placebo group.

Baker-Jones, M., Barba, T., Carhart-Harris, R. L., Erritzoe, D., Giribaldi, B., Greenway, K. T., Martell, J., Murphy-Beiner, A., Murphy, R., Nutt, D. J., Timmermann, C., Weiss, B.

This 6-month follow-up of a Phase II, double-blind, randomised controlled trial (n=59) finds sustained improvements in depressive symptoms for both psilocybin therapy (PT) and escitalopram treatment (ET) for moderate-to-severe major depressive disorder (MDD). PT shows greater improvements in psychosocial functioning, meaning in life, and psychological connectedness compared to ET at the 6-month follow-up.

Bird, C., Butler, M., Campbell-Coker, K., Cheema, S., Dunbar, F., Hambleton, S., Lambru, G., Maggio, C., Matharu, M., Rucker, J., Seynaeve, M.

This open-label study (n=4) investigated the effects of low-dose oral psilocybin (5-10mg) with psychological support in patients with chronic short-lasting unilateral neuralgiform headache attacks (SUNHA). The study aimed to assess cognitive effects, safety, tolerability, and impact on headache severity and frequency, but was terminated early due to recruitment difficulties.

Calder, A. E., Hasler, G., Holze, F., Liechti, M. E., Rausch, B.

This comparative study (n=56) investigates the relationship between antidepressant effects and acute drug effects of LSD and psilocybin in 28 patients undergoing psychedelic-assisted therapy (PAT) in Switzerland and 28 healthy volunteers from a randomised, double-blind crossover trial. The study finds similar ratings of overall drug effect and mystical experience across groups, but lower ratings of ego dissolution in patients. It identifies relaxation during PAT sessions as the greatest predictor of antidepressant outcomes.

Ables, J. L., Banerjee, R., Cohen, J., DeVita, R. J., Fremont, R. T., Garcia-Ocaña, A., Govindarajulu, U., Israel, L., Kumar, K., Liu, H., Lu, G., Murrough, J. W., Stewart, A., Wang, P., Wood, O.

This open-label single ascending dose Phase I trial (n=25) determines the maximum tolerated dose (MTD) of oral pharmaceutical-grade harmine (component of ayahuasca brew) in healthy adults. It finds that doses <189mg/70kg can be administered with minimal or no adverse events, while doses >189mg/70kg are associated with vomiting, drowsiness, and limited psychoactivity.

Bonnelle, V., Carhart-Harris, R. L., Feilding, A., Nutt, D. J., Rosas, F. E., Timmermann, C.

This re-analysis of a single-blind study (n=17) investigates the role of the autonomic nervous system in DMT-induced peak experiences (20mg, iv). It finds that balanced activity between the fight-or-flight and rest-and-digest systems (sympathovagal coactivation) is linked to stronger feelings of spirituality and insight during DMT sessions and improved well-being two weeks later. The study also notes that a person's nervous system (sympathovagal) balance before taking DMT can predict how insightful their experience will be.

Borkel, L. F., Fernández-Borkel, T., García-Serrano, I., Henríquez-Hernández, L. A., Hernández-Álvarez, E., Quintana-Hernández, D. J., Rojas-Hernández, J., Zumbado, M.

This case study (n=1) finds that a single low dose of 5 µg (0.38µg/kg) of 1cp-LSD on a 13-year-old female dog with a history of separation-related behavioural problems significantly reduced anxiety after two hours. No adverse effects or signs of a psychedelic experience were observed during the 5.5-hour trial.

Marseille, E., Rab, S. F., Raison, C. L.

This health economics study (n=14.8 million) estimates the potential demand for psilocybin-assisted therapy (PSIL-AT) for major depressive disorder (MDD) and treatment-resistant depression (TRD) in the United States. It finds that 24% (lower-bound; 2.2m), 56% (mid-range; 5.1m), and 62% (upper-bound; 5.6m) of patients with MDD or TRD may be eligible for PSIL-AT, with variance largely influenced by exclusion criteria and comorbidity considerations.

Banks, M. I., Dunne, J. D., Hutson, P. R., Krause, B. M., Lennertz, R. L., Nicholas, C. R., Raison, C. L., Riedner, B. A., Roseman, L., Sauder, C. J., Smith, R. F., Wenthur, C. J.

This open-label study (n=8) co-administered psilocybin (25mg) with the amnestic benzodiazepine midazolam to assess the role of memory in the therapeutic effects of psilocybin. It finds that midazolam partially impaired memory while allowing a conscious psychedelic experience, with memory impairment inversely associated with salience, insight, and well-being induced by psilocybin, suggesting a role for memory in its therapeutic effects.

Avram, M., Borgwardt, S., Coenen, R., Fortea, L., Holze, F., Korda, A., Ley, L., Liechti, M. E., Müller, F., Radua, J., Rogg, H., Vizeli, P., Wollner, L.

This double-blind, placebo-controlled, crossover trial (n=28) finds that LSD (100μg), d-amphetamine (40mg), and MDMA (125mg) reduced network integrity in healthy volunteers. LSD uniquely reduced default-mode network integrity and showed more pronounced effects on network segregation and seed-based connectivity compared to amphetamines.

Askins, B. C., Carangan, A. M. J. M., Carreras-Gallo, N., Dawson, K., Dawson, M., Dwaraka, V. B., Higgins-Chen, A. T., Klunder, J., Mallin, M., Megilligan, S., Mendez, T. L., Perkins, N., Sehgal, R., Smith, R.

This preprint open-label study (n=20) examines the effects of ketamine infusions (35mg/70kg, 6x) on biological ageing markers in individuals with depression (MDD) or PTSD. It finds reductions in epigenetic age as measured by OMICmAge, GrimAge V2, and PhenoAge biomarkers, as well as significant changes in Epigenetic Biomarker Proxies (EBPs) and surrogate protein markers following a 2-3 week treatment course. The study also reports expected decreases in depression and PTSD scores as measured by PHQ-9 and PCL-5.

Godfrey, K., Mabidikama, C., Murphy, R. J., Muthukumaraswamy, S., Roberts, R. P., Sumner, R. L., Sundram, F.

This re-analysis of an RCT (n=80) finds no effect of LSD microdosing (10µg, x14) on creativity in healthy adult males. Participants received either LSD or placebo every third day for six weeks, with creativity assessed using multiple tests at baseline, during acute dosing, and after the six-week regimen.

Graziosi, M., Hinkle, J. T., Nayak, S., Yaden, D. B.

This systematic review (2024) and meta-analysis (s=214, n=3504) examines adverse events (AEs) associated with classic psychedelics in clinical or research settings. It finds that serious AEs were rare, occurring in approximately 4% of participants with preexisting neuropsychiatric disorders, while no serious AEs were reported in healthy participants.

Arikci, D., Becker, A. M., Dolder, P. C., Holze, F., Ley, L., Liechti, M. E., Müller, F., Schmid, Y., Straumann, I., Studerus, E., Vizeli, P.

This pooled analysis of nine double-blind, placebo-controlled, cross-over studies (n=213) investigates predictors of LSD effects in healthy subjects. It finds that LSD dose is the most influential predictor, with pre-drug mental states, personality traits, and previous hallucinogen experiences also significantly affecting the subjective experience.

Goldy, S. P., Griffiths, R. R., Weiss, B., Yaden, D. B.

This review (2024) examines the acute subjective effects of classic psychedelics, their relationship to risks and therapeutic benefits, and the current limitations in measuring these effects. It discusses existing measures, their construct validity, and predictive value for outcomes, while proposing recommendations for improving conceptualization and measurement in future research.

Anderson, T. L., Asadipooya, A., Keady, J. V., Neeley, R. E., Ortinski, P. I., Songrady, J., Tavakoli, N. S., Turner, J. R.

This cell-based study investigates the role of serotonin receptors in the claustrum's response to psychedelic drugs. It finds that the claustrum is rich in 5-HT2C receptors on glutamatergic neurons and that serotonin and the psychedelic DOI have opposite effects on synaptic signalling, both mediated by 5-HT2C receptors rather than 5-HT2A receptors as previously thought.

Carhart-Harris, R. L., Curtin, J., Dunne, J. D., Goldberg, S. B., Jiwani, Z., Schlosser, M., Simonsson, O., Stroud, J., Webb, C. A., Young, J.

This cross-sectional survey study (n=863) of meditators with psychedelic experience finds that most participants (73.5%) perceive psychedelic use as beneficial to their meditation practice. The study identifies four key predictors of this perceived benefit: regularity of psychedelic use, intention setting during use, agreeableness, and exposure to DMT.

Avedisian, I., Eckert, A., Klaiber, A., Liechti, M. E., Luethi, D., Rudin, D., Straumann, I., Varghese, N.

This double-blind, randomised, placebo-controlled, crossover study (n=24) compares the acute effects of MDMA, S-MDMA, R-MDMA (the left and right-handed parts of MDMA), and placebo in healthy participants. It finds that S-MDMA (125 mg) induced stronger subjective effects and higher increases in blood pressure than R-MDMA and racemic MDMA while also increasing plasma prolactin, cortisol, and oxytocin more significantly. The study also notes differences in elimination half-lives and metabolite concentrations between the different forms of MDMA.

de Wit, H., Glazer, J., Haggarty, C. J., Lee, R., Molla, H. M., Tare, I.

This double-blind, randomised, placebo-controlled study (n=39) examines the effects of a single low dose of LSD (26µg) on event-related potentials during an emotional face oddball task. It finds that LSD significantly reduced the amplitude of N170 ERP to neutral faces and P300 ERP to neutral and happy faces, suggesting differential effects on brain responses to social and emotional information.

Ferro, M., Lamanna, J., Moro, A. S., Saccenti, D., Salvetti, G.

This systematic review (2024) and meta-analysis (s=12) examines the therapeutic effects of single-dose and two-dose psilocybin administration on depressive symptom severity in MDD and TRD patients. It finds that psilocybin is highly effective in reducing depressive symptoms in both patient groups, with two-dose treatments potentially offering more pronounced and lasting effects (but no statistically significant difference).

Herpers, J., Maximets, N., Van Dongen, N. N. N., Vermetten, E., Zijlmans, J.

This survey (n=68) of researchers and clinicians involved in MDMA-assisted therapy (MDMA-AT) examines opinions on clinical practices, training, and regulation. The study finds broad support for training standardization and highlights challenges in the national (European) approval process. Experts emphasize the importance of science-informed policy, active regulatory involvement, and international cooperation to integrate MDMA-AT into the European mental healthcare system, particularly for treating PTSD.

Caspani, G., Jefferies, W. A., Netzband, N., Rohani-Shukla, C., Ruffell, S. G. D., Swann, J. R., Tsang, WF.

This review (2024) examines the potential role of the gut microbiome in mediating the effects of psychedelic drugs on behaviour. It argues that the current understanding of psychedelic mechanisms, focused primarily on serotonin 2A receptor agonism, is incomplete and needs to incorporate the gut microbiome and its (two-way) interactions with the brain.

Anderson, B. T., Hendricks, P. S., Johnson, M. O., Mehtani, N. J., Mitchell, J.

This re-analysis (n=12) finds psilocybin-assisted group therapy associated with a significant decrease in HIV-related shame, with a median change of −5.5 points from baseline to 3-months follow-up. However, two participants experienced increased sexual abuse-related shame, raising important considerations for psilocybin therapy in trauma patients.

Corlett, P. R., Doss, M. K., Grimmer, H. J., Hutchinson, B., Laukkonen, R., Lyon, A., McGovern, H., Timmermann, C.

This theoretical review examines how psychedelics may lead to false insights and beliefs by connecting experimental work on false memories with insights under psychedelics using the active inference framework. It suggests that psychedelics increase the quantity and intensity of insights, which could include false beliefs, and proposes future research directions to minimize such risks while maximizing therapeutic potential.

Gallo, J., La Torre, J. T., Mahammadli, M., Williams, M. T., Zalewa, D.

This online, retrospective survey (n=100) of individuals with a history of psychotic experiences and/or diagnoses explores the impact of memorable psychedelic experiences on their well-being and mental health. Most respondents (n=88) reported personal growth, mystical experiences, increased contemplation, improved insight, symptomatic improvements, and positive feelings, while 11% (n=11) described negative experiences such as symptom exacerbation, dysphoria, and terror.

de la Salle, S., Gloeckler, S. G., Greenway, K. T., Lehmann, A., Lucas, P.

This cross-sectional survey (n=2000+) from the Canadian Psychedelic Survey explores the interplay between music and 11 classical and non-classical psychedelic substances in non-clinical settings. It finds most respondents report therapeutic benefits and enjoyment from music during psychedelic use, though benefits vary by substance. Only 10% and 22% support using unfamiliar music and music without understandable lyrics, respectively, suggesting current guidelines may need more nuanced, substance-specific research.

Baraghithy, S., Calles, Y., Gammal, A., Hamad, S., Kočvarová, R., Permyakova, A., Tam, J.

This mouse model study examines the metabolic efficacy of the psychoactive aminoindane derivative MEAI on diet-induced obesity (DIO). MEAI treatment significantly reduced overweight and adiposity, improved glycemic control, decreased hepatic lipid accumulation, increased energy expenditure and fat utilization, and normalized voluntary locomotion without overstimulatory effects, suggesting its potential as a novel therapeutic approach for obesity and related metabolic disorders.

Gasser, P., Holze, F., Liechti, M. E., Müller, F., Strebel, M.

This RCT follow-up study (n=39) investigates the long-term safety and efficacy of LSD-assisted therapy for anxiety (up to 94 weeks out). Participants reported a sustained reduction in anxiety (STAI-G; 33% remission) and depression (BDI; 49% remission) scores, decreased neuroticism, and increased extraversion, attributing positive long-term effects to the psychedelic experience.

Liechti, M. E., Stocker, K.

This commentary on MDMA and MDMA-like substances discusses the terms empathogen (prosocial and empathetic effects) and entactogen (introspective and self-awareness effects). It proposes connectogen as a unified term, highlighting MDMA's ability to create a sense of connection with oneself, others, the present moment, the body, the world, and spiritual principles.

Ahmadkhaniha, R., Amanfo, L., Appelbaum, L. G., Avula, S. G. C., Awan, A., Barksdale, C. T., Berrada, K., Bourne, S., Byard, S., Castledine, R., Cogan, G. B., DeLaRosa, J., Gilbert, J. R., Goldfeder, L., Gould, T. D., Gufford, B. T., Guptill, J. T., Jordan, L., Kennedy, M., Kowalski, K,, Lawrence, Q., Lawson, S., Mack, M., McQuaker, S. J., Moaddel, R., Moore, M. C., Morris, P. J., Oxendine, S., Pao, M., Peterson, M., Quigley, P., Radcliffe, J., Raja, S. M., Rich, N., Sancho, A. R., Thomas, C. J., Twieg, R., Wilmshurst, M., Zanos, P., Zarate, C. A., Zuleta, H.

This Phase I study (n=74) evaluates the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of (2R,6R)-Hydroxynorketamine (RR-HNK) in healthy volunteers. It finds that RR-HNK has a minimal adverse event profile, no serious adverse events, and no anaesthetic or dissociative effects at all doses. The study also reports dose-proportional increases in PK parameters and promising PD outcomes, including gamma power increases in some participants and CNS exposure, supporting progression to Phase II.

Nicol, G. E.

This functional mapping study (n=24) examined brain changes in healthy adults before, during, and up to 3 weeks after taking oral psilocybin (25mg) and methylphenidate (Ritalin), with a follow-up 6+ months later. Psilocybin caused over 3-fold greater acute changes in functional networks than Ritalin, with the most significant disruptions observed in the default mode network (DMN), linked to our sense of self. While a perceptual task reduced these changes, suggesting a way to ground individuals during psychedelic therapy, the acute effects of psilocybin were consistent with distortions of space-time and self. Notably, psilocybin led to a persistent decrease in connectivity between the anterior hippocampus and cortex, especially the DMN, lasting weeks but normalizing after six months, potentially explaining its pro-plasticity and anti-depressant effects.

Carhart-Harris, R. L., Dames, S., de la Salle, S., Erritzoe, D., Garel, N., Gloeckler, S. G., Greenway, K. T., Kettner, H., Lévesque, J. T., Patchett-Marble, R., Rej, S.

This prospective longitudinal survey (n=8) focused on Canadians with Section 56 exemptions for legal psilocybin-assisted psychotherapy. Participants (Mage=52.3, all with cancer) showed significant improvements in anxiety, depression, pain, fear of COVID-19, quality of life, and spiritual well-being two weeks post-treatment. Most found the sessions meaningful but challenging, with one reporting decreased well-being.

Amiri, S., Chehreh, A., Faramarzi, A., Fooladi, M., Khodamoradi, E., Pour, M. Y., Sharin, H., Shavandi, M.

This balanced-order crossover study (n=20) investigates the effects of LSD (75µg) on the pain neural network using fMRI in healthy subjects. The study finds that LSD modulates brain regions involved in pain processing, showing differences in activity and connectivity compared to placebo, and highlights potential implications for future cognitive science and pharmacology research.

Bonnelle, V., Duthaler, U., Feilding, A., Hutten, N. P. W., Kuypers, K. P. C., Liechti, M. E., Mason, N. L., Quaedflieg, C. W. E. M., Ramaekers, J. G., Theunissen, E. L.

This placebo-controlled study (n=53) investigates the effects of repeated low doses of LSD (15μg; 4x) on arousal, attention, and memory. LSD produces stimulatory effects, reducing EEG delta, theta, and alpha power, and enhancing pre-attentive processing, with the strongest effects in individuals with low baseline arousal. Inhibitory effects were observed in high-memory performers. The effects persisted during a 1-week follow-up, suggesting sustained neuroadaptations.

Carhart-Harris, R. L., Erritzoe, D., Nutt, D. J., Roseman, L., Timmermann, C.

This secondary analysis from a DMT study explores the impact of intentional cognitive interruptions on psychedelic experiences. The study investigates whether increasing cognitive load during the experience affects subjective ratings, hypothesizing that higher task demands would lower these ratings. Additionally, it examines whether reduced task demands correlate with larger reductions in long-term depressive symptoms.

Gould, T. D., Greenstein, D., Hess, E. M., Hutchinson, O. L., Zarate, C. A.

This randomised, double-blind, placebo-controlled study (n=68) assesses the prosocial, entactogen effects of ketamine (35mg/70kg) in participants with treatment-resistant depression (TRD). Ketamine increased pleasure from social interactions and helping others, lasting for one week post-treatment. In a rodent experiment, ketamine-treated rats showed increased protective behaviour towards their cage mates, indicating entactogen effects.

Cabral, C., Castelo-Branco, M., Lima, G. M., Pais, M., Rijo, P., Soares, C., Teixeira, M.

This within-subject MRI study (n=11) finds that inhaled DMT increases the mean population receptive field (pRF) sizes in the peripheral visual field of the primary visual cortex (V1). Documented by the Hallucinogen Rating Scale (HRS), this effect explains visual perceptual distortions like field blurring and tunnel vision, and supports the role of 5-HT2A receptor activation in controlling visual cortex activity.

Fortea, A., Fortea, L., Knudsen, G. M., López, F. J. G., Martínez-Ramírez, M., Ona, G., Santamarina, E., Soto-Angona, Ó.

This scoping review (s=27) assesses the relationship between classic psychedelics and seizures. It finds that psychedelics may not increase seizure risk in healthy individuals or animals without other drugs, but concomitant use of substances like kambo or lithium could heighten the risk.

Doss, M. K., Mallaroni, P., Mason, N. L., Ramaekers, J. G.

This re-analysis of an RCT study (n=20) tested the acute effects of psilocybin and 2C-B on the encoding of emotional episodic memories. The study finds that both psychedelics impair estimates of recollection and familiarity, increase familiarity-based false alarms for emotional stimuli, and affect metamemory, indicating a common neurocognitive mechanism across these drugs.

Bagdasarian, F. A., Chen, J., Hansen, H. D., Hooker, J. M., Placzek, M. S., Wey, H-Y., Yoo, C-H.

This fMRI study explores the effects of psilocybin (a serotonergic psychedelic) and Salvinorin-A (a kappa-opioid receptor agonist) on resting-state functional connectivity (FC) in nonhuman primates. It reveals both drugs influence FC around the thalamus, claustrum, prefrontal cortex (PFC), and default mode network (DMN), with similarities and differences noted between them.

Fam, J., Glue, P., Lane, H. Y., Loo, C., Surnam, P., Young, A.

This Phase II clinical trial (n=329) investigated the oral administration of ketamine (extended-release tablet R-107) in adults with treatment-resistant major depression (TRD). The trial demonstrated that R-107 tablets at 180mg exhibited a significant antidepressant effect compared to placebo at 13 weeks (MADRS score -6.1 (n=29).

Beit, C., Blevins, K., Evans, N. G., McGuire, A. L., Neitzke-Spruill, L., Reynolds, J., Robinson, J.

This study (n=26) empirically examines whether psychedelic experiences constitute transformative experiences. Results indicate that psychedelics can lead to significant changes in identity, values, beliefs, desires, and behavior, with 20 participants reporting unique insights and the majority experiencing behavioural changes. Participants felt informed and capable in their decision to use psychedelics, and many reported an enhanced ability to enact changes in their lives.

Alberto-Silva, A. S., Bhatt, M., Bock, H. A., Bossi, E., Brandt, S. D., da Silva, L. A., Hemmer, S., Jäntsch, K., Kastner, N., Kavanagh, P., Kudlacek, O., McCorvy, J. D., Meyer, M. R., Niello, M., Scott, K. R., Sitte, H. H., Stockner, T.

This in vitro and in silico study investigates whether three new methylenedioxy bioisosteres of MDMA improve its off-target profile. Compared with MDMA, these bioisosteres (ODMA, TDMA, and SeDMA) show similar activity at human serotonin, dopamine, and norepinephrine transporters but decreased agonist activity at 5-HT2A/2B/2C receptors and different hepatic metabolism, suggesting potential as safer therapeutic alternatives.

Liknaitzky, P., Polito, V.

This review (2024) critically assesses the available evidence from dose-controlled studies investigating low doses of LSD and psilocybin. It proposes eight potential issues, such as small sample sizes, a limited number of controlled studies, and the possibility of selection bias, that challenge the claims that microdosing is predominantly a placebo effect. It suggests that it is currently inconclusive whether microdosing is merely a placebo.

Friso, F., Harris, M., Politi, M., Vijay, S. L.

This qualitative study (n=11) explores practitioner perspectives on purging during Ayahuasca rituals at the Takiwasi Centre in Peru. Interviews with curanderos, plant preparers, and psychotherapists reveal three main explanatory models: spiritual-oriented, Amazonian-oriented, and clinical-oriented, all emphasizing the interconnectedness of purging and healing in Ayahuasca-assisted treatment for substance dependence.

Anticevic, A., Egan, G. F., Novelli, L., Preller, K. H., Razi, A., Stoliker, D., Vollenweider, F. X.

This secondary (n=24) of an RCT with psilocybin (up to 22mg/70kg) finds that self-inhibition of visual areas of the brain (EVA, FG) leads to complex imagery, as seen by participants. The results align with the REBUS model and highlight (again) how the bottoms-up processes of the brain are amplified under the influence of psychedelics.

Bryan, J. W., Clarke, T. I., Cleary, M. A., Depla, S., Gent, E. M., Holmwood, H. D., Krecké, J., Morgan, C. J. A., Nassereddine, R. O., Salway, C., Statton, S.

This double-blind, pilot study (n=28) investigates esketamine combined with mindfulness-based intervention (MBI) for individuals with alcohol misuse problems. Esketamine enhanced psychological engagement in MBI and transiently decreased alcohol cravings, while also resulting in greater mystical experiences and dissociative states compared to placebo.

Baggott, M., Celidwen, Y., Cohen, I. G., Devenot, N., Gracias, S., Grob, C. S., Harvey, I., Kious, B., Marks, M., McGuire, A. L., Mithoefer, M. C., Nielson, E. M., Öngür, D., Pallas, A., Peterson, A., Schenberg, E. E., Sisti, D., Summergrad, P., Waters, B., Williams, M. T., Yaden, D. B.

This consensus statement (n=27) identifies key ethics and policy issues for integrating psychedelic therapies into clinical practice. It reports 20 points of consensus across 5 ethical issues, with relevant actors responsible for implementation, and highlights areas needing further research and deliberation.

Ballard, E. D., Crainiceanu, C. M., Cui, E., Duncan, W. C., Greenstein, D., Hejazi, N. S., Reiss, P. T., Zarate, C. A.

This secondary analysis of a randomised, double-blind, crossover trial (n=61) evaluates the impact of ketamine on sleep metrics in individuals with treatment-resistant depression (TRD) compared to healthy volunteers (HVs). It finds that while ketamine affects delta and alpha power during sleep, it does not significantly alter sleep macroarchitecture or mediate its antidepressant and anti-suicidal effects through sleep variables.

Cardinale, A. M., Efthimiou, A. A., Kepa, A.

This review evaluates the role of music in psychedelic-assisted therapies (PAT) and indigenous entheogenic ceremonies. It examines neuroscientific, psychological, and anthropological research, highlighting the need for personalized music protocols and the integration of traditional practices into modern treatment models to enhance clinical outcomes.

Bouso, J. C., de Lima Osório, F., Dos Santos, R. G., Guerra, L. T. L., Hallak, J. E., Maekawa, R. M., Paranhos, B. A. P. B., Rodrigues, L. S., Rossi, G. N., Santos, F. P., Yonamine, M.

This single-blind feasibility study (n=11) investigated the effects of one dose of ayahuasca (70ml/70kg) plus psychological support on the drinking patterns of college students with harmful alcohol consumption (mild alcoholism; AUD). A trend towards reduction in alcohol consumption (after statistical correction) was found.

Aday, J. S., Boehnke, K. F., Herberholz, M., Kruger, D. J.

This survey (n=1,221) of psychedelic users assesses attitudes towards altered states of consciousness in psychedelic-assisted psychotherapy (PAP) and the potential of non-hallucinogenic analogues. Most participants (76%) believe altered states are crucial for therapeutic effects, but 61% would try a non-hallucinogenic alternative. Additionally, respondents consider $70-80 per hour a reasonable cost for PAP services, which is below current market rates.

Aday, J. S., Bradley, E. R., Fernandes-Osterhold, G., Horton, D. M., O'Donovan, A., Rosen, R., Woolley, J. D.

This review (2024) scrutinizes the role of psychotherapy in psychedelic-assisted psychotherapy (PAP/PAT) for mental health conditions. It underscores a significant research gap in understanding the psychotherapeutic elements within PAT, despite its assumed importance for safety and efficacy. The paper calls for a transdisciplinary approach in future research to optimize PAT clinical outcomes and inform federal guidelines.

Beer, C., Bhavsar, R., Gonzalez-Velazquez, N., Hahn, M. C, P., Hess, M. R., Jones, N. T., Razidlo, J., Scarlett, C. O., von Salm, J. L., Wenthur, C. J., Witowski, C. G.

This paper outlines the formulation development, in vitro, and in vivo testing of transdermal drug-in-adhesive DMT patches using various adhesives and permeation enhancers. In vivo behavioural and pharmacokinetic studies performed with lead patch formulation (F5) in male and female Swiss Webster mice showed that transdermal administration provided consistent, extended drug release at a non-hallucinogenic dose, with a 77% bioavailability compared to IV at two dosages.

Bouso, J. C., Bruniera, C. P., Cassas, F., de Medeiros, L. S., Dos Santos, R. G., Fonseca, A. M., Hallak, J. E., Paranhos, B. A. P. B., Rodrigues, E., Rossi, G. N., Santos, F. P., Veiga, T. A. M., Yonamine, M.

This observational, cross-sectional study (n=48) investigates the influence of ritualistic ayahuasca consumption on cognition among experienced (n=16) and beginner (n=16) ayahuasca users and a control group (n=16). It finds no evidence of cognitive decline among ayahuasca users, with experienced users showing higher scores in tasks assessing working verbal and visuospatial memories compared to beginners.

Atasoy, S., Cabral, J., Carhart-Harris, R. L., Deco, G., Kringelbach, M. L., Nutt, D. J., Roseman, L., Timmermann, C., Vohryzek, J.

This article (2024) introduces the Harmonic Decomposition of Spacetime (HADES) framework to analyse brain harmonic modes over time. Using this, the effects of DMT on these modes in healthy participants were examined. HADES showed significant changes in low-frequency modes during DMT use, indicating alterations in the brain's functional hierarchy under psychedelics.

Carhart-Harris, R. L., Gazzaley, A., Kettner, H., Pasquini, L., Roseman, L.

This prospective cohort study (n=124, 62 older adults) investigates the effects of a guided psychedelic group session on well-being in older adults (OA) compared to younger adults (YA). Mixed linear regression analyses show significant improvements in well-being in both groups, particularly amplified in OA with a history of psychiatric diagnosis. Acute subjective psychedelic effects were attenuated in OA compared to YA, but a psychosocial measure of Communitas emerged as a predictor in OA, indicating the potential value of relational components in psychedelic group settings for OA.

Casanova, A., Ort, A., Preller, K. H., Seifritz, E., Smallridge, J. W., Vollenweider, F. X.

This double-blind, placebo-controlled study (n=30) investigates the learning effects of psilocybin (up to 20 mg) in a probabilistic cue-reward task with emotional cues. It finds that psilocybin preserves learning effects, is non-inferior to placebo, and suggests higher exploratory behaviour. The 20 mg group showed significantly better learning rates than placebo.

Letheby, C.

This theory-building paper (2024) examines how psychedelic experiences reduce fear of death by promoting non-physicalist metaphysical beliefs. It supports the Relaxed Beliefs Under Psychedelics (REBUS) model over other models of psychedelic therapy and argues that these belief changes undermine the use of psychedelics in naturalizing spirituality within the neuroexistentialist framework.

Alon, A., Barros-Álvarez, X., DiBerto, J. F., Glenn, I. S., Gumpper, R. H., Huang, S., Irwin, J. J., Jain, M. K., Kapolka, N., Kim, K., Kim, Y., Kruse, A. C., Lyu, J., Moroz, M., Roth, B. L., Sakamoto, K., Shoichet, B. K., Skiniotis, G., Tarkhanova, O. O., Tummino, T. A., Wang, L.

This prospective docking study compares the effectiveness of docking large libraries against unrefined AlphaFold2 (AF2) models of σ2 and 5-HT2A receptors with docking against experimental structures. It finds high and similar hit rates and affinities for both AF2 and experimental structures, despite conformational differences in orthosteric residues, and suggests that AF2 models, while differing from experimental structures, are still relevant and effective for structure-based ligand discovery.

Barr, N., Giese, K. J., Moreton, S. G.

This exploratory study (n=155) investigates the relationship between changes in metaphysical beliefs and death anxiety following a significant psychedelic experience. It finds a significant overall reduction in death anxiety, with improvements correlated positively with increased belief in panpsychism, while no other metaphysical beliefs showed a correlation.

Back, A., Guy, J., McGregor, B., Myers, S., Perez, J., Thorn, L. L.

This technical report (2024) describes the evolving guidelines for facilitator use of touch in a group retreat-based format of psilocybin-assisted therapy. The primary goal is to create a safe and supportive haptic experience during sessions, with a secondary goal of maintaining therapeutic boundaries and responding to participant experiences with empathy.

Capper, M. J., Cunningham, M. J., Duggan, P., Havel, V., Kruegel, A. C., Lankri, D., Parise, L. F., Russo, S. J., Sames, D., Serrano, I. C., Wacker, D., Warren, A. L., Zilberg, G.

This molecular study investigates the underpinnings of 5-MeO-DMT pharmacology and its therapeutic potential through cryogenic electron microscopy structures of 5-HT1A, medicinal chemistry, receptor mutagenesis, and mouse behaviour. The research characterizes molecular determinants of 5-HT1A signalling potency, efficacy, and selectivity, contrasting the structural interactions and pharmacology of 5-MeO-DMT with LSD and clinically used 5-HT1A agonists.

Argyri, E. K., Evans, J., Luke, D., McAlpine, R., Michael, P., Michelle, K., Murphy-Beiner, A., Prideaux, E., Robinson, O., Rohani-Shukla, C., Suseelan, S.

This qualitative study (n=26) explored existential distress following psychedelic experiences, finding persistent preoccupation with sense-making and confusion about existence and purpose. Participants reported cognitive, emotional, social, bodily, and functional impacts. They managed distress through embodiment practices and social/cognitive normalization.

Darer, J. D., Harding, L., Joshi, K., Liberman, J. N., Parab, P.

This retrospective observational cohort study (n=966 esketamine initiators, n=39,219 controls) examines factors influencing esketamine initiation and continuation for treatment-resistant depression (TRD). Initiators resided closer to treatment centres, with initiation rates decreasing significantly with distance. Factors associated with increased initiation included posttraumatic stress disorder, suicidal ideation, and male sex, while Medicaid, substance use disorder, older age, and greater distance were associated with lower initiation rates.

Claesdotter-Knutsson, E., Kajonius, P. J., Sjöström, D. K.

This cross-sectional study (n=400 psychedelic users, matched with non-users) explores the mental health and personality characteristics of Swedish individuals with psychedelic experiences. Results indicate that psychedelic users exhibit lower depression levels (PHQ-9) and higher drug use (DUDIT), with openness (Big Five) being notably different (d=1.72), contributing to the observed effects on depression. The findings suggest potential implications for understanding and approaching psychedelic users in the context of mental health and personality traits.

Black, J. C., Dart, R. C., Dasgupta, N., Jewell, J. S., Monte, A. A., Olson, R. A., Rockhill, K. M.

This commentary (2024) highlights the promising results from late-phase clinical trials on psychedelic-assisted psychotherapy, suggesting imminent FDA approval and wider adoption in the USA. However, it emphasizes the crucial need for postmarket surveillance to ensure real-world benefits are maximized, and potential risks are mitigated. Without proper surveillance, there's a risk of incorrect conclusions, such as attributing adverse events to illicit psychedelics. Effective surveillance programs should monitor access, safety, and effectiveness across various domains, but current data systems are inadequate, necessitating intentionally designed surveillance mechanisms.

Aepfelbacher, J., Panny, B., Price, R.

This randomised controlled trial (n=116) investigated the psychological mechanisms of ketamine's antidepressant effects. Participants receiving ketamine reported significantly heightened feelings of awe compared to those receiving a placebo. Awe experiences, as measured by the Awe Experience Scale (AWE-S), mediated depression outcomes (% improvement in MADRS scores) at multiple time points (24 hours and 5, 12, 21, and 30 days) post-infusion, indicating a potential role of awe in ketamine's therapeutic efficacy for depression.

Carhart-Harris, R. L., Deco, G., Kringelbach, M. L., Luppi, A. I., Lynn, C., Muthukumaraswamy, S., Nutt, D. J., Roseman, L., Shinozuka, K., Sicignano, D. J., Tewarie, P. K. B.

This pre-print brain imaging study (n=16, MEG) investigates the neural effects of psychedelics, focusing on hierarchy based on directed functional connectivity (FC). Administering LSD to healthy participants, researchers find LSD diminishes the asymmetry of directed connectivity over time and enhances machine learning classifiers' accuracy in distinguishing LSD from placebo based on hierarchy metrics. These findings suggest LSD weakens the brain's directed connectivity hierarchy by balancing neural signal senders and receivers.

Carhart-Harris, R. L., Carrithers, B. M., Gordon, A. R., Kettner, H., Marrocu, A., Nayak, S., Pagni, B. A., Roberts, D. E., Weiss, B., Zeifman, R. J.

This pre-print prospective observational study (n=21) followed individuals with personality disorders (PDs) before, 2 weeks, and 4 weeks after psychedelic use. Another study (n=55) observed individuals with PDs before, 2-4 weeks, and 2-3 months after psychedelic use. Results indicate reductions in suicidal ideation (6.67%) and improvements in anxiety and depression symptoms, though some experienced increased anxiety and depression severity.

Argento, E., Brendle, M., Girn, M., Jaeger, A., Lewis, E. C., Omene, E.

This conceptual synthesis proposes psychedelic-assisted therapy (PAT) as a potential treatment for functional seizures (FS), a subtype of functional neurological disorder (FND). Drawing on empirical evidence and complexity science, the argument is constructed for the potential efficacy of PAT in treating FS, highlighting FS as a cohort to investigate neural mechanisms of PAT. The synthesis also outlines a novel analytic roadmap to identify markers of FS diagnostic specificity and treatment success, aiming to bridge clinical neurology with psychedelic medicine and establish a new field of psychedelic neurology.

Bedi, G., Carter, O., Colcott, J., Guerin, A. A., Meikle, S.

This systematic review and meta-analysis (2024) examined the side effects of MDMA-assisted psychotherapy (MDMA-AP) across Phase II and III studies. Thirteen studies were included, with most showing an increase in side effects during medication sessions and the following week compared to control conditions. Despite these findings, the overall certainty of evidence was rated as very low to moderate, and the quality of side effects reporting was generally poor, suggesting further research is needed to fully understand the safety profile of MDMA-AP.

Kuypers, K. P. C., Ramaekers, J. G., Sorger, B., Tipado, Z.

This theory building (2024) elucidates a new understanding of psychedelic modulation in the retinofugal pathway (between the eye and primary visual cortex). It suggests that disruptions in communication between cortical and subcortical regions, influenced by serotonin receptors, may lead to perceptual alterations and hallucinations.

Baumgartner, M. R., Beste, C., Cole, D. M., Friedli, N., Opitz, A., Quednow, B. B., Steuer, A. E., Stock, A-K., Verdejo-Garcia, A., Zacher, A., Zimmermann, J.

This comparative study (n=165) evaluated social cognitive functions and behaviors in chronic METH users, chronic MDMA users, and stimulant-naïve controls. METH users exhibited diminished cognitive and emotional empathy towards positive stimuli, elevated punitive social behavior regardless of provocation, and heightened trait anger. MDMA users showed a distinct rise in punitive behavior when provoked, with correlations suggesting associations between substance use patterns and social-cognitive deficits.

Bershad, A. K., de Wit, H., Haggarty, C. J., Kumar, M. K., Lee, R.

This EEG study (n=25) investigated the effects of MDMA (100mg) and methamphetamine (MA) on early visual processing of socio-emotional stimuli. MDMA enhanced the N170 component, sensitive to detecting faces, particularly for happy and angry expressions compared to neutral faces, while MA did not show similar effects.

D’Souza, D. C., Guss, J., Krause, R., Pathania, S., Pittman, B. P., Safi-Aghdam, H., Sloshower, J. A., Zeifman, R. J.

This re-analysis of a single-blind, placebo-controlled study (n=19) of psilocybin (21mg/70kg) in combination with therapy (ACT, 8x) finds that psychological flexibility, mindfulness, and living according to one's values improved after psilocybin and stayed better through the 16-week study period. It also shows that greater psychological flexibility and experiential acceptance were linked with lower depression scores after psilocybin.

Adkinson, B., Anticevic, A., Burt, J. B., Camarro, T., Cho, Y., Diehl, C., Fineberg, S. K., Flynn, M., Fonteneau, C., Ji, J. L., Kolobaric, A., Krystal, J. H., Morgan, P. T., Moujaes, F. F., Murray, J. D., Preller, K. H., Rahmati, M., Repovs, G., Rieser, N. M., Santamauro, N., Savic, A., Schleifer, C., Seifritz, E., Tamayo, Z., Vollenweider, F. X., Xu, J.

This single-blind placebo-controlled study (n=40) investigated the neural and behavioral effects of acute ketamine in healthy participants. Results revealed robust inter-individual variability in both neural and behavioral responses to ketamine, with data-driven individual symptom variation mapping onto distinct neural gradients. These findings emphasize the need to consider individual variation in response to ketamine and suggest potential implications for developing precise pharmacological biomarkers in psychiatry.

Aicher, H. D., Bauer, P. R., Ehrenkranz, R., Funk, X., Graziosi, M., Meling, D., Nayak, S., Scheidegger, M., van Elk, M., Yaden, D. B.

This commentary (2024) provides an evidence-informed assessment of psychedelic research for treating depression. It discusses the shift in media reporting from overstating the risks to overly positive hype and emphasizes the need for clear science communication to set public expectations and inform policy decisions accurately.

Chelu, V., Graesser, L., Juliani, A., Safron, A.

This pre-print, based on predictive processing and an energy-based model of cortical dynamics, explores the therapeutic mechanism of serotonergic psychedelics. It suggests that a combination of 5-HT2a and 5-HT1a agonism leads to a more psychologically tolerable acute experience and better therapeutic efficacy compared to pure agonists. This finding supports the clinical success of mixed serotonin agonists like LSD, psilocybin, and DMT, and suggests potential for the development of even more effective and tolerable psychotherapeutic agents, such as biased 5-HT1a agonist psychedelics like 5-MeO-DMT.

Dunbar, F., Ermakova, A. O., Roberts, C. A., Rucker, J., Seynaeve, M., Suttle, B., Wiegand, F., Yamamoto, T., Young, A. H.

This double-blind, placebo-controlled study (n=44) examines the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of BPL-003, a novel intranasal benzoate salt formulation of 5-MeO-DMT (up to 12mg), in healthy participants. BPL-003 was well tolerated, showing rapid absorption and elimination.

Barba, T., Carhart-Harris, R. L., Erritzoe, D., Greenway, K. T., Marguilho, M., Peill, J. M., Rosas, F. E., Timmermann, C.

This re-analysis of an RCT (n=59) examines the concept of an 'inner healer' effect associated with psilocybin. Participants receiving a high dose of psilocybin (25mg, 2x) reported higher inner healer scores compared to those receiving a placebo (escitalopram). Furthermore, higher inner healer scores in the high-dose group correlated with improved depressive symptoms two weeks post-dosing, suggesting a potential therapeutic mechanism.

Tacla, C., Tap. S. C.

This review (2024) examines the potential therapeutic mechanisms of action for alcoholism (AUD) treatment using 5-MeO-DMT. It highlights that 5-MeO-DMT can induce mystical experiences and ego-dissolution, leading to increased psychological flexibility and mindfulness, which may alleviate AUD symptoms. Additionally, preliminary evidence suggests that 5-MeO-DMT modulates neural oscillations and exhibits neuroplasticity and anti-inflammatory properties, indicating its potential clinical implications for AUD and related psychiatric comorbidities.

Bola, M., Hobot, J., Orłowski, P., Ruban, A., Szczypiński, J.

This cross-sectional study (n=113) compared experienced psychedelic users (n=56) to nonusers (n=57) regarding neural responses to Self-name stimuli, known for activating self-representation. While no difference in P300 amplitude was found between users and nonusers for Self- or Target-names, users exhibited increased P300 amplitude for Other-names. Additionally, users showed a smaller increase in P300 amplitude for task-relevant stimuli compared to nonusers, suggesting potential alterations in attentional resource allocation rather than prolonged changes in self-representation due to psychedelic use.

Demertzi, A., Fort, L. D., Mallaroni, P., Mason, N. L., Mortaheb, S., Ramaekers, J. G.

This pre-print neuroimaging study (n=49) compared psilocybin and placebo effects on brain patterns and subjective experiences using ultra-high field 7T MRI. Participants who took psilocybin (12mg/70kg, n=22) displayed increased average functional connectivity and a hyperconnected-hyperarousal brain pattern, correlated with profound changes in consciousness, notably feelings of oceanic boundlessness and visionary restructuralization, as measured by the 5D-ASC Rating Scale. This study links these brain dynamics to the phenomenological experiences during the psychedelic state for the first time.

Cozzi, N. V., D’Souza, D. C., Flynn, L. T., Gottschalk, C. H., Pittman, B. P., Schindler, E. A. D., Sewell, R. A., Zhu, Y.

This double-blind, placebo-controlled study (n=10) assesses the safety and efficacy of repeated pulse administration of psilocybin (10mg/70kg, 3x in 15 days) in cluster headache patients. Following the initial trial, eligible participants received a psilocybin pulse at least 6 months later and kept headache diaries for 8 weeks. Results indicate a significant reduction in cluster attack frequency following the psilocybin pulse, suggesting potential therapeutic benefits.

Allen, N., Evans, W. J., Forsyth, A., Hoeh, N. R., Jeremiah, A., Menkes, D. B., Murphy, R., Muthukumaraswamy, S., Roop, P., Sumner, R. L., Sundram, F.

This Phase I RCT (n=80) examined the effects of microdosing LSD (10μcg; 14x; 6w) on sleep in healthy adult male volunteers, with doses self-administered every third day and sleep monitored through a commercially available sleep/activity tracker. The results showed that participants in the LSD group slept an extra 24.3 minutes per night on the night after microdosing compared to the placebo group, with no changes in sleep stages or physical activity.

Earleywine, M., MacConnel, H. A., Radowitz, S.

This pre-print open-label trial (n=117) administered intravenous ketamine in highly supportive environments to outpatients with elevated PTSD symptoms. The protocol included preparatory, integration, sensory immersion, and psychotherapy sessions, resulting in significant reductions in PTSD symptoms. The study highlights the potential of ketamine when delivered in a psychedelic therapy paradigm, suggesting it as a promising option for PTSD treatment resistant to other therapies.

Admon, R., Gross, R., Magal, N., Netzer, O., Polinsky, T., Salomon, R., Stern, Y.

This retrospective cohort study (n=657) examines the acute experiences and peritraumatic processing of survivors from a high-casualty terror attack, with approximately two-thirds under the influence of psychoactive substances. Those who experienced the trauma under MDMA showed improved intermediate outcomes, including increased social support, more interactions, and better sleep quality, leading to reduced mental distress and PTSD symptom severity. These findings suggest a potential protective effect of MDMA during trauma.

Dörner, S., Hoffmeister, D., Hudspeth, J., Müll, M., Rogge, K., Rupp, B., Werten, S.

This structural study delves into the mechanism of PsiM, the enzyme responsible for the final step in psilocybin biosynthesis. The researchers present high-resolution crystal structures of PsiM, revealing insights into its methylation mechanism. They also propose that PsiM shares evolutionary origins with N6-methyladenosine writers, highlighting its potential for bioengineering to enhance psilocybin's therapeutic benefits.

Berit, S., Dornbierer, D. A., Hirsch-Hoffmann, M., Kometer, M., Meling, D., Michels, L., Scheidegger, M., Seifritz, E., Smigielski, L., Vollenweider, F. X.

This placebo-controlled study (n=36) investigated fMRI data from experienced meditators undergoing focused attention and open monitoring meditation before and after a five-day psilocybin-assisted (22mg/70kg on day 4) meditation retreat. Psilocybin-induced positive derealization, coupled with enhanced open-monitoring meditation, correlated with the optimal transport distance between open monitoring and resting state. This suggests that enhanced meta-awareness through meditation combined with psilocybin may mediate insightfulness, offering potential novel brain markers for positive synergistic effects between mindfulness practices and psychedelics.

aan Het Rot, M., Kamphuis, J., Schoevers, R. A., Smith-Apeldoorn, S. Y., Spijker, J., van Asselt, A. D. I., van der Meij, A., Veraart, J. K. E.

This randomised placebo-controlled trial (n=111) investigated the efficacy, safety, and tolerability of fixed low-dose oral esketamine (3x p/d 42d; 30-90mg; oral) in patients with treatment-resistant depression (TRD). Results indicate that fixed low-dose oral esketamine did not show benefit on depressive symptom severity compared to placebo, but individually titrated higher doses in the open-label extension phase demonstrated potential antidepressant properties.

Adank, A., Bankwitz, A., Brühl, A. B., Colla, M., Eicher, C., Kronenberg, G., Mikoteit, T., Mutschler, J., Offenhammer, B., Schaekel, L., Scheerer, H., Seifritz, E., Vetter, S.

This double-blind, randomised study (n=27) assessed the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in TRD patients as add-on therapy. Patients received either 160 mg/day or 240 mg/day KET01 or placebo for 14 days, with the primary endpoint being the change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. Results suggest a positive trend towards antidepressant efficacy with 240 mg/day KET01.

Barba, T., Carhart-Harris, R. L., Erritzoe, D., Nutt, D. J., Rosas, F. E., Spriggs, M. J.

This post hoc analysis of a recent clinical trial comparing psilocybin to escitalopram with psychological support for depression (MDD) found that discontinuing SSRIs/SNRIs prior to psilocybin treatment led to reduced treatment effects on depression severity measures. However, there were no observed effects on the acute psychedelic experience. The study suggests that discontinuation of SSRIs/SNRIs before psilocybin treatment might impact treatment response.

Belgers, M., Heine, R. T., Heydari, P., Knuijver, T., Kramers, C., Lucas, L., Schellekens, A., van Oosteren, T., Verkes, R. J., Westra, S.

This pharmacokinetic study (n=14) on ibogaine (700mg/70kg) for opioid use disorder (OUD) finds significant variability in ibogaine clearance, strongly correlated with CYP2D6 genotype. Ibogaine plasma concentrations correlate with QTc prolongation and cerebellar effects, while neither ibogaine nor noribogaine correlate with the severity of opioid withdrawal symptoms.

Gutierrez, G., Kang, M. J. Y., Vasquez, G.

This longitudinal study (n=71) examines five years of real-world clinical data on the use of IV low-dose ketamine alongside standard care for outpatients with depression (MDD & TRD). Results indicate a significant reduction in depressive symptoms and suicide ideation by treatment endpoint, with 55% of patients responding to treatment. Side effects were transient and mild for 78% of patients, with a dropout rate of 11%. Multivariate analysis suggests that demographic variables did not impact treatment efficacy or tolerability.

Bon, J., Elersič, K., Hudnik, L. K., Levačić, A., Oblak, A., Pregelj, P.

This pre-print (n=13) investigates the subjective experiences of individuals engaging in psilocybin microdosing in their daily lives. Combining momentary ecological assessments and retrospective interviews, participants reported varied effects, including loosening of mental structures, increased salience of external stimuli, flexible cognition, and ego-dystonic contents.

Becker, A. M., Halter, N., Holze, F., Ley, L., Liechti, M. E., Straumann, I.

This pooled analysis (n=85; doses=113) of three randomised crossover studies evaluates the safety pharmacology of psilocybin (15-30mg). Psilocybin induced stronger effects at higher doses, with 25 mg and 30 mg doses showing increased anxiety. However, overall, psilocybin was found to be safe in terms of acute psychological and physical harm, with no serious adverse reactions reported, suggesting its potential safety for controlled research settings.

Jylkkä, J.

This philosophical article (2024) discusses the compatibility of mystical-type experiences induced by psychedelic substances with naturalism. The author suggests that while mystical insights may align with naturalism by considering the ultimate nature of reality as observation-independent, accessing the fundamental nature of all reality remains a challenging hard problem. Psychedelics are proposed to enhance awareness of consciousness and the limitations of our reality models, but it is unclear if they provide access to the fundamental nature of all reality. In conclusion, the author contends that mystical-type conceptions about reality may coexist with naturalism but are generally unverifiable, similar to many metaphysical theses.

Barrett, F. S., Davis, A. K., Griffiths, R. R., Gukasyan, N., Lancelotta, R., Levin, A. W., Nayak, S., Sepeda, N. D., Wagener, T. L.

This randomised, waiting list-controlled clinical trial (n=24) for depression (MDD) assessed the therapeutic alliance between participants and intervention facilitators in psilocybin-assisted therapy (PAT). Therapeutic alliance significantly increased from the final preparation session to one-week post-intervention, with a stronger alliance predicting depression scores at various post-intervention time points. Stronger alliances were correlated with peak ratings of mystical experiences and psychological insight, which in turn were correlated with depression scores.

Berzosa, X., Camarasa, J., Escubedo, E., Estrada-Tejedor, R., Holy, M., Islam, M. N., Ketsela, G., López-Arnau, R., Nadal-Gratacós, N., Niello, M., Pubill, D., Puigseslloses, P., Sitte, H. H., Weiss, N.

This cell & mice study explores the psychopharmacological profile of amino-substituted 5-MeO-tryptamines, focusing on their interactions with serotonin receptors and transporters, as well as their psychoactive and thermoregulatory properties. The study demonstrates selectivity for 5-HT1AR over 5-HT2AR among examined compounds using radioligand binding methodologies and computational docking analyses, and 5-MeO-pyr-T was identified as the most potent partial 5-HT releaser.

Larsson, H., Lu, Y., Mosing, M. A., Osika, W., Simonsson, O., Ullén, F., Wesseldijk, L. W.

This observational study (n=16.255) investigates the association between naturalistic psychedelic use and self-reported psychotic or manic symptoms in adolescents, utilizing a genetically informative design. Results suggest that psychedelic use may be associated with reduced psychotic symptoms after adjusting for other drug use, while associations with manic symptoms seem to be linked to genetic vulnerability to schizophrenia or bipolar I disorder.

Allen, L. R., Gold, V., Luoma, J. B., Stauffer, C.

This literature review examines the role of therapeutic touch in MDMA-assisted therapy (MDMA-AT), addressing concerns about power imbalances and ethical boundaries. It introduces the Touch Outcomes Measurement Inventory (TOMI) to assess client perceptions of touch in MDMA-AT, emphasizing the need for evidence-based and ethical guidelines in psychedelic-assisted therapy.

Falkenberg, I., Hofmann, S. G., Kircher, T., Matsingos, A., Noor, L., Rief, W., Wilhelm, M., Yildiz, C.

This meta-analysis (n=1100; s=14) of clinical trials on patients with depression (MDD) receiving ketamine or esketamine reveals a substantial placebo response, accounting for up to 72% of the overall treatment response. The study emphasizes the importance of considering the placebo response in clinical practice to maximize the benefit to patients.

Carhart-Harris, R. L., Erritzoe, D., Giribaldi, B., Nutt, D. J., Roseman, L., Weiss, B.

This secondary of a trial (n=59) investigates the mechanisms underlying the efficacy of Psilocybin Therapy (PAT) versus Escitalopram Treatment in patients with depression (MDD) over a 6-week trial period. Acute psychological experiences such as mystical experience and ego dissolution were found to mediate the effect of treatment condition on depressive response, suggesting a mechanistic role of these experiences in the treatment of depression via PAT.

Brulin, J. G., Cherniak, A. D., Granqvist, P., Mikulincer, M.

This survey (n=185) of an international Jewish sample with psychedelic experience explores the association between attachment-related variables and psychedelic experiences. Findings suggest that perceptions of an insecure attachment history are positively linked to various measures of psychedelic phenomenology, while adult attachment orientations show no significant relationship. Moreover, psychedelic experiences do not typically moderate the association between perceived insecure attachment history and present attachment insecurity.

Carhart-Harris, R. L., Erritzoe, D., Kettner, H., Marrocu, A., Weiss, B., Zeifman, R. J.

This prospective observational study (n=807) analysed negative psychological responses to psychedelics, defining it as a clinically meaningful decline in mental health four weeks post-use. They found that 16% of participants experienced negative responses, with a notably higher prevalence (31%) among those with a prior diagnosis of personality disorder. The study implies that individuals with a history of personality disorder might face elevated risks with psychedelic use, emphasizing the need for enhanced psychological support and therapeutic alliance in this population.

Baumgartner, M. R., Beste, C., Cole, D. M., Coray, R., Opitz, A., Pilhatsch, M., Quednow, B. B., Steuer, A. E., Stock, A-K., Zachäi, A., Zimmermann, J.

This comparative study (n=38 METH users, n=42 MDMA users, n=83 controls) examines the impact of chronic METH and MDMA use on conflict control processes in social-affective contexts. Both METH and MDMA users exhibit reduced behavioral effects in cognitive-emotional conflict processing, particularly regarding anger content. These effects are associated with stronger P3 event-related potential modulations, suggesting altered decision-making and stimulus-response mapping, potentially linked to noradrenergic dysfunctions. Understanding the role of noradrenaline in chronic users of substituted amphetamines represents a significant direction for future research in this area.

Cassidy, K., D'Andrea, W., Healy, C. J., Henje, E.

This observational study (n=231) examines the relationship between childhood trauma, challenging experiences during acute ayahuasca effects, and posttraumatic growth. Results show that individuals with histories of childhood trauma were not at higher risk of adverse experiences during ayahuasca use, nor did they exhibit different levels of posttraumatic growth compared to those without such histories. Additionally, experiencing more challenges during acute ayahuasca effects did not correlate with increased posttraumatic growth.

Carhart-Harris, R. L., Copa, D., Erritzoe, D., Giribaldi, B., Nutt, D. J., Tagliazucchi, E.

This machine learning study (n=16) examines baseline resting-state functional connectivity (FC) measured with fMRI as a predictor of symptom severity in psilocybin-assisted therapy for treatment-resistant depression (TRD). Results show that FC of visual, default mode, and executive networks predicted early symptom improvement, with the salience network predicting responders up to 24 weeks after treatment.

Aday, J. S., Bloesch, E. K., Davis, A. K., Davoli, C. C., Domoff, S. E., Scherr, K., Woolley, J. D.

This open-label longitudinal study (n=54) explores the impact of ayahuasca on aesthetic experiences, measured before and after attending an ayahuasca retreat. The findings suggest an increase in aesthetic experiences following the retreat, despite no correlation between measures of acute drug effects (e.g. intensity of the trip) and changes in aesthetic experience.

Heifets, B. D., Szigeti, B.

This review (2024) explores the impact of participant expectations on psychedelic clinical trials. It highlights the challenge of maintaining blinding as doses increase and discusses the potential bias introduced by positive expectancy. The review covers expectancy effects in both micro- and macrodose trials, suggesting that understanding and managing expectancy could enhance trial rigour and treatment outcomes in future psychedelic research.

Carhart-Harris, R. L., Gallen, C. L., Gazzaley, A., Kettner, H., Pasquini, L., Roseman, L., Simon, A. J., Timmermann, C.

This pre-print single-blind study (n=14) used multimodal neuroimaging techniques (fMRI + EKG) to investigate brain activity and autonomic physiology during DMT (20mg) altered state of consciousness. Results reveal unique brain activity substates, with increased superior temporal lobe activity and hippocampal deactivation under DMT, correlating with auditory distortions and meaningfulness of the experience, respectively. Moreover, increased heart rate under DMT correlates with hippocampal and medial parietal deactivation, suggesting a potential link between sympathetic regulation and positive mental health outcomes following psychedelic administration.

Cabral, J., Carhart-Harris, R. L., Deco, G., Fernandes, H. M., Kringelbach, M. L., Lord, L-D., Nutt, D. J., Roseman, L., Vohryzek, J.

This fMRI study (n=15) reanalysed data from a previous open-label study in which psilocybin (10-25mg) was used in the treatment of depression (TRD). After using whole-brain models to fit the spatiotemporal brain dynamics, dynamic sensitivity analysis identified brain regions in transition from a depressive brain state to a healthy one. The identified regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, providing further evidence for the role of serotonergic signalling in the recovery of depression via psilocybin.

Aicher, H. D., Gasser, P., Schmid, Y.

This commentary (2024) provides insights into the current practice of psychedelics-assisted therapy (PAT) in Switzerland, based on legally permitted medical use since 2014. Over 1000 individual case permits have been issued, allowing approximately 2000-3000 treatments. The article discusses application procedures, treatment frameworks, and ethical considerations, highlighting the potential for integrating PAT into psychotherapy internationally while emphasizing the need for ongoing therapist education and quality assurance measures.

Abate, A., Ali, S., Bawks, J., Blainey, M. G., Brietzke, E., Brudner, R. M., Cronin, V., Danielewitz, J., Dhawan, S., Di Fonzo, M., Doyle, Z., Drzadzewski, P., Dunlop, W., Fiszter, H., Gomes, F. A., Grewal, S., Kaczmarek, E., Kratiuk, K., Leon-Carlyle, M., Mansur, R. B., Marlborough, M., McCallum, M., McIntyre, R. S., Meshkat, S., Mofidi, N., Offman, H., Quinn, J. M., Riva-Cambrin, J., Schmidt, J., Schulz-Quach, C., Sethi, R., Smolkin, M., Zumrova, A.

This open-label waitlist trial (n=30) assessed the feasibility of psilocybin-assisted psychotherapy (PAP/PAT) in a complex population with treatment-resistant depression (TRD), including major depressive and bipolar II disorders, baseline suicidality, and significant comorbidity. Participants received one, two, or three sessions of PAP with psilocybin (25mg), accompanied by preparation and integration psychotherapy sessions. Immediate treatment showed greater reductions in depression severity (MADRS) compared to the waitlist period, with a large effect size (g = 1.07, p < 0.01). Repeated doses were associated with further reductions in depression severity. Adverse events were transient, and the study demonstrated feasibility, preliminary antidepressant efficacy, safety, and tolerability in this population.

Haijen, E. C. H. M., Hurks, P. P. M., Kuypers, K. P. C.

This prospective survey (n=233, 64, 44) explores microdosing's (MD) impact on emotional regulation (ER) and empathy in adults with severe ADHD symptoms. Positive effects on ER and empathy were observed, specifically in cognitive reappraisal, expressive suppression, perspective-taking, and personal distress. However, a comparison with those using only conventional medications (n=180, 50, 38 MD; n=37, 27, 28 conventional) revealed that after four weeks, only expressive suppression improvement persisted, and cognitive reappraisal and empathy enhancements disappeared.

Acevedo, E. C., Al-Shawaf, L., Uhler, S., White, K.

This analysis (n=240) of online trip reports examines the mechanisms behind the therapeutic potential of psychedelics, comparing metaphysical belief theory and predictive self-binding theory. Path analysis and structural equation modelling reveal that psychological insight, rather than metaphysical beliefs, uniquely predicts beneficial outcomes. Additionally, the positive effects of ego dissolution and therapeutic intent on beneficial outcomes are fully mediated by psychological insight, thereby supporting the predictive self-binding model over the metaphysical belief theory.

Elmer, T., Lyubomirsky, S., Studerus, E., Vannoy, T. K.

This survey study (n=766) explores the consumption habits and perceived long-term social-emotional effects of MDMA use among individuals aged 18-61, primarily from Western countries. Utilizing a K-medoids clustering algorithm, researchers identified three consumption setting types-party settings with friends (n=388), private home settings (n=132), and mixed settings (n=246)-and three intention types-euphoria and energy (n=302), self-insight (n=219), and mixed intentions (n=245). The study found that individuals in the self-insight and mixed intentions clusters reported more long-term socio-emotional benefits compared to those seeking solely euphoria and energy, with no significant differences observed between the setting clusters.

Carhart-Harris, R. L., Castro-Rodrigues, P., Erritzoe, D., Godfrey, K., Nutt, D. J., Peill, J. M., Timmermann, C., Wall, M. B.

This review (2024) discusses the pivotal role of neuroimaging in modern psychedelic research, providing insights into the acute and longer-term therapeutic effects of these substances. Evidence from fMRI, PET, and MEG/EEG studies informs computational models, offering a comprehensive understanding of the effects of psychedelics on human consciousness as well as supporting the advancement of psychedelic therapies.

Agnorelli, C., Erritzoe, D., Fagiolini, A., Faraji, S., Nogueira, J. J., Nutt, D. J., Palmisano, V. F.

This computational study investigates the membrane permeability of 12 selected tryptamines, aiming to elucidate the impact of various structural modifications on their permeation behaviour. Using classical molecular dynamics simulations and umbrella sampling techniques, the study finds that dimethylation of the primary amine group and methoxy substitution at position 5 increase permeability, while positional substitutions on the indole groups and protonation decrease permeability.

Bogenschutz, M. P., Claus, E. D., Grinband, J., Pagni, B. A., Petridis, P. D., Podrebarac, S. K.

This secondary of a Phase II study (n=11) investigated psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder (AUD). Participants received psilocybin (25mg; n=5) or diphenhydramine (antihistamine; 50mg; n=6). Psilocybin increased activity in the medial and lateral prefrontal cortex and left caudate, while decreasing activity in several other brain regions. These findings suggest enhanced goal-directed action, improved emotional regulation, and diminished craving.

Barba, T., Carhart-Harris, R. L., Erritzoe, D., Giribaldi, B., Kettner, H., Nutt, D. J., Peill, J. M., Radu, C., Roseman, L.

This mixed-methods study combines data from two studies, one large naturalistic study (n=261) and one smaller controlled clinical trial (n=59), to investigate the post-acute effects of psychedelics on self-reported sexual functioning. It finds that naturalistic use of psychedelics is associated with improvements in sexual pleasure, communication, satisfaction with one’s partner, and physical appearance. Similarly, a controlled trial comparing psilocybin therapy with the SSRI escitalopram for depression shows that patients treated with psilocybin report positive changes in sexual functioning, unlike those treated with escitalopram.

Kelmendi, B., Mandell, B., Rowland, R. S., Schmidt, E. F., Stogniew, M., Warner-Schmidt, J.

This preclinical study (in cells) investigated methylone's potential for treating PTSD, comparing it with MDMA. Methylone showed rapid antidepressant and anxiolytic effects in preclinical models, affecting gene expression related to neuroplasticity in brain areas associated with PTSD and MDD. Unlike MDMA, methylone demonstrated no off-target effects at various receptors, indicating potential higher specificity, and suggesting its potential use in treating PTSD and other neuropsychiatric disorders.

Carhart-Harris, R. L., Erritzoe, D., Nutt, D. J., Timmermann, C., Zeifman, R. J.

This placebo-controlled trial (n=13) and prospective study (n=17) examine the effects of DMT (iv) on mental health outcomes in healthy volunteers. Significant improvements in depression scores are observed 1-2 weeks after DMT administration in both datasets, with reductions in trait Neuroticism found only in the placebo-controlled sample. Correlations between acute peak experiences and changes in depression and trait anxiety are noted.

Aycart, J. M., Jones, L. S., Kuhn, T., Rabin, D. M., Swanson, L. N., Zhu, Z.

This retrospective analysis (n=431) of at-home ketamine treatments (1x p/w, 50-400mg lozenges) for depression, generalized anxiety, and social anxiety found statistically significant improvements in symptoms measured via PHQ-9, GAD-7, and SAD-D-10 at all follow-up time points (1-2-3 months). Minor side effects were reported by 18.8% of patients, resolving within 24 hours, and the majority concluded treatment within ≤ 6 months. No significant differences were observed between treatment-resistant and non-resistant depression outcomes.

Breeksema, J. J., Kamphuis, J., Karsten, T., Krediet, E., Niemeijer, A. R., Schoevers, R. A., van den Brink, W., Vermetten, E.

This qualitative study (n=11) explores the experiences of treatment-resistant depression (TRD) patients undergoing a double-blind, randomised clinical trial with a single session of oral psilocybin treatment (1, 10, or 25 mg). Three major themes emerged: trust-building and expectation management challenges, navigating the experience, and the need for a more comprehensive treatment. Subthemes included distrust in mental healthcare, managing expectations, profound experiences during the session, and a desire for multiple psilocybin sessions. Insights from patients' perspectives suggest strategies for optimizing psilocybin treatment for TRD, such as individualized preparation, trust-building, additional sessions, and personalized therapy approaches.

Godfrey, K., Murphy, R. J., Muthukumaraswamy, S., Shaw, A. D., Sumner, R. L.

This randomised controlled trial (n=80) investigated the effects of microdosed LSD (10µg; 14x) on neural plasticity using a visual long-term potentiation (LTP) EEG paradigm. Participants received either LSD or placebo and completed the visual LTP paradigm both acutely and after six weeks of repeated microdosing. While event-related potential (ERP) analyses didn't show changes in visually induced LTP, dynamic causal modelling revealed alterations in laminar connectivity in the primary visual cortex, suggesting a more sensitive approach to assessing neural plasticity compared to traditional peak analysis methods.

Aday, J. S., Bloesch, E. K., Davis, A. K., Davoli, C. C., Domoff, S. E., Scherr, K., Woolley, J. D.

This longitudinal study (n=54) investigates the effects of ayahuasca retreat experiences on gratitude, nature relatedness, and nature appreciation. Findings reveal significant increases in these factors at one-week and one-month follow-ups compared to baseline. Ratings of mystical experiences and awe during ayahuasca sessions weakly-to-moderately correlate with these increases, highlighting their potential role in post-ayahuasca changes. Participant age negatively relates to the occurrence of mystical experiences and awe, indicating diminished effects with increased age. The study emphasizes the quality of experiences over quantity in influencing post-ayahuasca changes, suggesting potential mental health benefits associated with prosocial changes in gratitude and nature relationships.

Bayes, A., Brett, J., Haldane, K., Jayasena, T., Loo, C., Martin, D. M., Mason, N. L., Millard, M., Nikolin, S., Solaja, I., Weiss, B., Xu, M., Xu, X.

This systematic review & meta-analysis (2024; s=10; n=304) synthesized data from contemporary studies, including both randomised and non-randomised controlled trials, to evaluate lasting effects of serotonergic psychedelics on cognition, creativity, emotional processing, and personality. Overall, no statistically significant effects were observed for most outcome measures; however, a meta-analysis of emotional recognition outcomes revealed faster reaction times in the active treatment groups for disgust and sadness.

Dhein, S., Gergs, U., Hofmann, B., Kirchhefer, U., Neumann, J.

This review (2024) outlines the effects of various hallucinogenic drugs on the human heart (contraction force & heart rate). These drugs, including bufotenin, psilocin, psilocybin, LSD, ergotamine, ergometrine, DMT, & 5-MeO-DMT, primarily stimulate serotonin receptors, particularly 5-HT2A receptors in the brain, leading to their hallucinogenic effects. However, they also impact the heart, potentially increasing cardiac contractility and heart rate, which could predispose individuals to arrhythmias.

De Filippo, R., Schmitz, D.

This hypothesis paper proposes that psychedelic agents like LSD and psilocybin induce altered states of consciousness by activating the 5-HT2A receptor system, leading to a state of synthetic surprise. This concept is based on recent understandings of serotonin's role in signaling surprise and is framed within the predictive coding framework, where surprise is seen as a mismatch between expectations and sensory input. The paper suggests that psychedelics disrupt maladaptive patterns by dynamically interacting with top-down expectations and sensory data, with implications for their clinical use, particularly emphasizing their ability to induce surprise to promote therapeutic effects.

de Wit, H., Frohlich, J, Haggarty, C. J., Lee, R., Murray, C., Tare, I.

This re-analysis (n=73) investigates the effects of low doses of LSD (13-26µg; n=21), THC (7.5-15mg), and methamphetamine (MA; 10-20mg) on neural complexity in healthy volunteers without inducing altered states of consciousness. Utilizing a within-subjects design over three laboratory visits, the study records resting state EEG data to measure Lempel-Ziv complexity and spectral power. Results demonstrate that only LSD, not THC or MA, dose-dependently increases neural complexity and reduces delta and theta power, while THC and MA respectively decrease and increase alpha power, primarily in frontal regions.

Barba, T., Carhart-Harris, R. L., Erritzoe, D., Kettner, H., Kuc, J., Nutt, D. J., Siva, J. B.

This prospective survey (n=161) examines the interactions between psychedelics and serotonergic antidepressants (SRIs), focusing on their effects on well-being and depressive symptoms. Utilizing multivariate analysis and linear mixed effect models, it compares subjective psychedelic experiences and post-use well-being between individuals on SRIs ('SRI +') and those not ('SRI −'). Findings indicate 'SRI −' participants experience more intense mystical, challenging, and emotional breakthroughs, while 'SRI +' participants have less intense experiences but similar improvements in well-being and depressive symptoms.

Bershad, A. K., de Wit, H., Hsu, D. T.

This double-blind, placebo-controlled crossover trial (n=36) investigates the effects of two doses of MDMA (52.5-105mg/70kg) compared to both placebo and methamphetamine (20 mg) on responses to personalized social feedback in healthy adults. The study concludes that the higher dose of MDMA increases positive affective responses to social feedback, suggesting a potential mechanism by which MDMA may enhance social connection.

de Wit, H., Murphy, R., Muthukumaraswamy, S.

This systematic review (s=14) compiles double-blind, placebo-controlled studies on microdosing LSD (5-20μg) under laboratory conditions. It reports that acute low doses of LSD affect blood pressure, sleep, neural connectivity, mood, social cognition, and perceptions of pain and time, with noticeable effects at 10-20 μg but not at 5μg. While no serious adverse effects were noted, repeated microdosing did not significantly change mood or cognition.

Baggot, M. J., Baker, L. E., Baumann, M. H., Johnson, C. B., Walther, D.

This in vitro and in vivo study investigates novel analogues of the designer drug 5-(2-methylaminopropyl) benzofuran (5-MAPB) as potential MDMA-like monoamine releasers. The research reveals that the S isomers of 5- and 6-(2-methylaminobutyl)benzofuran (5-MABB and 6-MABB) exhibit efficacy as releasing agents for serotonin, norepinephrine, and dopamine transporters. In contrast, the R isomers show reduced potency in inducing behavioural effects, suggesting the aminoalkyl benzofuran scaffold is a potential template for developing compounds with MDMA-like properties.

Carhart-Harris, R. L., Erritzoe, D., Nutt, D. J., Rosas, F. E., Szigeti, B., Weiss, B.

This secondary of an RCT (n=55) compared escitalopram and psilocybin (COMP360) for treating depression (MDD). Patients had higher expectancy for psilocybin, but only expectancy for escitalopram predicted therapeutic outcomes. Additionally, pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, suggesting psychedelic therapy may be less vulnerable to expectancy biases, and highly suggestible individuals may be primed for response to psilocybin treatment.

Anderson, B. T., Beaussant, Y., Bouchet, L., Nigam, K. B., Petridis, P. D., Ross, S., Sager, Z., Yrondi, A.

This systematic review (n=1400; s=36) aimed to assess the prevalence of older adults in psychedelic clinical trials and explore safety data. Only 19 participants aged 65 or older were identified, constituting less than 1.4% of all trial participants. Detailed safety data for 10 of these older adults revealed no serious adverse events, with only transient mild-to-moderate adverse events related to anxiety, gastrointestinal upset, and hypertension during psychedelic dosing sessions.

Brendstrup-Brix, K., Fisher, P. M., Fjeld, T., Grzywacz, M., Jensen, R. H., Johansen, S. S., Klausen, I. L., Knudsen, G. M., Larsen, S. M. U., Linnet, K., Madsen, M. K., Mathiesen, T., Nykjær, C. H., Overgaard-Hansen, O., Petersen, A. S., Schiønning, H., Sørensen, I. M., Stenbæk, D. S.

This open-label study (n=10) finds that three moderate doses of psilocybin (10mg/70kg) significantly reduced the frequency of chronic cluster headaches (CCH). On average, the frequency was reduced by 30%. One participant was free from CCHs for 21 weeks.

Cao, B., D'Andrea, G., Di Vincenzo, J. D., Ho, R., Kwan, A. T. H., Le, G. H., McIntyre, R. S., Meshkat, S., Rosenblat, J. D., Teopiz, K. M., Wong, S.

This systematic review (s=5) of randomised controlled trials (RCTs) compares oral psilocybin (25mg) and intranasal esketamine (56-84mg) with an oral antidepressant in adults with depression (TRD). The review showed significant depressive symptom reduction with psilocybin (Number Needed to Treat; NNT=5) and esketamine (NNT=7). Psilocybin has a Number Needed to Harm (NNH) of 5 for nausea, while esketamine induces mild side effects (NNH<10).

Aita, S. L., Borgogna, N. C., Hill, B. D., Johnson, D. A. L., Owen, T., Vaughn, J.

This systematic review & meta-analysis (2024; s=6; n=221) of randomised control trials (RCTs) on ketamine interventions for PTSD finds a small advantage for ketamine over control conditions in reducing PTSD symptoms at 24 hours post-initial infusion, but bias and heterogeneity pose concerns, indicating that blind penetration and the placebo effect might contribute to reported therapeutic effects.

Billac, G. B., Flanagan, T. W., Foster T. P., Galbato, T. E., Halberstadt, A. L., Louie, B., Lum, P. Y., Nichols, C. D., Song, G.

This in vitro study examines functional selectivity between two 5-HT2A receptor agonists, (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] and (R)-2,5-dimethoxy-4-trifluoromethylamphetamine [(R)-DOTFM], in the context of their impact on inflammation and airway hyperresponsiveness (AHR) in a murine asthma model. Despite similar in vitro activity and behavioral potency, (R)-DOTFM does not prevent inflammation or elevated AHR, in contrast to (R)-DOI, suggesting distinct anti-inflammatory mechanisms associated with certain psychedelics.

Calder, A. E., Hasler, G., Rouaud, A.

This review (2023) assesses the potential long-term impact of microdosing psychedelics on cardiac health, particularly focusing on LSD and psilocybin. Despite the increasing popularity of microdosing, concerns arise due to structural similarities between these substances and medications associated with cardiac fibrosis and valvulopathy. The review emphasizes the need for future studies to evaluate the safety of prolonged microdosing and discusses the relationship between drug-induced cardiac fibrosis and the 5-HT2B receptor.

Barrett, A. B., Bor, D., Carhart-Harris, R. L., Feilding, A., Kaelen, M., Kringelbach, M. L., Mediano, P. A. M., Muthukumaraswamy, S., Nutt, D. J., Rosas, F. E., Roseman, L., Seth, A. K., Timmermann, C.

This further analysis of data from a single-blind, placebo-controlled study (n=20) on the effects of LSD (75µg) finds that the context (eyes closed/open, silence/music/video) modulates the level of brain entropy. The study finds that eyes-closed elicited the biggest response, and that video (external stimuli) disrupts the correlation between brain entropy and subjective ratings of the experience.

Agnorelli, C., Barba, T., Benway, T., Boyce, M., Campbell, G., Erritzoe, D., Good, M., Hughes, C., James, E., Joel, Z., Jones, M., Routledge, C., Timmermann, C., Topping, H., Weiss, B.

This Phase I study (n=44) investigates the safety, tolerability, pharmacokinetics, and -dynamic profile of escalating doses of SPL026 (DMT fumarate; 9-21.5mg) in psychedelic-naïve healthy participants. The RCT concludes that SPL026 was well-tolerated, showing an acceptable safety profile, with potential correlations between plasma concentration and psychometric measures.

Bedrosian, L., Cooker, A., Doblin, R., Emerson, A., Harrison, C., Mithoefer, M. C., van der Kolk, B., Wang, J. B., Yazar-Klosinski, B., Yehuda, R.

This re-analysis of an RCT of MDMA-assisted therapy for PTSD finds that study participants (n=90) had significant improvements in the measures of self-experience (e.g. alexithymia -; the inability to identify & describe emotions experienced by oneself). The change in scores of self-experience correlates with recovery from PTSD.

Evans, J., Fisher, A., Ketzitzidou-Argyri, E., Luke, D., McAlpine, R., Michelle, K., Murphy-Beiner, A., Prideaux, E., Robinson, O., Sahely, A., Sundeman, S.

This qualitative study (n=608) investigated coping strategies employed by individuals experiencing difficulties persisting for at least one day after a psychedelic experience. Predominant individual coping strategies included meditation and prayer, along with self-educational activities like reading and journaling. Social coping methods were commonly seeking support from friends or family, and obtaining assistance from a therapist or coach, with reported benefits including feeling heard, accepted, and sharing similar experiences.

Aicher, H. D., Dornbierer, D. A., Mueller, M. J., Scheidegger, M.

This crossover RCT (n=31) investigates the effects of a novel ayahuasca-inspired formulation containing harmine and DMT in healthy male subjects. It finds that the combination of DMT and harmine, but not harmine alone, leads to a psychedelic experience with psychological insights, emotional breakthroughs, and low challenging experiences. The study reports positive persisting effects at 1- and 4-month follow-ups, with no changes in personality traits, psychological flexibility, general well-being, or increases in psychopathology.

Egan, G. F., Novelli, L., Preller, K. H., Razi, A., Stoliker, D., Vollenweider, F. X.

This follow-up fMRI analysis of an RCT of healthy subjects (n=24) finds that psilocybin (15mg/70kg) led to a pattern of decreased top-down effectivity between the default mode network (DMN), salience network (SN), and central executive network (CEN) to the amygdala.

Williams, N. R.

This observational study (n=30) evaluates ibogaine (up to 980mg/70kg) in combination with magnesium (1-2 hours before and 12 hours later) in male Special Operations Forces veterans with predominantly mild traumatic brain injury (mTBI). The study assessed changes in disability, PTSD, depression, and anxiety immediately and one month after treatment using various scales. Results show significant improvements in functioning and psychological symptoms with no serious adverse events.

Allen, J., Dames, S., Foldi, C. J., Shultz, S. R.

This review (2023) explores the potential of psychedelics as a therapeutic intervention for acquired brain injury (ABI), such as traumatic brain injury (TBI) and stroke. It highlights the challenge in managing ABI despite medical advancements and suggests psychedelics may improve neurobehavioral outcomes due to their impact on serotonin receptors, sigma-1 receptors, and neurotrophic signalling.

Kettner, H., Mithoefer, A. T., Mithoefer, M. C., Ross, S., Wagner, A. C., Weiss, B., Zeifman, R. J.

This analysis of a clinical trial (n=22) examines the role of therapeutic alliance in MDMA-assisted psychotherapy (MDMA-AP) for treating chronic PTSD. It reports that after controlling for baseline PTSD severity, a strong therapeutic alliance at the mid and late stages of treatment (sessions 4 and 9) significantly predicts lower clinician-assessed and self-reported PTSD severity post-treatment.

Almeida, R., Araújo, D. B., Arcoverde, E., Arichelle, F., Barbosa, D. C., Barros, H., Bolcont, R., Falchi-Carvalho, M., Florence-Vilela, R., Galvão-Coelho, N. L., Laborde, S., Macedo, R. K. A., Montanini, D., Palhano-Fontes, F., Pantrigo, E. J., Silva, S. R. B., Teixeira, E., Wießner, I.

This open-label Phase IIa clinical trial (n=6) examines the efficacy of vaporized DMT in treating treatment-resistant depression (TRD). Patients experienced significant reductions in two depression scores (MADRS & PHQ-9), with 83% responding to treatment by day 7 and 66.67% achieving remission. The rapid onset and sustained antidepressant effects of vaporized DMT suggest its potential as a practical and accessible option in psychedelic treatments for depression within interventional psychiatry.

Brauer, E., Dunlop, B. W., Grant, G. H., Luján-Jiménez, J. E., Maples-Keller, J. L., Mascaro, J. S., Palitsky, R., Peacock, C., Rab, F., Raison, C. L., Zarrabi, A. J.

This qualitative study (n=15) explores the roles and competencies of spiritual health practitioners in psychedelic-assisted therapy (PAT). The findings reveal seven themes, categorizing unique contributions like competency with spiritual material and awareness of power dynamics, as well as general contributions such as utilizing a therapeutic repertoire and fostering interdisciplinary collaboration. The study emphasizes the importance of delineating the roles and qualifications of spiritual health practitioners to enhance the quality and standards of care in PAT teams.

Amarneh, D., Averill, L. A., Jha, M. K., Kim, S., Lee, J., Mathew, S. J., Murphy, N., Nandra, G. S., O'Brien, B., Pannu, P., Swann, A. C., Tamman, A. J. F.

This community-based study (n=295) examined the impact of intravenous ketamine treatment on suicidality. Using growth mixture modelling, three trajectory groups were identified: one with moderate baseline scores showing gradual improvement (n=170, 57.6%), another with severe baseline scores showing no improvement (n=63, 21%), and a third with rapid improvement (n=62, 21%). Among clinical and demographic variables, only higher scores on active thoughts of death and/or plan predicted a lack of benefit from treatment for those with severe baseline CHRT-SR scores. The findings support ketamine's potential effectiveness in addressing suicidality in a proportion of patients.

Almeida, R., Araújo, D. B., Arcoverde, E., Arichelle, F., Assuncao, A., Barros, H., Bolcont, R., Costa-Macedo, J. V., Falchi, M., Galvão-Coelho, N. L., Laborde, S., Maia, L. O., Palhano-Fontes, F., Pantrigo, E. J., Silva, S. R. B., Silva-Costa, N., Tullman, S., Wießner, I.

This open-label, single-ascending, fixed-order dose-response study (n=27) investigates the safety and tolerability of inhaled DMT. The healthy volunteers received varying doses of inhaled DMT (5-60mg). Preliminary findings indicate dose-dependent increases in intensity, valence, and perceptual ratings, with no significant safety concerns, suggesting inhaled DMT as a potentially efficient and safe administration method.

Andriola, I., Barlati, S., Clericij, M., D'Andrea, G., Dell'Osso, B., Di Lorenzo, G., Di Nicola, M., Mansur, R. B., Martinotti, G., McIntyre, R. S., Pettorruso, M., Rhee, T. G., Rosenblat, J. D., Rosso, G., Sensi, S. L.

This combined analysis of two cohorts (n=311) compared intravenous ketamine (KET-IV) and intranasal esketamine (ESK-NS) in the treatment of Treatment-Resistant Depression (TRD). The study found that KET-IV (n=171) had larger effect sizes and higher response rates than ESK-NS (n=140), although both significantly reduced depressive symptoms. Despite KET-IV having more reported side effects, its discontinuation rate due to adverse events was not significantly higher than ESK-NS.

Arnon, T., Berkovich-Ohana, A., Bouso, J. C., David, J., Dor-Ziderman, Y., Kohek, M., Ona, G., Tadmor, N.

This cross-sectional research on ayahuasca-induced Personal Death (APD) experiences involves two studies. Study 1 (n=54) reveals that over half of participants in ayahuasca ceremonies report APDs, which are intense and transformative, leading to an increased sense of transcending death and certainty in consciousness continuation. Study 2 (n=306) supports these findings, showing no demographic or psychopathology associations with APDs but linking them to heightened environmental concern, improved coping abilities, and a greater sense of fulfilment in life. Overall, the studies suggest that APDs during ayahuasca ceremonies may contribute to long-term positive effects in non-clinical populations.

Borkel, L. F., Del Pino, A. S., Henríquez-Hernández, L. A., Quintana-Hernández, D. J., Rojas-Hernández, J.

This survey (n=1022) investigated the correlation between set and setting variables in psychedelic therapy with psychopathology, well-being, and personality. Findings suggest that growth motivations, natural settings, and the presence of significant others predict positive outcomes. In contrast, problematic motivations are associated with greater psychopathology and lower well-being.

Agrawal, M., Beaussant, Y., Guérin, B., Ljuslin, M., Miner, S., Nigam, K. B., Sager, Z., Sanders, J. J., Tarbi, E., Thambi, P., Tulsky, J.

This interview study (n=28) explored the acceptability of psilocybin-assisted group therapy in patients with cancer and depression (MDD) who were part of a clinical trial. Through semi-structured interviews, it found a generally positive view towards group therapy, highlighting its role in enhancing participants' safety, preparedness, connection, and belonging. The study identified key factors influencing acceptability, including the therapeutic framework's importance, the complementary nature of individual sessions, and the impact of group size and interaction structure.

Agrawal, M., Ameli, R., Bates, M., Beaussant, Y., Honstein, H., Jenkins, B., Richards, B. D., Richards, W. A., Roddy, K., Schor, N., Shnayder, S., Stevens, N., Thambi, P.

This Phase II, open-label trial (n=30) assessed psilocybin-assisted therapy (25mg) for patients with cancer and depression (MDD) with individual and group therapeutic support. The study reported no serious adverse events and suggested efficacy with a significant reduction in depression severity by week 8. Notably, 80% of participants had a sustained response, and 50% achieved full remission of depressive symptoms at week 1, maintained for eight weeks. The study highlights the safety and feasibility of psilocybin-assisted therapy in a group cohort.

Elmahy, N., Hernandez, A. V., Schiff, B., Sicignano, D. J., White, C. M.

This systematic review and meta-analysis (s=6; 2023) assessed the role of psychedelics in treating alcoholism (AUD). LSD and any psychedelic therapy showed enhanced odds of achieving abstinence or reducing alcohol consumption in randomised, double-blind, placebo-controlled trials. However, the study highlights methodological weaknesses in the literature. It suggests that while promising, definitive statements about the value of psychedelics in treating AUD are precluded, emphasizing the need for future trials with greater rigour.

Du, Z., Jiang, Y., Shen, Y., Zhou, Q., Zhu, H.

This retrospective analysis (n=5061) of FAERS data on esketamine from 2019 to 2023 reveals 117 adverse reactions. In addition to known adverse events, new signals like flashback, tachyphylaxis, and autoscopy were identified. Suicidal ideation and attempts were relatively high, emphasizing the need for vigilance, while issues related to nasal administration, such as monitoring procedure errors and discomfort, were highlighted.

Brand, M., Gründer, G., Jungaberle, H., Kartner, L., Mertens, L. J., Scharf, D. J., Spangemacher, M., Wolff, M.

This opinion piece (2023) challenges the traditional conceptualization of psychedelic-assisted psychotherapy (PAP/PAT), emphasizing that the therapeutic effects of psychedelics should not be solely attributed to the substance itself but also to the importance of psychotherapy. The authors argue against reducing the role of psychotherapy to mere psychological support for safety, advocating for a more integrated approach to understanding and studying the therapeutic potential of psychedelics in treating psychiatric disorders.

Bradley, M. K., Carhart-Harris, R. L., Dourron, H. M., Hendricks, P. S., Nichols, C. D., Simonsson, O.

This review (2023) of 5-MeO-DMT, a tryptamine with unique antidepressant potential, notes its distinct effects compared to typical psychedelics. It draws parallels between 5-MeO-DMT's effects and epileptiform activity, particularly through 5-HT1A receptor interactions, suggesting its therapeutic action may resemble electroconvulsive therapy (ECT).

Bola, M., Hobot, J., Orłowski, P., Ruban, A., Szczypiński, J.

This cross-sectional study (n=111) investigated neural markers associated with emotional reactivity in individuals with extensive naturalistic psychedelic use (15 or more lifetime experiences) compared to non-users. Experienced psychedelic users (n=56) exhibited significantly lower N200 amplitudes in response to fearful faces, suggesting reduced reactivity to emotionally negative stimuli at early processing stages.

Beller, N., Campbell, W. K., Erritzoe, D., Sleep, C., Weiss, B.

This survey (n=426) explores psychedelic-mediated personality changes, identifying 52 unique themes and 8 factors like Unitive Spiritual and Emotional Stability. It finds psychedelic users more open, extraverted, and less neurotic than non-users. The study suggests a model linking personality to psychedelic use and its impact on personality, emphasizing the need for holistic measures in psychedelic-assisted therapeutics.

Beller, N., Campbell, W. K., Dinh-Williams, L., Raugh, I. M., Strauss, G. P., Weiss, B.

This mixed-methods case series study (n=8) investigated the impact of a 3-day ayahuasca intervention on military veterans with PTSD. Results indicate that 87.5% of participants demonstrated clinically significant improvements in PTSD symptoms post-treatment, with 70% maintaining these changes at a 3-month follow-up. Veterans also reported significant improvements in momentary PTSD symptoms and daily life affect, citing deep positive emotions, decentering/acceptance, and purpose in life as perceived benefits.

Amico, E., Kloft, L., Mallaroni, P., Mason, N. L., Ramaekers, J. G., Reckweg, J., Toennes, S. W., Tolle, H. M., van Oorsouw, K.

This fMRI study (n=21) of people who regularly use ayahuasca within the Santo Daime church finds that during the experience, changes in functional connectivity (FC, how brain areas communicate) indicate on the scans more similarity between them (so less 'unique' FC). The authors use an analogy that each person still has their own hairstyle, but instead of wearing different coloured t-shirts, all are now wearing the same shirt.

Agrawal, M., Bertozzi, S. M., Kahn, J. G., Marseille, E., Mithoefer, M. C., Roddy, K., Stauffer, C., Thambi, P.

This economic analysis (2023) from two psychedelic therapy trials (MDMA-PTSD & psilocybin-MDD) with group and individual therapy aims to assess clinician time, costs, and patient access. Group therapy demonstrated cost savings of 50.9% for MDMA-PTSD and 34.7% for psilocybin-MDD, potentially reducing the need for full-time equivalent clinicians by 6,711 for MDMA-PTSD and 1,159 for psilocybin-MDD in the U.S., leading to projected savings of up to $10.3 billion and $2.0 billion, respectively, over ten years. Adopting group therapy protocols is suggested to enhance efficiency, reduce costs, and address the shortage of trained clinicians, thereby improving access to psychedelic-assisted therapies.

Aaronson, S. T., LaPratt, J., Lauterbach, M., Miller, T., Sackeim, H. A., Shoultz, A., Suppes, T., Swartz, K., van der Vaart, A.

This open-label trial (n=15) investigated the safety and efficacy of a single dose of synthetic psilocybin (25 mg) in patients with Bipolar II disorder (BDII) experiencing a current depressive episode. The study found significant improvements in depression (MADRS) scores at three weeks posttreatment, with 12 participants meeting the response criterion and 11 achieving remission. The results suggest the potential efficacy and safety of psilocybin with psychotherapy in treating BDII.

Angerer, V., Auwärter, V., Brandt, S. D., Buchwald, A., Franz, F., Gnann, A., Gnann, H., Helmecke, S., Liechti, M. E., Passie, T., Schmid, Y., Speer, J. M.

This non-blinded study (n=6) investigated the acute psychoactive, autonomic, and endocrine effects of the new psychoactive substance (NPS) 5,6-methylenedioxy-2-aminoindane (MDAI) at a dose of 3.0 mg/kg. Compared to placebo-controlled studies on MDMA, MDAI, well-tolerated, produced subjective effects similar to 125 mg of MDMA, increased blood pressure similarly, but did not increase heart rate or body temperature. MDAI also elevated cortisol and prolactin levels, remaining detectable in serum for at least 4 days and in urine for at least 6 days. Further clinical investigations are suggested to explore MDAI's potential medicinal properties.

Baltes, A., Brown, R. T., Horton, D. M., Hutson, P. R., Malicki, J., Nicholas, C. R.

This safety-feasibility trial (n=2) explored the interaction between psilocybin and buprenorphine in adults with opioid use disorder (OUD). The study found that coadministration of psilocybin and buprenorphine was safely tolerated, with no serious adverse events or significant changes in opioid craving or withdrawal measures. Feasibility challenges led to modifications in the study population and eligibility criteria, emphasizing the need for improved accessibility and overall generalizability.

de Wit, H., Lee, R., Molla, H. M., Tare, I.

This double-blind, randomised, placebo-controlled, crossover trial (n=39) finds a low dose of LSD (26μg) to produce greater positive mood, stimulant-like, and psychedelic effects in people with mild depression (BDI-II≥17) compared to non-depressed controls. Self-rated depression scores decreased more 48 hours after LSD for the mildly depressed group. Both groups showed expected physiological and subjective drug effects. This suggests low-dose LSD may have therapeutic potential for depression.

Harduf, A., Harel, E. V., Panishev, G., Salomon, R., Stern, Y.

This experimental study (n=75) investigates the impact of psychedelic and psychiatric experiences on the sense of self. It finds that patients with psychosis exhibited reduced Body Ownership and Sense of Agency, while participants with substantial psychedelic experiences reported enduring subjective changes to the sense of self, although no differences were found at the level of the bodily self when compared to control participants.

Earp, B. D., Gill, M., Hannikainen, I. R., Johnson, K., Sandbrink, J. D., Savulescu, J., Yaden, D. B.

This national survey (n=795) in the USA assesses public attitudes towards psilocybin use in licensed settings for psychiatric treatment and well-being enhancement. Participants from across the political spectrum overwhelmingly viewed the individual's decision as morally positive in both contexts, suggesting strong bipartisan support for supervised psilocybin use.

Alonzo, A., Barton, D., Baune, B. T., Berk, M., Boyce, P., Carter, G. T., Chatterton, M. L., Dong, V., Fitzgerald, P. B., Fourrier, C., Gainsford, K., Galvez-Ortiz, V., Garg, D., Glozier, N., Glue, P., Hackett, M., Hadzi-Pavlovic, D., Holtzheimer, P. E., Hood, S., Kozel, F. A., Lapidus, K., Leyden, J., Loo, C., Martin, D., McDonald, W., Mihalopoulos, C., Mills, N. T., Mitchell, P. B., Nikolin, S., Richardson, K., Riva-Posse, P., Rodgers, A., Rozakis, D., Sarma, S., Scaria, A., Somogyi, A. A., Stratton, E., Thornton, N. L. R.

This Phase III, double-blind, randomised trial (n=174) evaluated the acute efficacy and safety of a 4-week course of ketamine (35-63mg/70kg) in participants with treatment-resistant depression (TRD). The study found that ketamine was more efficacious than midazolam (1.75mg/70kg) in the flexible-dose cohort (remission rate 19.6% vs 2.0%), demonstrating that adequately dosed subcutaneous racemic ketamine is both effective and safe in treating TRD over 4 weeks.

Berghella, A. P., Garcia-Romeu, A., Hendricks, P. S., Johnson, M. W., Levine, M., Nayak, S., Rohde, J., Yaden, D. B., Yaden, M. E.

This review (2023) discusses the potential integration of classic psychedelic-assisted therapies (PAT) into current clinical practices for substance use disorders (SUDs). With promising results from initial studies, the authors suggest that classic psychedelic-assisted therapies could become legally available options for SUD patients in the future. The article outlines contemporary evidence-based treatments for SUDs and proposes that classic psychedelic-assisted therapies can be broadly compatible with existing mainstream SUD treatment paradigms, offering a new avenue for exploration in addressing these disorders.

Aicher, H. D., Boxler, M. I., Dornbierer, D. A., Kometer, M., Kosanic, D., Kraemer, T., Landolt, H-P., Marten, L., Mueller, J., Mueller, M. J., Puchkov, M., Scheidegger, M., Seifritz, E., von Rotz, R.

This open-label within-subject study (n=10) compared the oral administration of a capsule (containing DMT and harmine) with combined intranasal administration of an oromucosal harmine tablet and an intranasal DMT spray at two doses. The research aimed to improve the pharmacokinetics and tolerability profiles of ayahuasca-analogue formulations. Results indicate that the combined buccal/intranasal administration substantially attenuated common side effects and yielded significantly improved pharmacokinetic profiles. This suggests it may be an innovative approach for the safe and patient-oriented administration of DMT/harmine for treating affective disorders.

August, R. J., Averill, L. A., Barr, N., Barsuglia, J. P., Bass, L. C., Gaffrey, M. S., Jackson, L. K., Kaiyo, M., Khan, R., Ragnhildstveit, A., Seli, P.

This longitudinal case study (n=1) explores the therapeutic potential of 5-MeO-DMT in a 23-year-old female with chronic refractory PTSD. A single dose led to clinically significant improvements, including reductions in hopelessness and suicide risk, with sustained effects at 1-, 3-, 6-, and 12-month follow-ups, though not without reported risks such as acute nausea, overwhelming effects, and late-onset night terrors.

Halman, A., Kong, G., Perkins, D., Sarris, J.

This systematic review of 52 studies (n=7102) investigates drug-drug interactions between classic psychedelics (LSD, psilocybin, mescaline, DMT, 5-MeO-DMT, and ayahuasca) and various drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilizers, and recreational drugs. The findings reveal diverse interactions, ranging from attenuated to potentiated effects, with a few cases reporting no changes. Despite a lack of serious adverse events in most studies, the review emphasizes the need for a comprehensive understanding of potential interactions and explores molecular pathways underlying observed effects.

Amirouche, A., Benyamina, A., Fauvel, B., Kervadec, E., Piolino, P., Romeo, B., Strika-Bruneau, L., Verroust, V.

This retrospective online survey (n=160) investigates the impact of naturalistic psychedelic experiences on alcohol use (AUD) and related measures. The results indicate a significant reduction in the mean number of drinking days per week and AUDIT scores after the psychedelic experience. Subjects who quit or reduced drinking had a more severe AUD and lower psychological flexibility before the psychedelic session. The study suggests that positive health outcomes, including reduced alcohol use and dependency, may be associated with the intensity of the mystical experience and an increase in psychological flexibility.

Garcia, A. M., Maia, L. O., Meireles, E., Nogueira, D. A., Tófoli, L.F.

This cross-sectional survey (n=517) assessed the psychometric properties of the Spiritual Well-Being Scale (SWBS) concerning existential well-being (EWB) and religious well-being (RWB). The study found that the RWB factor exhibited superior psychometric indices for validity, group discrimination, and reliability, showing a U-shaped pattern in the association between psychedelics and spiritual well-being, where non-users and frequent users had higher RWB and EWB indices than occasional users.

Andersen, K. A. A., Grønnerød, C., Jacobsen, H. B., Kvam, T-M., Refsum, B. B., Stewart, L. H., Tunstad, P. A., Uthaug, M. V.

This cross-sectional survey (n=841) of Norwegian adults who had memorable experiences with classic psychedelic substances reveals that the primary intentions for use were recreational (46.1%) or therapeutic (42.3%). Most participants reported psilocybin as their most memorable experience, and despite the prevalence of self-perceived symptoms of mental and substance use disorders, the psychedelic experience generally led to improvements. Adverse reactions, mostly mild and short-lived, affected 4.2% for a year or more, and persisting flashbacks were reported by 2.9% of participants.

Araújo, D. B., Cruz, L., Favero, B. B., Mograbi, D. C., Tófoli, L.F.

This quantitative analysis (n=29) explores the self-reported experiences of first-time ayahuasca users, including nine individuals with treatment-resistant depression (TRD) and 20 healthy controls. Using quantitative textual analysis, five clusters were identified: alterations in consciousness, cognitive changes, somatic alterations, auditory experiences, and visual perceptual content. Individuals with depression displayed specific features, such as increased aversive bodily reactions.

Abbasi-Asl, R., Bor, D., Candia-Rivera, D., Carhart-Harris, R. L., Garfinkel, S., Gazzaley, A., Kringelbach, M. L., Luppi, A. I., Mediano, P. A. M., Muthukumaraswamy, S., Rosas, F. E., Timmermann, C.

This pre-print (2023) utilizes a novel Bayesian framework to assess autonomic markers, particularly heart rate dynamics, in tracking the effects of psychedelics, including LSD, DMT, psilocybin, and ketamine. The study, encompassing datasets from these drugs, reveals consistent increases in mean heart rate, high-frequency heart rate variability, and heart rate entropy during psychedelic experiences, with these effects demonstrating predictive power over various dimensions of the psychedelic experience. The findings suggest that cost-efficient autonomic measures, particularly heart rate entropy, can provide valuable insights into subjective and brain states during psychedelic experiences, opening new avenues for research in both basic and clinical neuroscience.

Lafrance, A., Miller, A. K., Williams, M.

This qualitative study (n=15) explores the perspectives of ayahuasca ceremony leaders, primarily from the West/Global North, on the suitability of ceremonial ayahuasca use for individuals with eating disorders (EDs). The analysis identifies categories such as screening for EDs, purging and dietary restrictions, potential risks, and complementarity with conventional ED treatment. The findings suggest the need for careful screening and extra support to ensure safe and beneficial ayahuasca ceremony experiences for individuals with EDs.

Aguilar-Valles, A., Benetatos, J., Bonniwell, E. M., Cameron, L. P., Castrén, E., Jaster, A. M., Lewis, V., McCorvy, J. D., Moliner, R., Palner, M.

This mini-review (2023) provides insights into the complex mechanisms of action of serotonergic psychedelics, such as psilocybin and LSD, emphasizing their activation of serotonin receptors, particularly 5-HT2A receptors, leading to alterations in perception, cognition, and emotions. The review explores the role of neuroplasticity in their therapeutic potential for mental health conditions and discusses interactions with other serotonin receptor subtypes and neurotrophin receptors. Additionally, it highlights the emerging interest in developing non-hallucinogenic derivatives to retain therapeutic benefits while minimizing the risk of adverse reactions and explores the potential of psychedelics in post-translational modification of proteins as part of their mechanism of action.

Bouso, J. C., Colomina, M. T., Dos Santos, R. G., Hallak, J. E., Ona, G., Reverte, I., Rossi, G. N.

This review (2023) examines ibogaine as a potential treatment for substance use disorders (SUDs). The lack of randomised, controlled studies on its safety and efficacy and the elusive mechanisms of action have been barriers to clinical use. The review suggests that ibogaine and its metabolite, noribogaine (NOR), modulate multiple targets associated with SUDs, emphasizing a complex, multi-target approach to understanding its pharmacology.

Khan, S. A., Koike, S., Peters, A. J., Rowell. S., Schreiber, M.

This retrospective analysis (n=841) of the Prehospital Tranexamic Acid Use for Traumatic Brain Injury trial evaluates the effects of ketamine in subjects with traumatic brain injury (TBI). It finds no significant difference in mortality or disability between ketamine-exposed (15.5%) and unexposed subjects, though ketamine exposure was associated with fewer instances of elevated intracranial pressure and a lower increase in TBI protein biomarkers, despite a higher likelihood of seizure activity in the ketamine group.

Jacobs, E., Murphy-Beiner, A., Nutt, D. J., Rouiller, I., Spriggs, M. J.

This perspective article (2023) discusses the ethical considerations of providing post-trial access (PTA) in psychedelic clinical trials. It highlights the unique aspects of psychedelic trials, such as the legal status of psychedelics, the researcher-participant relationship, and the extended therapeutic process, as factors supporting the case for introducing PTA. The authors also advocate for a broader focus on post-trial care beyond access and provide an overview of potential provisions for psychedelic clinical trials, emphasizing the development of infrastructure for the post-legalisation psychedelic medicine ecosystem.

Chaves, B. D. R., Fernandes-Nascimento, M. H., Negrão, A. B., Viana-Ferreira, K., Yuan-Pang, W.

This review (2023) examines the interest in ibogaine's therapeutic potential for substance use disorders over three decades (1993-2022). The study identifies a linear growth of publications in the first and third decades, with academic research centers in the United States and Canada being the most productive. Major keywords shifted from cocaine, tobacco, morphine, and alcohol in the first two decades to opioids and psychedelics in the third decade, indicating evolving research trends.

Amico, E., Farah, J. C., Mallaroni, P., Mason, N. L., Ramaekers, J. G., Tolle, H. M.

This re-analysis (n=48) of a double-blind study on the effects of psilocybin (12mg, n=21) finds that function connectomes (FCs) become more idiosyncratic, especially in the default-mode network (DMN). Looking specifically at the DMN, the researchers find reduced within-DMN activity and more connectivity with attentional systems.

Ashton, M., Bartha, A., Carhart-Harris, R. L., Eckernäs, E., Erritzoe, D., Gascon-Perai, K., Gomes, L., Jagger, S., Luan, L., Nutt, D. J., Rosas, F. E., Timmermann, C., Uthaug, M. V.

This single-blind, placebo-controlled crossover study (n=11) investigated a novel administration method for DMT involving a bolus injection followed by a constant-rate infusion to extend the experience over 30 minutes. Results demonstrate that the method was safe and maintained stable subjective effects, although the plateauing of psychological effects despite rising plasma concentrations suggests the development of acute tolerance.

Anger, J., Dubinskaya, A., Eilber, K., Komisaruk, B. R., Suyama, J., Wexler, A.

This systematic review (2023, s=14) examines the effects of MDMA on the male and female sexual response cycles. Among women, MDMA showed increased sexual desire in 4 out of 6 studies, while in men, it exhibited varied effects on desire, arousal, and erectile function. Both genders experienced delayed orgasm but increased intensity and pleasure upon achieving it. Overall, while MDMA generally increased sexual desire and intensified orgasms, it presented conflicting evidence regarding sexual arousal and potentially impaired erectile and ejaculatory function in men.

Evans, J., Ketzitzidou-Argyri, E., McAlpine, R., Murphy-Beiner, A., Robinson, O., Suseelan, S.

This mixed-method study (n=608) explored prolonged adverse effects following psychedelic use, revealing extended challenges persisting for weeks, months, or even years in some cases. One-third of participants experienced problems for over a year, with a sixth enduring these difficulties for over three years. Factors such as knowledge of dosage, drug type, and lower reported difficulty during the experience influenced the duration and range of these challenges. In contrast, guided settings during drug intake appeared to narrow the spectrum of problems.

Chambers, R., Goldberg, S. B., Hendricks, P. S., Osika, W., Simonsson, C., Simonsson, O.

This epidemiological study (n=2822, n=613 with lifetime psychedelic use) explored associations between naturalistic psychedelic use and psychiatric risks in a US adult sample. Findings showed lifetime psychedelic use linked with more unusual visual experiences throughout life but no direct connection to recent psychotic symptoms. An interaction between lifetime psychedelic use and family history of psychotic or bipolar disorders revealed higher recent psychotic symptoms in individuals with both factors, and lower symptoms without such family history.

Ahmed, O. J., Brooks, I., Donoho, E., Ekins, T. G., Jedrasiak-Cape, I., Kailasa, S., Mashour, G. A., Rech, J., Rybicki-Kler, C.

This pre-print mice study explores the impact of classical psychedelic drugs on pyramidal cells in the prefrontal cortex. Contrary to previous beliefs, the study reveals that various classes of psychedelics dose-dependently decrease intrinsic excitability of pyramidal neurons. The mechanism behind this effect involves enhancing ubiquitously expressed potassium M-current channels, independent of serotonin 2A receptor activation. Machine-learning-based data assimilation models suggest that M-current activation, in conjunction with known mechanisms, significantly reduces intrinsic excitability and shortens working memory timespan. The findings propose that psychedelic drugs modulate brain-wide ion channels, potentially triggering homeostatic adjustments and contributing to widespread therapeutic benefits.

Amen, S., Ben-Zion, Z., Danböck, S. K., Duek, O., Harpaz-Rotem, I., Kelmendi, B., Korem, N., Levy, I., Wilhelm, F. H.

This randomised controlled pilot study (n=26) investigated the effect of ketamine on resting-state functional connectivity (RSFC) between amygdala and medial prefrontal cortex (mPFC) subregions. Contrary to expectations, ketamine did not increase RSFC between these areas but instead led to a transient decrease in vmPFC-amygdala RSFC in individuals with PTSD. These results challenge prior correlations and suggest a need for further exploration and a more nuanced understanding of the neurobiological basis of dissociative phenomena in PTSD.

Bartolucci, G., Brugnami, A., Camardese, G., Caso, R., Di Nicola, M., Fischetti, A., Grisoni, F., Marcelli, I., Mazza, M., Pepe, M., Pesaresi, F., Sani, G.

This open-label prospective study (n=25) evaluated esketamine nasal spray (ESK-NS) treatment for treatment-resistant depression (TRD). Over three months, patients reported early and sustained improvements in depression, anhedonia, and suicidality, while clinicians detected improvements that varied at different time points.

Goldberg, S. B., Hendricks, P. S., Honk, L., Osika, W., Simonsson, O., Stenfords, C. U. D.

This longitudinal observational study (n=9,732) aimed to investigate potential associations between self-reported psychedelic use and meditation practice in the US and UK adult populations. The study found that psychedelic use during a 2-month period was associated with increased engagement in mindfulness meditation practice, and the subjective experience of insight during psychedelic use was linked to greater involvement in mindfulness and loving-kindness or compassion meditation. Additionally, the research indicated that baseline engagement in loving-kindness or compassion meditation was associated with reduced severity of challenging experiences during psychedelic use.

Bertrand, C., Deisseroth, K., Gray, N. J., Hack, L. M., Heifets, B. D., Hilton, R., Knutson, B., Rodriguez, C. I., Roessell, P. J. V., Suppes, T., Williams, L. M., Yesavage, J. A., Zhang, X.

This placebo-controlled study (n=13) investigated the effects of ketamine (3.5-35mg/70kg) on altered states of consciousness (ASCs) and their neural mechanisms. It examined the impact of different doses of ketamine on emotional task-evoked brain activity and various components of dissociation and ASCs. The study found that ketamine-induced ASCs had differential effects on brain activity, with higher depersonalization relieving negative brain states, while dissociative amnesia exacerbated insula activity. These results may provide insights into how specific dissociative states predict the response to ketamine in individuals with depression.

Cianfichi, L. J., Flohr, J. R., Hack, L. M., Heifets, B. D., Lii, T. R., Nyongesa, C. A., Okada, R. L., Schatzberg, A. F., Smith, A. E.

This triple-masked, randomised, placebo-controlled trial (n=40) of adults with major depressive disorder (MDD) found no short-term effect on depression severity (measured by MADRS) after a single dose of intravenous ketamine (35mg/70kg) compared to placebo (saline) during anaesthesia for routine surgery.

Haijen, E. C. H. M., Hurks, P. P. M., Kuypers, K. P. C.

This observational study (n=233) investigates the impact of four weeks of microdosing (MD) on mindfulness and personality traits in adults with ADHD. Findings indicate increased mindfulness and decreased neuroticism post-MD, with no significant changes in other personality traits. The use of conventional ADHD medication or the presence of comorbidities didn't affect the outcomes, suggesting MD may alter stable traits independently of these factors.

Chen-Li, D., Fancy, F., Haikazian, S., Husain, M. I., Johnson, D., Levinta, A., Mansur, R. B., McIntyre, R. S., Rosenblat, J. D.

This systematic review analyzed the effects of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. The review included 13 studies with a total of 686 participants, and the meta-analysis of 9 studies (596 participants) found a significant and large effect in favor of psilocybin (SMD = -0.78; p<0.001) for reducing depressive symptoms. The review suggests preliminary evidence supporting the antidepressant efficacy of psilocybin-assisted psychotherapy but calls for further studies to assess safety, efficacy, and treatment optimization.

Carhart-Harris, R. L., Chiacchiaretta, P., Ferretti, A., Martinotti, G., Nutt, D. J., Onofrj, M., Penna, S. D., Pizzi, S. D., Roseman, L., Sensi, S. L., Sestieri, C., Slater, C. B. T., Tullo, M. G.

This re-analysis study (n=20) investigated the impact of acute LSD (75μg) administration on thalamocortical connectivity in healthy volunteers. The study utilized structural and resting-state fMRI to examine the thalamus at the nucleus-specific level. LSD intake was found to increase functional connectivity between the thalamus's ventral complex, pulvinar, and non-specific nuclei, particularly with sensory cortices such as somatosensory and auditory networks, as well as parts of the associative cortex dense in serotonin type 2A receptors. The study also reported decreased connectivity between the striatum and thalamus.

Mimura, M., Nakajima, S., Nomoto-Takahashi, K., Ohtani, Y., Tani, H., Uchida, H., Yatomi, T., Yonezawa, K.

This study analyzed data from an RCT (n=31) with treatment-resistant depression (TRD) who received therapeutic doses of intravenous ketamine (35 to 70mg/70kg). The research found that a later onset of depression was positively correlated with a better treatment response to ketamine after three days of administration, suggesting that earlier disease onset may be associated with impaired glutamatergic signal transmission and reduced neuroplasticity, which diminishes the response to ketamine. Other demographic and clinical factors, including age, sex, baseline depression score, and dissociative score, didn't significantly correlate with treatment response.

Duerler, P., Gubser, L. P., Lewis, C. R., Michels, L., Moujaes, F. F., Preller, K. H., Rieser, N. M., Vollenweider, F. X.

This study (n=70) aimed to explore the effects of three oral doses of psilocybin (11-15mg) versus placebo on cerebral blood flow (CBF). Changes in blood flow in the brain caused by psilocybin were different for each person and depended on their initial brain conditions and how they felt during the psychedelic experience. This suggests that people have varying responses in their brains to psilocybin.

Enriquez-Geppert, S,, Krc, J., Lietz, M. P., O'Higgins, F.

This experimental study (n=37) explored the integration of psilocybin-assisted neurofeedback in individuals with psychiatric disorders and executive function deficits. The participants received three microdose sessions followed by three psilocybin-assisted neurofeedback sessions. While there were no immediate improvements in experimental tasks assessing executive functions, significant self-reported improvements in daily life executive functions were observed, including working memory, shifting, monitoring, and inhibition, with high effect sizes.

Bahceci, D., Chatterton, M. L., Davey, C. G., Glozier, N., Hopwood, M., Loo, C., Rodgers, A.

This analysis highlights the challenges in repurposing established medicines, using ketamine as a case study for treating severe depression. Generic ketamine's efficacy was known for over two decades, but commercial disinterest and lack of support delayed its approval. Instead, a costly patented formulation, Spravato®, gained widespread acceptance despite emerging evidence of generic ketamine's similar effectiveness. Systemic reforms are essential to prevent a repeat scenario with new psychedelic-assisted psychotherapy treatments, including commercial incentives, public funding, and reduced regulatory barriers.

Greń, J., Kiraly, C., Lasocik, M., Tylš, F.

This article (2023) presents proposed comprehensive guidelines for psychedelic integration, developed through an international, bottom-up project that involved literature reviews and roundtable discussions. These guidelines aim to fill the gap in mental health specialist training, providing theoretical and practical insights into psychedelic integration. They cover topics such as the effects of psychedelics, the definition of psychedelic integration, theoretical considerations, a model for integration practice, current integration models, and specific interventions from various psychotherapeutic approaches.

Allison, S., Baracaldo, L., Card, K. G., Closson, K., Grewal, A., Kruger, D. J., Martin, G., Walsh, Z.

This survey (n=1,249) assessed interest in and acceptability of psilocybin use among individuals who have experienced adverse childhood experiences. The study found high interest in psilocybin, and its use was associated with reduced psychological distress among those with more severe childhood adversity, indicating its potential therapeutic benefits for this group.

Basbaum, A., Corder, G., Dworkin, R. H., Edwards, R. R., Eickhoff, C. R., Larsen, I. B., Linguiti, S., McKinstry-Wu, A., Pines, A., Roalf, D. R., Satterthwaite, T. D., Scott, J. C., Sharma, V., Strain, E. C., Sydnor, V. J., Vogel, J. W., Wellman, N.

This systematic review (s=51) examines fMRI studies on the acute effects of psychedelics like psilocybin, LSD, and ketamine on the human brain. The review highlights significant methodological inconsistencies across studies, including 54% not meeting contemporary Type I error correction or motion artefact control standards. Despite these limitations, convergent findings indicate that psilocybin and LSD affect the connectivity architecture of the sensorimotor-association cortical axis, while ketamine increases activation in the dorsomedial prefrontal cortex.

Buchborn, T., Kartner, L., Kettner, H., Meinhardt, M. W.

This review (2023) focuses on the role of the ego in psychedelic-assisted psychotherapy (PAT), particularly through a psychodynamic lens. It argues that psychedelics induce regressed states of the ego, allowing for emotional integration of early life events that have shaped a person's character and defence mechanisms. The paper posits that for lasting change, PAT must target the characterological core of the ego's habitual patterns, and it suggests that this psycholytic approach is compatible with other forms of PAT like third-wave cognitive behavioural approaches (CBT/ACT).

Carter, B., Cleare, A. J., Ko, K., Rucker, J.

This re-analysis of a Phase I randomised controlled trial (n=89) investigated predictors of mystical and challenging experiences in healthy volunteers receiving psilocybin. It finds that dosage was the strongest predictor of intensity for both experience types, while older age was associated with fewer challenging experiences and neuroticism correlated with challenging experiences only at the higher dose.

Bitter, I., Buyze, J., Cebulla, K., Frey, R., Fu, D. J., Ito, T., Kambarov, Y., Llorca, P-M., Messer, T., Mulhern-Haughey, S., Oliveira-Maia, A. J., Reif, A.

This open-label Phase IIIb trial (n=676) compared the efficacy of esketamine nasal spray and extended-release quetiapine, combined with an SSRI or SNRI, in patients with treatment-resistant depression (TRD). The study found that a significantly higher percentage of patients in the esketamine group achieved remission at week 8 (27.1% vs 17.6%) and had no relapse through week 32 after remission at week 8 (21.7% vs 14.1%). Adverse events were consistent with the established safety profiles of the trial treatments.

Kloft, L., Mallaroni, P., Mason, N. L., Ramaekers, J. G., Reckweg, J., van Oorsouw, K.

This neuroimaging study (n=24 ayahuasca users from Santo Daime & case-matched controls) examined the relationship between cortical gene expression markers and brain morphometric changes following repeated ayahuasca use. It found that repeated ayahuasca usage was associated with spatially distributed cortical structural differentiation in sensorimotor areas and de-differentiation in transmodal areas, correlated with dysregulation of 5-HT2A gene expression and genes encoding target receptors. The study suggests preliminary evidence that molecular mechanisms of psychedelic action may influence large-scale brain organization, potentially accounting for behavioural differences in experienced psychedelic users.

Bojarski, A. J., Brandt, T. G., Casado-Sainz, A., Cumming, P., Czurylo, J., Herth, M. M., Jensen, A. A., Jessen, N. S., Kiilerich, K. F., Kjaerby, C., Lorenz, J., Overgaard, A., Palner, M., Satała, G., Scharff, M. B., Shalgunov, V., Speth, N., Xiong. M.

This rat study established and validated a regimen for psilocybin microdosing, administering repeated low doses of psilocybin at a level below the psychedelic threshold. The rats tolerated the regimen well without showing signs of anhedonia, anxiety, or altered locomotor activity. Additionally, the treatment imparted resilience against stress, reduced self-grooming behaviours associated with compulsiveness, and increased 5-HT7 receptor expression and synaptic density in the paraventricular nucleus of the thalamus.

Azouz, Z., Côté, S. M., Galéra, C., Galesne, C., Jean, F. A. M., Macalli, M., Montagni, I., Navarro, M. C., Schwartz, A. N., Tzourio, C.

This observational survey study of university students (n=13,837) explored the association between ADHD symptoms and lifetime psychoactive substance use. It finds a significant correlation between high levels of ADHD symptoms and the use of various substances, including ketamine and psilocybin mushrooms.

Acar, K., Cabrera, A. E., Horntvedt, O., Ingvar, M., Lebedev, A. V., Osika, W., Petrovic, P., Simonsson, O.

This cross-sectional study (n=392) examined the relationship between psychedelic use and beliefs in alternative facts in a sample that included 233 individuals with a history of psychedelic use. The study found a moderate positive association between psychedelic use and beliefs in alternative facts, particularly the belief that facts are politically influenced. However, there were no significant associations between psychedelic use and favoring intuition over evidence when confirming facts. Additionally, alcohol was negatively associated with beliefs in alternative facts. Overall, the study suggests that psychedelic use is linked to non-conformist thinking styles, possibly due to the psychological effects of the drugs or shared traits related to unconventional beliefs and substance use.

González-Maeso, J., Jaster, A. M.

This review (2023) discusses the investigation of psychedelics for their therapeutic potential in neuropsychiatric and substance use disorders. Clinical trials have shown promise in alleviating symptoms of depression, anxiety, and reducing nicotine and alcohol use. The underlying molecular mechanisms for these therapeutic effects are not yet fully understood, with ongoing preclinical studies exploring the role of serotonin 5-HT2A receptors and other pathways.

Erritzoe, D., Harding, R., Nutt, D. J., Rabiner, E. A., Wall, M. B., Zafar, R.

This review (2023) discusses the emerging field of psychedelic therapy for psychiatric disorders, emphasizing the potential of classic serotonergic psychedelics like psilocybin and LSD and substances like ketamine, MDMA, and ibogaine. It highlights the role of advanced neuroscientific research methods, particularly neuroimaging using Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI), in advancing the understanding of drug and therapy effects on the brain. The article identifies key knowledge gaps, including the relationship between acute and longer-term effects, the precise characterization of effects at the 5-HT2A receptor, and the impact of these compounds on neuroplasticity, and proposes a roadmap for future research to address these questions through multimodal PET/MRI studies.

Bremler, R., Carhart-Harris, R. L., Erritzoe, D., Katati, N., Shergill, P.

This survey (n=32) and interview (n=15) study of those who had negative psychological responses to psychedelics (>72 hours) identified potential causal factors, such as unsafe or complex environments during or surrounding the experience, prior psychological vulnerabilities, high or unknown drug quantities, and young age. However, due to the small sample size and selective recruitment approach, the study can't be used to infer the prevalence of adverse outcomes from psychedelic use.

Bowyer, K., Chen, C., Chiu, Y-T., Deutch, A. Y., DiBerto, J. F., English, J., Herman, M. A., Huang, K. L., Hua, K., Kocak, D. D., Liu, B., Llorach, P., Mott, S. E., Niehaus, J., Roth, B. L., Scherrer, G., Schmitz, G. P., Sciaky, N., Walsh, J. J., Wang, W., Wetsel, W. C., Wu, Z.

This pre-print mice study utilized a suite of engineered mouse models, including Htr2a-EGFP-CT-IRES-CreERT2 mice, humanized Htr2a mice, and constitutive Htr2A-Cre mice, to investigate the role of the 5-hydroxytryptamine 2A receptor (HTR2A) and HTR2A-expressing neurons in the actions of psychedelic drugs such as LSD and psilocybin. These mice exhibited behavioural responses consistent with the known effects of psychedelics, and electrophysiology studies demonstrated an HTR2A-mediated increase in the firing of genetically identified pyramidal neurons.

Fried, E. I., van Elk, M.

This critical review (2023) examines the challenges currently facing psychedelic research, which has seen a surge of interest in recent years for its potential in treating mental disorders. The paper identifies ten pressing challenges, categorized into easy, moderate, and hard problems, that threaten the validity of key findings in this field. These challenges encompass issues related to internal validity, external validity, construct validity, and statistical conclusion validity, which collectively limit the ability to draw definitive conclusions about the safety and efficacy of psychedelic therapy. The paper also offers a roadmap for addressing these challenges.

Apud, I., Carrera, I., Hernandez, G., Lozano, F., Retta, J. I., Rodriguez, L., Scuro, J.

This study (n=44) analyzed Uruguayan ayahuasca users in neo-shamanic and Santo Daime groups through chemical tests, ethnography, and psychometrics. Santo Daime participants scored lower in certain personality traits, possibly due to the neo-shamanic group's treatment or Santo Daime's religious framework. The neo-shamanic group had higher scores in Somesthesia and Perception, likely due to their high-arousal rituals.

de Wit, H., Lee, R., Lyubomirsky, S., Molla, H. M.

This randomised, controlled trial (n=18 MDMA, n=19 methamphetamine) investigates the effects of MDMA (100 mg) and methamphetamine (MA; 20 mg) on feelings of connectedness during a semi-structured casual conversation with an unfamiliar partner. The study finds that MDMA and MA increased feelings of connection and elevated oxytocin levels compared to placebo. However, a correlation between increased oxytocin levels and feelings of closeness was observed only in the MDMA group, highlighting MDMA's unique empathogenic effects.

Averill, L. A., Davis, A. K., Sepeda, N. D., Xin, Y.

This open-label study (n=86) examined the effectiveness of psychedelic-assisted therapy (PAT) among trauma-exposed Special Operations Forces Veterans (SOFV) in Mexico. Results indicated significant improvements in self-reported PTSD symptoms, depression, anxiety, insomnia severity, post-concussive symptoms, satisfaction with life, psychological flexibility, and cognitive functioning from baseline to one-month follow-up. The combination of ibogaine and 5-MeO-DMT assisted therapy showed potential for providing rapid and lasting improvements in mental health functioning, with effects observed up to six months after treatment.

Advenier-Iakovlev, E., Danon, M., De Maricourt, P., Estrade, I., Gaillard, R., Gorwood, P., Leroy, S., Mancusi, R. L., Mekaoui, L., Perrain, R., Petit, A-C., Poupon, D., Sylvestre, V., Vinckier, F.

This longitudinal study (n=50, confirmatory sample n=55) investigated the use of esketamine in patients with treatment-resistant depression (TRD) and aimed to define distinct response trajectories. The study identified two classes, one representing response and the other non-response, influenced by factors like concomitant benzodiazepine medication, number of depressive episodes, or polarity. After two esketamine administrations, the depression score (MADRS) predicted the 90-day response trajectory with 80% accuracy, suggesting clinicians could use MADRS scores to decide whether to continue treatment in TRD patients.

Arakelian, M., Barnett, B. S., Beebe, D., Ontko, J., Pope Jr, H. G., Riegal, C., Siu, W. O., Weleff, J.

This survey (n=131) conducted among American psychiatrists, aimed to assess their opinions about psychedelics & PAT in 2023, comparing the results with a similar study conducted in 2016. The findings revealed a significant positive shift in attitudes among American psychiatrists since 2016, with a majority expressing moderate to strong belief in the therapeutic potential of psychedelics for treating psychiatric conditions (81%) and substance use disorders (61%).

Anticevic, A., Corlett, P. R., Kaye, A. P., Krystal, J. H., Preller, K. H.

This commentary (2023) explores the neurobiological mechanisms underlying the experience of meaningfulness induced by psychedelics, focusing on 5-HT2A receptor activation. It proposes multiple hypotheses: 1) 5-HT2A activation increases the salience of environmental stimuli, 2) psychedelics may reactivate salient autobiographical memories, and 3) psychedelics may create novel neural representations that generate prediction errors.

Barrett, F. S., Brasher, T., Garcia-Romeu, A., Griffiths, R. R., Jackson, H., Johnson, M. W., Jolly, D. R. P., Lowe, M. X., Mathai, D. S., Nayak, S., Sepeda, N. D., So, S., Strickland, J. C., Yaffe, A., Zaki, H.

This prospective longitudinal study (n=2,833) examined naturalistic psilocybin use among adults outside of clinical research settings. Participants were primarily college-educated White men in the United States who used dried psilocybin mushrooms for self-exploration. The study found that after psilocybin use, there were persisting reductions in anxiety, depression, and alcohol misuse, increased cognitive flexibility, emotion regulation, spiritual well-being, and extraversion, as well as reduced neuroticism and burnout. However, a minority of participants (11% at 2-4 weeks and 7% at 2-3 months) reported persisting negative effects. Overall, this is the largest prospective survey of naturalistic psilocybin use to date and supports the potential for psilocybin to produce lasting improvements in mental health symptoms and general well-being.

Abbate, V., Faber, S., Greenway, K. T., La Torre, J. T., Mahammadli, M., Williams, M. T.

This expert consultation study (n=12) investigated the exclusion of individuals with personal or familial histories of psychopathological experiences from most psychedelic clinical trials and treatment programs. Experts in psychiatry, clinical psychology, medicine, and psychedelics were interviewed, and the findings revealed that exclusion criteria may be justified in studies with minimal psychological support. They agreed that psychedelic-assisted psychotherapy, as well as therapy with MDMA and ketamine, might be beneficial for some individuals within this group.

Canal, C. E., Saraf, T. S., Tyagi, R.

This mouse study investigated the effects of N,N-dipropyltryptamine (DPT), a psychedelic tryptamine, on audiogenic seizures in a mouse model of fragile X syndrome (genetic cause of autism). DPT was found to prevent seizures at a 10 mg/kg dose completely but not at lower doses (3 or 5.6 mg/kg). Despite being a serotonin receptor agonist, the antiepileptic effects of DPT were not mediated through specific serotonin receptor subtypes (5-HT2A, 5-HT1B, or 5-HT1A), nor through sigma1 receptors.

Bentancourt, I., Bramen, J., Heinzerling, K. G., Kelly, D. F., Linton, M., Rich, R., Schwartzberg, L., Sergi, K., Siddarth, P., Youssef, B.

This open-label pilot study (n=20) investigated the use of Visual Healing, a nature-themed video intervention, to enhance set and setting in psychedelic-assisted therapy with psilocybin for alcohol use disorder (AUD). Participants were randomised to either use Visual Healing or standard procedures during two psilocybin dosing sessions. The study found that Visual Healing was feasible, safe, and well-tolerated, with participants viewing the videos without adverse events. It also noted a significant decrease in alcohol use in both groups and found that Visual Healing did not interfere with the psychedelic experience or treatment outcomes related to alcohol use. The study suggests that Visual Healing may reduce cardiovascular risks in psychedelic therapy and calls for further research to replicate these findings and explore set and setting interventions with other psychedelic medications and indications.

Allard, P., Dames, S., Gloeckler, S. G., Greenway, K. T., Johnny, C., Manson, E., Peekeekoot, G., Ryding, E., Taylor, W.

This pilot program (n=8, +2 Elders) explored the effectiveness and safety of group-based therapy augmented by three sessions of ketamine at a psychedelic dose for Indigenous participants in partnership with Roots to Thrive and the Snuneymuxw First Nation. Thematic analysis of qualitative interviews and feedback revealed participant motivations, perceived barriers, program benefits, and psychedelic experiences. Participants emphasized the importance of Indigenous team members, incorporating traditional healing approaches, and fostering authentic relationships between participants and facilitators, highlighting both challenges and significant program benefits. The article underscores the need for reconciliation efforts within and beyond psychedelic therapies.

Balliett, B., Bogenschutz, M. P., de Boer, A., Doblin, R., Gelfand, Y., Hamilton, S., Harrison, C., Kleiman, S., Mitchell, J., Mithoefer, A. T., Nicholas, C. R., Ot’alora G, M., Paleos, C., Parker-Guilbert, K., Quevedo, S., Shannon, S., Tzarfaty, K., van der Kolk, B., Yazar-Klosinski, B.

This multi-site, randomised, double-blind, Phase IIIb trial (n=104) evaluated the efficacy and safety of MDMA-assisted therapy (MDMA-AT) for individuals with moderate to severe PTSD. The study found significant reductions in PTSD severity (CAPS-5 score) and functional impairment (SDS score) for the MDMA-AT group compared to placebo with therapy. Seven participants experienced severe treatment-emergent adverse events, but no deaths or serious adverse events were reported. The treatment was found to be generally well tolerated in a diverse population.

Hu, Z., Lan, X-F., Li, W., Liu, H., Mai, S., Ning, Y-P., Wang, C-Y., Ye, Y., Zhang, F., Zhou, Y-L.

This randomised-controlled trial (n=51) assessed the short-term effects of three subanesthetic esketamine infusions (17.5mg/70kg) in adolescents aged 13-18 with major depressive disorder (MDD) and suicidal ideation. The study found a significant improvement in processing speed and working memory in the esketamine group from baseline to days 6 and 12, with no harm to cognition observed. However, there was no significant association between baseline cognition and the antidepressant or antisuicidal effects of esketamine.

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). The data suggests that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated.

Alcázar-Córcoles, M. A., Bouso, J. C., Dos Santos, R. G., Hallak, J. E., Ona, G., Révész, D., Rocha, J. M., Rossi, G. N.

This longitudinal transcultural study (n=2971) conducted during the peak of the COVID-19 pandemic in April 2020 collected data through an online survey from English-, Spanish-, and Portuguese-speaking participants. The study found that users of hallucinogenic drugs, particularly regular users, had higher psychological well-being and lower psychopathology scores both at baseline and during follow-ups. Regular hallucinogen users also showed higher scores for post-traumatic growth, especially among subjects with more psychological distress. The study noted variations between cultural contexts, with more English-speaking participants reporting regular use of hallucinogenic drugs.

Hooker, J. M., Olson, D. E., Wallace, R. M.

This viewpoint (2023) explores the concept of neuroplasticity, which is increasingly used in mainstream discourse to describe how the brain responds to various stimuli. Neuroplasticity is a complex concept encompassing molecular, cellular, and circuit-level changes and their impact on human behaviour. The article aims to comprehensively understand neuroplasticity by engaging experts from various scientific disciplines. It emphasizes its relevance in healthy and diseased conditions, highlighting its importance in chemical neuroscience.

Armstrong, S. B., Averill, L. A., Davis, A. K., Sepeda, N. D., Xin, Y.

This prospective study (n=86) examined the effects of ibogaine and 5-MeO-DMT treatment on U.S. Special Operations Forces Veterans with trauma exposure. Younger age and higher baseline levels of depression and anxiety were correlated with significant improvements in mental and psychosocial outcomes from baseline to 1-month follow-up. Greater intensity of changes in consciousness was linked to improved long-term mental health and psychosocial outcomes up to 6 months post-treatment.

Ashton, M., Carhart-Harris, R. L., Eckernäs, E., Koomen, J., Röshammar, D., Timmermann, C.

This study designed an infusion protocol for DMT using pharmacokinetic/pharmacodynamic modelling. Comparing a continuous variable model to two bounded integer models, optimal doses for desired psychedelic intensity were identified. However, achieving consistent target intensity was challenging across models, indicating individual dose adjustments might be needed. Differences between models were especially notable at the scale's boundaries.

de la Torre, R., Hutten, N. P. W., Kuypers, K. P. C., Mallaroni, P., Mason, N. L., Ramaekers, J. G., Reckweg, J., Szabo, A., Tse, D. H. Y.

This double-blind placebo-controlled paper (n=60) explores the effects psilocybin (12mg/70kg) has on a range of inflammatory markers associated with stress-related psychiatric disorders. Blood samples, MRI and questionnaires were used to assess different aspects of the immune response. Psilocybin immediately reduced levels of the inflammation-inducing TNF-α while other markers were unchanged. After seven days, TNF-α returned to baseline while levels of IL-6 and CRP were reduced in the psilocybin group, which were associated with more persisting positive mood and social effects.

Lindauer, R., van Dam, L., van Vugt, A. S., Zijlmans, J.

This focus group study (n=19) investigated the perspectives of adolescents, parents, and clinicians on MDMA-assisted psychotherapy for adolescents with PTSD. Initial attitudes towards MDMA were mainly unfavourable, but after an explanation of the therapy, all but one participant supported its potential use, emphasizing the importance of research.

Griffiths, R. R., Raison, C. L., Ross, S., Sanacora, G., Woolley, J. D.

This Phase II trial (n=104) evaluated the effects of a single dose of psilocybin (25mg) vs niacin (100mg) placebo in adults with moderate or severe depression (MDD). Psilocybin treatment significantly reduced depression scores (MADRS & Sheehan Disability Scale) compared to niacin up to day 43. While there were no serious treatment-emergent adverse events, psilocybin was associated with a higher rate of overall and severe adverse events.

Barnett, B. S., Claytor, B., Kovacevich, A., Weleff, J.

This case report (n=3) documents the first academic instances of olfactory improvement after psychedelic use. The study also discusses potential mechanisms, such as serotonergic effects, neuroplasticity, and anti-inflammatory effects, suggesting further research into psychedelics for olfactory dysfunction.

Garcia, A. M., Loizaga-Velder, A., Marcus, O., Mendive, F., Rush, B., Spitalier, A.

This naturalistic study (n=52) assessed the one-year post-treatment outcomes of the Takiwasi Centre's ayahuasca-assisted program for addiction rehabilitation in Peru. Using various validated instruments, results showed significant group improvements from baseline to one-year follow-up in alcohol and drug use severity, depression, anxiety, and some quality of life dimensions. While there was individual variation in outcomes and treatment duration, most participants deemed all program aspects, especially the spiritual and therapeutic significance of the ayahuasca experience, as very important.

Garcia-Romeu, A., Griffiths, R. R., Hilbert, S. N., Mathai, D. S., Sepeda, N. D., Strickland, J. C.

This double-blind experimental study (n=20) compares the effects of high-dose dextromethorphan (DXM; 400mg/70kg) to psilocybin (10, 20, 30mg/70kg) under conditions typical of therapeutic psychedelic trials. DXM and psilocybin showed increases over placebo in ratings of experiences predictive of psychological benefit at 1 week. However, psilocybin's effects were dose-dependent and more favourable, while DXM had poorer physical tolerability.

Anderson, K., Mason, N. L., Neubert, J. J.

This qualitative study (n=12, six couples) investigates the impact of shared psychedelic experiences on intimacy within romantic relationships. Couples aged 19-29, who had used psychedelics together, were interviewed simultaneously about their shared experiences. Analysis revealed three primary themes: navigating anxiety, reshaping practices, and encountering bliss. The findings suggest that while couples' psychedelic experiences align with traditional criteria for interactional intimacy, they also introduce a unique form of psychedelic intimacy.

Jones, G. M., Nock, M. K.

This observational study (n=734k) from the National Survey on Drug Use and Health (2002-2020) explored the relationship between lifetime psilocybin use and crime arrests, considering racial and ethnic differences. Overall, psilocybin use was associated with lowered odds of crime arrests. However, race and ethnicity moderated this association for three out of four crime outcomes. Psilocybin reduced the odds of at least one crime arrest outcome for all racial and ethnic groups except Black and Hispanic participants.

Carhart-Harris, R. L., Erritzoe, D., Kettner, H., Mallard, A., Pagni, B. A., Roberts, D. E., Ross, S., Zeifman, R. J.

This prospective survey (n=698) investigated the effects of co-using MDMA (n=27) with psilocybin/LSD on challenging and positive experiences. Co-use of psilocybin/LSD with a low dose of MDMA was linked to significantly reduced challenging experiences (like grief and fear) and enhanced feelings of self-compassion, love, and gratitude. However, there were no differences in mystical-type experiences or compassion.

Abrams, S. K., Aziz, A. S., Cherup, N. P., Lewis, E. C., McMillan, D. W., Nielson, J. L., Rabinovitch, B. S., Zafar, R.

This descriptive review (2023) focuses on the reactions of persons with spinal cord injury (SCI) to classical serotonergic psychedelics like psilocybin and LSD. Anecdotal reports from online forums describe neuromuscular and autonomic hypersensitivity, including intense muscle spasms, sweating, and tremors, but with no worsening of baseline neurological deficits. The study proposes this reaction as a peripherally dominant serotonin syndrome-like clinical picture and emphasizes the need for awareness and harm reduction as psychedelic-assisted therapy (PAT) becomes more mainstream.

Aaronson, S. T., Alti, M., Carhart-Harris, R. L., Clarke, P., Dougherty, R. F., Dunlop, B. W., Goodwin, G. M., Hellerstein, D. J., Kuc, J., Ryslik, G. A., Schlosser, D., Young, A. H., Zisook, S.

This article of a language model (NLP, BART) finds that the audio from psychological support sessions (in the COMP360 trial for treatment-resistant depression, n=90 at 12 weeks) can predict clinical outcomes with high (85%) accuracy. The implications of this research signal that audio recordings can be used to predict who will respond to treatment and possibly aid in helping identify who would need more support.

Kuypers, K. P. C., Kvamme, T. L., Sarmanlu, M., Vizeli, P.

This review (2023) explores the potential mechanisms behind the efficacy of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD). The article examines recent preclinical and clinical evidence, focusing on MDMA's mnemonic (memory) effects, its impact on fear extinction and reconsolidation, and its relevance for PTSD treatment.

Bonnelle, V., Cavarra, M., Feilding, A., Kryskow, P., Kuypers, K. P. C., Mason, N. L., Ramaekers, J. G., Smith, W. J.

This survey study (n=170) aimed to understand the effectiveness of classical psychedelics in treating chronic pain conditions compared to conventional treatments. The analysis focused on five specific conditions: fibromyalgia, arthritis, migraine, tension-type headache, and sciatica. Results showed that, except for sciatica, participants reported better pain relief using psychedelics than with conventional medication. Specifically, full psychedelic doses outperformed conventional treatments, while microdoses provided significantly better relief for migraines and comparable relief for the other three conditions.

Benedek, D. M., Green, W. M., James, F. L. J., Johnson, L. R., Raut, S. B., Ursano, R. J.

This pre-print review and meta-analysis (2023) of randomised controlled trials (RCTs) assessed the effectiveness of MDMA-assisted psychotherapy (MDMA-AP/AT) for treating Post-Traumatic Stress Disorder (PTSD) and its impact on quality of life and physiological effects. The analysis found that MDMA-AP significantly improved dissociation, depression, and functional impairment in PTSD patients compared to controls, but not sleep quality.

Earleywine, M., Gordis, E. B., Kamilar-Britt, P.

This theory-building article (2023) emphasizes the importance of the therapeutic alliance, a cooperative connection between clients and providers, in psychedelic-assisted therapy (PAT). Past studies have indicated that the alliance contributes to therapy outcomes regardless of the therapy's theoretical orientation, session count, or improvement rates. The article suggests that focusing on the therapeutic alliance could enhance the understanding and effectiveness of PAT. It advocates for including alliance measures in clinical trials and highlights the benefits of enhancing the alliance through clinician behaviours that prioritize client autonomy, listening skills, and practical concerns.

Duthaler, U., Erne, L., Holze, F., Liechti, M. E.

This pharmacokinetic study (n=28) investigated the effects of oral LSD doses of 85 and 170 μg on healthy participants over 24 hours. The results showed mean maximal LSD concentrations of 1.8 ng/ml and 3.4 ng/ml for the respective doses, reaching peak concentrations after approximately 1.7 hours. Elimination half-lives were between 3.7 and 4.0 hours. Only 1% of LSD was found unchanged in urine within 24 hours, while 16% was eliminated as 2-oxo-3-hydroxy-LSD. Subjective effects lasted between 9.3 and 11 hours, with intensity peaking at 77% and 87% for the two doses.

Bonnelle, V., Buot, A., Burguière, E., Dauré, C., Dos Santos, A., Flores, J., Ljuslin, M., Mallet, L., Morgiève, M., N'Diaye, K., Oganesyan, A., Pallares, C., Smith, P., Verroust, V., Wyplosz, B.

This retrospective online survey (n=174) explores the impact of psychoactive drugs on OCD symptoms. Classic psychedelics were the only substances reported effective at reducing OCD symptoms, with symptom reduction associated with the intensity of acute effects and dose. The persistence of the therapeutic effect ranged from weeks to months, and the magnitude and duration of the medicinal impact influenced subsequent intakes.

Deng, Q., Hu, Y., Li, A., Liu, J., Wang, G., Wang, H., Xiao, C., Zhou, J., Zhu, X.

This pilot randomised clinical trial (n=30) assessed the efficacy of a single subanesthetic dose of esketamine (14mg/70kg) in enhancing the effect of oral antidepressants for patients with fluctuating responses to treatment in major depressive disorder (MDD). Participants were adults with MDD experiencing fluctuating symptoms despite prior symptom relief and stabilization. The study found that response rates at 2 weeks were significantly higher in the esketamine group (66.7%) compared to the midazolam control group (6.7%), with a more substantial reduction in depression severity (MADRS score) in the esketamine group.

Holstein, A., Klumpers, L. E., Knowles, R., Mantuani, D., Tagen, M., Van Heerden, L.

This review (2023) covers in vitro, animal, and clinical studies to assess the potential risk of valvular heart disease (VHD) from microdosing psychedelic substances, focusing on LSD, psilocybin, mescaline, DMT, and MDMA due to their interaction with the serotonin 5-HT2B receptor. Findings show that all these compounds, except mescaline (due to low potency), were partial agonists at the 5-HT2B receptor. While safety margins from typical microdoses were greater than known valvulopathogens, there remains a potential risk. No studies directly evaluated VHD risk for the four psychedelics, but some evidence suggests chronic ingestion of full doses of MDMA might be linked to VHD.

Al Jurdi, R. K., Borentain, S., Brown, B., Cabrera, P., Castro, M., Fu, D. J., Petrillo, M. P.z, Sun, L., Turkoz, I., Wilkinson, S. T., Zaki, N.

This subgroup analysis of SUSTAIN-3 (n=96) studies patients with treatment-resistant depression (TRD) who received a second induction and maintenance treatment with esketamine nasal spray (ESK) plus oral antidepressant (AD) after a relapse in SUSTAIN-1.

Barnett, B. S., Cole, S. P., Herrmann, Z., Jain, R., Jain, S., Levin, A. W., Penn, A., Raison, C. L., Rajanna, B., Slabaugh, S.

This cross-sectional online survey (n=228) examined the effects of psychedelic use on healthcare providers who treat psychiatric disorders with medications. The study found that psychedelic use was associated with improvements in depression, anxiety, well-being, and resilience, and a decrease in reported suicidality. A factor analysis indicated that a combination of mystical, interpersonal, and personal experiences predicted these improvements. The preferred psychedelic agent did not influence outcomes, and frequency of use showed varied effect sizes. While 13.2% (n=30) reported at least one harm from psychedelic use, the results suggest potential benefits for healthcare providers, consistent with findings from other studies on the general population.

Pereira, L.

This systematic review and dose-response meta-analysis (n=489) aimed to determine the optimal dosage of psilocybin for depression treatment. Seven studies were included, with four focusing on primary depression (n=366) and three on secondary depression (n=123). Specific 95% effective daily doses (ED95) were identified for each group, revealing different dose-response associations and side effects.

Barron, J., Boehnke, K. F., Cox, K., Fields, C. W., Glynos, N., Herberholz, M., Kolbman, N., Kruger, D. J., Weston, C.

This online cross-sectional survey (n=1221) aimed to assess the relationship between psychedelic use and clinical support. It found that 22% of participants disclosed psychedelic use to their primary care provider (PCP) and 58% to their psychiatric care provider (PsyCP). Despite 81% desiring therapist support during psychedelic experiences, only 15% received such support.

Schindler, E. A. D.

This review (2023) highlights the potential therapeutic use of psychedelic drugs in treating episodic migraine. The only clinical trial conducted to date found that a single low dose of psilocybin reduced weekly migraine days and pain intensity for two weeks in episodic subjects, with additional findings suggesting potential benefits in cluster headaches.

Bahji, A., Loo, C., Nikolin, S., Rodgers, A., Schwaab, A., Vazquez, G. H., Zarate, C. A.

This systematic review and meta-analysis (n=3299) investigated the efficacy of ketamine for depression by analysing 49 randomised controlled trials (RCTs). The study found that racemic ketamine had numerically greater effects on depression severity, response, and remission rates compared to esketamine. Higher doses were more effective than low doses, with differences evident in initial effects, ongoing treatment, and lasting effects post-final dose.

Dinkelacker, J., Pop, I.

This observational naturalistic study (n=17) repeatedly assessed participants during their psychedelic microdosing regimen using the CNSVS neurocognitive battery in a naturalistic setting. Results indicate that neither the day of microdosing nor the day after showed significant links to enhanced or diminished performance across various cognitive functions. The study concludes that microdosing psychedelics might influence psychological pathways rather than neurocognitive ones, leading to a subjective feeling of performance enhancement.

Anderson, E. I., Bock, H. A., Bonniwell, E. M., Calkins, M. M., Cao, A. B., Cuccurazzu, B., de Klein, R., Fannana, T., Gamrat, J., Halberstadt, A. L., Heim, A. J., Hennesssey, J. J., Klein, A. K., Lanham, J. K., McCorvy, J. D., Morris, H., Sherwood, A. M., Wallach, J. V., Zauhar, R.

This mice study investigates the role of 5-HT2A receptor activation in mediating the effects of serotonergic psychedelics. It finds that 5-HT2A-Gq efficacy, not 5-HT2A-β-arrestin2, predicts psychedelic-like potential in male mice, using the head-twitch response (HTR) as a measure. The research also reveals that β-arrestin-biased 5-HT2A receptor agonists have an anti-psychotic-like behavioural profile and can induce receptor downregulation.

Avram, M., Borgwardt, S., Holze, F., Korda, A., Ley, L., Liechti, M. E., Müller, F., Preller, K. H., Razi, A., Rogg, H., Vizeli, P.

This re-analysis of a double-blind, placebo-controlled, crossover study (n=25) investigated the effects of LSD, MDMA and dextroamphetamine on brain measures (thalamocortical and corticothalamic interactions in resting-state fMRI data). Compared to placebo, all three substances increased the effective-connectivity from the thalamus to specific unimodal cortices while reducing their influence on the thalamus, revealing increased bottom-up and decreased top-down information flow; LSD uniquely increased effective-connectivity to both unimodal and transmodal cortices.

Corazza, O., Lando, E., Mancini, M., Melelli, F., Metastasio, A., Mignogna, S., Paci, R., Stanghellini, G.

This phenomenological analysis (n=1) examines the influence of LSD on the creative insights of Federico Fellini, a renowned film director. The study explores how LSD use under controlled therapeutic guidance enhanced his creativity across four domains: time, space, body and others, and perception of the self. The resulting impacts included irregular time flow, brilliant and detached colours, independent sounds, deformed human bodies, and the collapsing boundaries between dream and reality, leading to his films' distinctive Felliniesque style.

Boehnke, K. F., Glynos, N., Kolbman, N., Kruger, D. J., Lucas, P.

This survey (n=2384) of Canadian adults reporting past use of psychedelics assesses health outcomes and integration of psychedelic use with health care providers (HCP). It finds that about 80% never discussed psychedelic use with their HCP, 34% used psychedelics to self-treat a health condition, and 45% were aware of substance testing services, and 42% had used them. The study concludes that naturalistic psychedelic use in Canada often includes therapeutic goals but is poorly connected to conventional healthcare, with substance testing being uncommon, and highlights the need for relevant training and education for HCPs, along with more visible options for substance testing.

Carhart-Harris, R. L., Erritzoe, D., Nutt, D. J., Szigeti, B.

This computational analysis (2023) employs computational modelling to illustrate how weak blinding and positive treatment expectancy can cause an uneven distribution of expectancy effects, termed 'activated expectancy bias' (AEB). The study introduces the Correct Guess Rate Curve (CGRC), a tool to estimate the results of a perfectly blinded trial using data from an imperfect one, and re-analyzed the ‘self-blinding psychedelic microdose trial’ dataset (n=191) to demonstrate that placebo-microdose differences may be susceptible to AEB, thereby suggesting microdosing can be viewed as an active placebo.

Caron-Lapointe, G., Joshi, K., Lefebvre, D., Pilon, D., Teeple, A., Zhdanava, M.

This retrospective analysis (n=535) describes the access and real-world use patterns of esketamine nasal spray among adults with treatment-resistant depression (TRD). Of the pharmacy claims for esketamine, 34.6% were approved, 46.3% were rejected, and 19.1% were abandoned. The approval rate increased to 85.2% by the second treatment session. Among 273 patients who initiated esketamine (mean age 49.3 years; 66.3% female), the mean number of sessions was 11.8 over a mean of 11.8 months, with 47.6% completing at least 8 sessions, and 93.8% of those completing induction continuing treatment.

Heifets, B. D., Olson, D. E.

This review (2023) highlights the promising rapid and sustained therapeutic effects of psychedelics and entactogens based on recent clinical and preclinical evidence. To better comprehend their impact on mental health, the review emphasizes the importance of bridging the gap between human and rodent studies and shifting the focus to circuit modulation rather than individual molecular targets.

Babakanian, A., Finn, D. M., Gruen, T., Kaye, W. H., Peck, S. K., Shao, S., Trim, J., Yang, K.

This open-label feasibility study (n=10) examines the effects of a single dose of psilocybin (25mg; COMP360) on adult female participants diagnosed with Anorexia Nervosa (AN) or pAN (partial remission). Results show that the treatment was safe, tolerable, and acceptable, with no significant changes in ECG, vital signs, or suicidality. However, two participants developed asymptomatic hypoglycemia (low blood sugar), which resolved within 24 hours. No significant changes in BMI were found.

Carhart-Harris, R. L., Davis, A. K., Erritzoe, D., Goldberg, S. B., Griffiths, R. R., Nutt, D. J., Simonsson, O.

This meta-analysis (n=102, s=3) assesses the risk of symptom worsening in psilocybin trials for depression. It reports that clinically significant symptom worsening occurred in approximately 10% of participants in the psilocybin and escitalopram conditions, and in 63.6% of participants in the waitlist condition. Psilocybin showed a lower likelihood of symptom worsening compared to waitlist, and no difference when compared to escitalopram.

Leão, R. N., Lima da Cruz, R. V., Moulin, T. C.

This pre-print review (2023, s=68) of pre-clinical (mice) studies examines the impact of psychedelic compounds on adult neurogenesis, the process of new neuron formation in the adult brain. The researchers categorize psychedelics into five main groups: CB1 agonists, NMDA antagonists, harmala alkaloids, tryptamines, and entactogens, and explore their outcomes on neurogenesis. The study concludes by asserting that psychedelics could potentially influence the generation of new neurons and other brain-related processes.

Belser, A. B., Brennan, C., Kelman, A.

This pre-print review (s=33, 2023) examines reporting practices of psychosocial interventions in clinical trials involving psychedelic treatment. The findings reveal that many reports on psychedelic trials did not disclose basic details about the interventions; 33% didn't mention the number of sessions, 45% didn't indicate the duration of sessions, 42% didn't state provider credentials, 52% didn't mention if a therapy manual was used, 67% didn't reference a manual available to readers, and 82% didn't report the assessment of treatment fidelity.

Bedi, G., Muthukumaraswamy, S., Noorani, T. N.

This anthropological commentary (2023) discusses the interplay of social elements and psychedelic-assisted therapy (PAT) clinical trials, introducing the term 'chemosociality'. The authors argue that 'dark loops', unrecorded social phenomena impacting trial experiences, tend to distort the traditional logic of causal inference, not currently accounted for in trial data interpretation.

Castelhano, J. M., Castelo-Branco, M., Gonzalo, G., Soares, C.

This meta-analysis (s=88, n=2122) investigates the overlap between the Default Mode Network (DMN) and the Theory of Mind (ToM) networks, and their modulation by psychedelics. It reveals that the cingulate cortex plays a crucial role in the overlap between these networks, and psychedelics affect their neural relationship, potentially explaining their impact on self-perception and social cognition.

Rieser, N. M.

This comparative neuroimaging study (n=107) compares the neural correlates of two pharmacological methods, psilocybin (n=23) and LSD (n=25), and two non-pharmacological methods, hypnosis (n=30) and meditation (n=29), in inducing altered states of consciousness (ASC). The results reveal distinct connectivity patterns associated with pharmacological and non-pharmacological interventions, predictability at an individual level, and unique behavioural-neural relationships between psilocybin and LSD, all contributing to a broader understanding of the mechanisms of ASC and their potential therapeutic applications in psychiatric disorders.

Frecska, E., Szabo, A., Winkelman, M. J.

This literature review (2023) examines the potential of natural and synthetic psychedelics in treating Alzheimer's Disease (AD) and related dementias. It highlights the plastogenic effects of serotonergic psychedelics and their ability to promote neuronal survival, glutamate-driven neuroplasticity, and reduce Aβ-induced neurotoxicity, illustrating the potential for these substances to address multiple facets of AD pathology.

Croal, M., Feifel, D., Goodwin, G. M., Kelly, J. R., Malievskaia, E., Marwood, L., Mistry, S., O’Keane, V., Peck, S. K., Simmons, H., Sisa, C., Stansfield, S., Tsai, J., Williams, S.

This open-label Phase II trial (n=19) investigates the safety, tolerability, and efficacy of synthetic psilocybin (COMP360) as an adjunct to selective serotonin reuptake inhibitors (SSRIs) in adults with treatment-resistant depression (TRD). The study found no serious treatment-emergent adverse events or increased suicidal ideation. It reported a significant decrease in depression (MADRS) and Clinical Global Impression-Severity (CGI-S) scores at week 3, with response and remission observed in 42.1% of participants.

Canuso, C. M., Fu, D. J., Ionescu, D. F., Jamieson, C., Lane, R., Molero, P., Qui, X., Rozjabek, H.

This pooled analysis of two Phase III studies (n=451, ASPIRE) investigates the effect of esketamine nasal spray plus standard of care on patient-reported outcomes in patients with major depressive disorder (MDD) having active suicidal ideation (SI) with intent. It found that esketamine, compared to placebo, led to significant improvements in Beck Hopelessness Scale (BHS) and Quality of Life in Depression Scale (QLDS) scores, along with perceptions of effectiveness and global satisfaction in the Treatment Satisfaction Questionnaire for Medication (TSQM-9), supporting its positive impact on health-related quality of life in this patient population.

Fonzo, G. A., Goodwin, G. M., Malievskaia, E., Nemeroff, C. B.

This commentary (2023) critically re-evaluates the role of psychedelics in psychotherapy, focusing on psilocybin's use and challenging its current understanding in mental health treatment. Concluding that psychedelic-assisted psychotherapy is a misnomer, it proposes psilocybin treatment as a more accurate term, foreseeing a future where psychedelics could precede various psychotherapies, antidepressants, or neurostimulation for specific conditions.

Lawrence, D. W., Timmermann, C.

This survey study (n=227) examined respondents' sense of familiarity after inhaling DMT. The researchers also developed the Sense of Familiarity Questionnaire (SOF-Q) which categorised the sense of familiarity into five themes, with further analysis identifying two classes of participants (entity encounters familiarity, feeling & emotion or knowledge gained familiarity).

Godes, M., Lucas, J., Vermetten, E.

This qualitative study (n=7) utilized Interpretative Phenomenological Analysis (IPA) to investigate the experiences of patients with severe PTSD participating in a Phase-II clinical trial assessing MDMA-assisted psychotherapy.

Armand, S., Fisher, P. M., Knudsen, G. M., Madsen, M. K., McCulloch, D. E-W., Olsen, A. S., Ozenne, B., Stenbæk, D. S.

This brain imaging study (n=28) evaluated the acute effects of psilocybin on 12 previously reported brain entropy metrics in healthy participants. It found a positive association for Shannon entropy of path-length and instantaneous correlation distributions, while no significant effects were observed for seven of the 12 metrics, and concluded that the acute effects of psychedelics on brain entropy are nuanced and that 'brain entropy' is not a singular construct.

Bonnieux, J. N., Garcia-Barrera, M. A., Garcia-Romeu, A., Premji, Z., VanderZwaag, B.

This review (s=42 studies) offers an overview of the effects of psilocybin on cognition and creativity. It was found that shortly after the intake of psilocybin, cognition and creativity are impaired, especially with higher doses, but these effects diminish over time and some positive effects may emerge.

Chao, Z., Fu, L., Hu, Z., Lan, X-F., Li, W., Liu, H., Ning, Y-P., Wang, C., Ye, Y., Zhang, F., Zhou, Y.

This placebo-controlled trial (n=54) investigates the efficacy and safety of esketamine (iv, 17.5mg, 3x) in adolescents suffering from depression (MDD) and suicidal ideation (SI). It shows significant reductions in Columbia Suicide Severity Rating Scale (C-SSRS) Ideation and Intensity scores and Montgomery-Åsberg Depression Rating Scale (MADRS) scores in the esketamine group compared to the midazolam (placebo) group at day six, with maintained antisuicidal and antidepressant responses at four weeks post-treatment.

Kangaslampi, S., Zijlmans, J.

This article (2023) advocates for MDMA-assisted psychotherapy (MDMA-AT) in treating adolescent PTSD, highlighting potential benefits such as reduced avoidance and enhanced therapeutic alliance. It proposes adaptations including stronger motivation reinforcement, additional emotion management techniques, and family involvement, and calls for clinical trials to assess safety and effectiveness.

Hartogsohn, I., Pronovost-Morgan, C., Ramaekers, J. G.

This review/hypothesis article (2023) proposes a new framework inspired by the field of psychedelic science, specifically focusing on the concept of “set and setting” to understand better and utilize the placebo effect in clinical settings. The authors argue that randomised controlled trials (RCTs), while helpful in evaluating the efficacy of drugs, can overlook the significance of contextual and personal factors that interact with and shape drug effects, and suggest an integrative approach that acknowledges the synergy between drug and non-drug factors for improved patient care.

Guss, J., Krause, R., Reed, S., Skinta, M. D., Sloshower, J. A., Wallace, R. M., Williams, M. T.

This double-blind, placebo-controlled, within-subject study (n=19) involved individuals with major depressive disorder (MDD). It investigated the effects of a single dose of psilocybin on electroencephalographic (EEG) correlates of neuroplasticity and depression symptoms. The results showed that EEG theta power doubled in amplitude two weeks after psilocybin administration. This increase was correlated with improvements in depression symptoms, suggesting that psilocybin may produce sustained changes in brain neuroplasticity and have antidepressant effects. Note that the improvement in depression scores was not significant vs placebo.

Benyamina, A., Fauvel, B., Piolino, P., Romeo, B., Strika-Bruneau, L., Verroust, V.

This retrospective online survey (n=173) examined the impact of a psychedelic experience on tobacco use among smokers. The results showed a significant decrease in the mean number of cigarettes smoked daily and tobacco dependency following a psychedelic experience. Participants who reduced or quit smoking had more intense mystical experiences during the psychedelic session and initially lower psychological flexibility. The study found that an increase in psychological flexibility after the psychedelic experience and personal motives for undergoing the session were significant positive predictors of smoking reduction or cessation.

Earleywine, M., Low, F.

This survey (n=363) investigated the effects of psychedelic use on grief symptoms among individuals who had experienced a bereavement event. The results indicated significant improvements in grief symptoms following a psychedelic experience, with a large effect size (Cohen's d = 0.83). Emotional breakthroughs during the psychedelic experience were positively associated with improved grief symptoms, while challenging experiences had the opposite effect.

Mason, N. L., Paci, R., Ramaekers, J. G., Reckweg, J., Terwey, T. H., Theunissen, E. L., van Leeuwen, C.

This two-part clinical trial (n=16) investigated the safety and potential antidepressant effects of vaporized 5-MeO-DMT (GH001) in patients with treatment-resistant depression (TRD). Phase I (n=8) tested two single doses (12mg and 18mg) for safety, while Phase II (n=8) evaluated an individualized dosing regimen with up to three increasing doses (6mg, 12mg, 18mg) in a single day for efficacy. The results showed GH001 was well-tolerated and had potent and rapid antidepressant effects, with 87.5% of patients in the Phase 2 group achieving remission by day seven.

Brunovský, M., Dudysová, D., Horacek, J., Janků, K., Kopřivová, J., Kuchar, M., Nikolič, M., Páleníček, T., Tylš, F., Viktorin, V., Zach, P.

This re-analysis of an RCT (n=20) investigated the effects of psilocybin on memory consolidation in healthy volunteers. The study specifically examined the impact of psilocybin on memory consolidation of material learned just after the psilocybin session and on overnight memory consolidation. The results showed that psilocybin did not improve memory consolidation, but importantly, it also did not negatively affect memory consolidation.

Bertozi, G., Bouso, J. C., Crevelin, E. J., Crippa, J. A., De Oliveira Silveira, G., Dos Santos, R. G., Hallak, J. E., Ona, G., Osório, F. L., Queiroz, M. E. C., Rocha, J. M., Rossi, G. N., Yonamine, M.

This parallel-arm, randomised controlled trial (n=17) examined the effects of cannabidiol (CBD) on the recognition of emotions in facial expressions (REFE) and empathy following the consumption of ayahuasca in healthy volunteers over 18 months. The participants received either a placebo or 600 mg of CBD, followed by oral ayahuasca (70ml/70kg) 90 minutes later. Results showed significant reductions in both groups' reaction times and anxiety, sedation, cognitive deterioration, and discomfort, but no differences were observed.

Barrett, F. S., Berghella, A. P., Doss, M. K., Sayali, C., Tiwari, P., Yaden, D. B.

This review/opinion article (2023) suggests that the reversal of and resilience against learned helplessness could be a key therapeutic mechanism of classic psychedelics in treating mood and substance use disorders. The authors argue for the utility of the learned helplessness model in psychedelic research due to its robustness across species, well-described neurobiology, and substantial overlap with neural circuits involved in psychedelic actions.

Muthukumaraswamy, S.

This commentary (2023) suggests that causal mediation analysis using objective biomarkers could help establish causal pathways between treatment and outcome, providing greater confidence in the efficacy of psychedelic therapies before they are approved as regular medicines. This cautious approach is recommended to avoid potential drawbacks such as expanding indications based on low-quality evidence and unstable efficacy over time.

de Deus, J. L., Dölen, G., Faltin, S., Goff, L. A., Lama, C., Nardou, R., Padovan-Hernandez, Y., Sawyer, E., Song, Y. J., Stein-O'Brien, G. L., Wilkinson, M., Wright, N.

This mice study shows that psychedelics (including ketamine & MDMA) open a social reward learning critical period. The duration of the drugs' effects in humans is proportional to the time it takes for the critical period to reopen. Additionally, the restoration of oxytocin-mediated long-term depression in the nucleus accumbens is associated with the reinstatement of social reward learning in adulthood. The study also found that reorganising the extracellular matrix is a common mechanism underlying the critical period reopening caused by psychedelic drugs.

Bouso, J. C., Chenhall, R., Cowlye-Court, T., Opaleye, E. S., Perkins, D., Sarris, J., Schubert, V., Tófoli, L.F.

This survey (n=1630) collected responses from ayahuasca users to explore the qualitative aspects of post-ayahuasca integration The participants described integration experiences in three main ways: overall appraisal (easy, challenging, or long-term/ongoing), beneficial tools facilitating integration (connecting with a like-minded community, yoga, meditation, journaling), and integration challenges (feeling disconnected or reconciling new understandings with old life). The findings suggest that integration can be challenging and time-consuming, but addressing these challenges may facilitate positive growth. The study also challenges the dominance of individual psychotherapy as a primary integration tool in Western psychedelic therapy and proposes an expanded definition of psychedelic integration that includes communal and somatic elements.

Agnorelli, C., Barba, T., Erritzoe, D., Harding, R., Nutt, D. J., Roseman, L., Siegel, M., Suseelan, S., Wall, M., Zafar, R.

This review (2023) charts the resurgence of interest in psychedelic therapy for treating addiction, beginning with historical studies from the mid-late 1900s, then examining real-world evidence from naturalistic, observational, and survey-based studies, and contemporary clinical trials ranging from first-in-human to Phase II. It also explores translational human neuropsychopharmacology techniques like fMRI and PET to understand the therapeutic mechanisms of psychedelics.

Beck, A., Byrne, K., Durns, T., Garland, E. L., Hendrick, J., Lewis, B. R., Thielking, P.

This open-label study (n=12) investigates the potential of psilocybin-assisted group therapy (PAT) in cancer patients suffering from depression. Participants underwent preparatory sessions, a high-dose (25mg) psilocybin group session, and integration sessions over three weeks, with clinical outcomes measured at baseline, two weeks, and 26 weeks post-intervention. Results show significant decreases in depression symptoms and no serious adverse events, suggesting safety, feasibility, and possible efficacy of the therapy.

Garcia-Romeu, A., Griffiths, R. R., Jackson, H., Nayak, S., Yaden, D. B.

This prospective longitudinal survey (n=657) finds that people who use psychedelics recreationally increase in prescribing 'mind perception' to living and non-living targets (e.g. plants and animals). However, unlike previous studies, they didn't find changes in metaphysical beliefs along the Atheist-Believer scale.

Adamska, I., Finc, K.

This analysis of earlier LSD (75μg) data investigates the effect of music on brain state dynamics using fMRI. The results indicate that the interaction of music and psychedelics led to changes in the time-varying brain activity of the task-positive state, with music potentially having a long-term influence on the resting state, particularly on states involving task-positive networks. The study concludes that music, as a crucial component of setting, may influence the resting state during a psychedelic experience.

Campbell, W. K., Erritzoe, D., Weiss, B., Wingert, A.

This study (n=339, including 33 veterans) assessing the safety and efficacy of ceremonial ayahuasca use in relation to the reexperiencing of adverse life events found that reexperiencing adverse life events under ayahuasca was common, with women being more likely to reexperience sexual assault, veterans reexperiencing combat-related trauma, and individuals with a history of PTSD having a higher likelihood of reexperiencing. Additionally, reexperiencing was associated with cognitive reappraisal, psychological flexibility, and discomfort during ceremonies, but also with greater reductions in trait neuroticism post-ceremony. The implications of these findings for using psychedelics in treating mood and stress disorders were discussed.

Antoine, D., Griffiths, R. R., Gukasayan, N., Nayak, S., Yaden, D. B.

This two-part online retrospective survey (n=2,153) analysed the interaction between psilocybin-containing mushrooms and common antidepressants. Participants who took psilocybin while on antidepressants (n=611) often experienced weaker effects than expected, particularly with SSRIs and SNRIs. Additionally, the survey showed that even after discontinuing SSRIs or SNRIs, the weakening effects on psilocybin might persist for up to 3 months (n=1,542). The study indicates that serotonergic antidepressants may reduce the effects of psilocybin.

Adams, A. M., Bloesch, E. K., Davis, A. K., Davoli, C. C., Domoff, S. E., Scherr, K., Woolley, J. D.

This prospective survey (n=54) study found that participants of an ayahuasca retreat significantly increased in nature-relatedness and -appreciation (and gratitude) one week and one month later. Ratings of the trip on mystical experience and awe correlated weakly with these changes.

Keyes, K. M., Patrick, M. E.

This longitudinal cohort study (n=11,304) analysed hallucinogen use among young adults aged 19-30 in the US from 2018 to 2021. The study found that LSD use remained relatively stable, but the use of non-LSD hallucinogens (e.g., psilocybin) increased from 3.4% in 2018 to 6.6% in 2021. Males were more likely to use non-LSD hallucinogens, as were individuals who were white or from higher socioeconomic backgrounds. The study suggests that the prevalence of past-year non-LSD hallucinogen use doubled among young adults in the US during the studied period.

Antenucci, L., Biojone, C., Brunello, C. A., Cannarozzo, C., Casarotto, S., Castrén, E., Diniz, C. R. A. F., Elsilä, L. V., Enkavi, G., Fred, S. M., Girych, M., Goncharuk, S. A., Haapaniemi, H., Kankuri, E., Kaurinkoski, K., Korpi, E. R., Kot, E. F., Koveleva, V., Kuutti, M., Meshi, E., Mineev, K. S., Moliner, R., Nagaeve, E., Öhman, T., Permi, P., Rog, T., Rubiolo, A., Saarma, M., Sakson, S., Seiffert, N., Varjosalo, M., Vattulainen, I., Vilar, M.

This mice study investigated the antidepressant and neuroplastic effects of psychedelics, specifically lysergic acid diethylamide (LSD) and psilocin. The trial centres around their high-affinity binding to TrkB, a BDNF receptor implicated in antidepressant mechanisms. These substances bind to TrkB with affinities 1,000-fold higher than other antidepressants (SSRIs), and their effects on neurotrophic signalling, plasticity, and antidepressant-like behaviour in mice depend on this TrkB binding and promotion of endogenous BDNF signalling. Interestingly, these effects are independent of serotonin (5-HT) 2A receptor activation, suggesting that TrkB is a primary target for antidepressants.

Agin-Liebes, G. I., Bogenschutz, M. P., Haas, A., Kim, K., Nielson, E. M., Owens, L. T., Rogers, U., Zingman, M.

This qualitative study (n=13) aimed to investigate the psychological mechanisms of change in psilocybin-assisted psychotherapy (PAT) for alcoholism (AUD). Participants reported that psilocybin treatment helped them process emotions related to past events, promoting self-compassion, self-awareness, and feelings of interconnectedness, which laid the foundation for better regulation of negative emotions and improved quality of relationships. The study suggests that integrating self-compassion training with psychedelic therapy may enhance psychological outcomes in treating AUD.

Amen, S., Duek, O., Gordon, C., Harpaz-Rotem, I., Kelmendi, B., Korem, N., Krystal, J. H., Levy, I., Li, Y., Milne, M.

This pilot RCT study (n=27) investigated the potential of a single ketamine infusion (35mg/70kg), followed by brief exposure therapy, to enhance the extinction of trauma memories in individuals diagnosed with PTSD. Participants were randomly assigned to receive either ketamine or midazolam after retrieval of the traumatic memory, and underwent trauma-focused psychotherapy 24 hours later for four days. While PTSD symptoms improved equally in both groups, post-treatment ketamine recipients showed lower amygdala and hippocampus reactivation to trauma memories than midazolam recipients, suggesting that ketamine may enhance the post-retrieval extinction of trauma memories.

Fisher, H., Harding, R., Knight, C., McCrone, P., Neill, J. C., Nutt, D. J., Schlag, A. K.

This study assesses the cost-effectiveness of psilocybin-assisted psychotherapy (PAP/PAT) versus conventional medication, cognitive behavioural therapy (CBT), and the combination of the two for difficult-to-treat depression (in the UK). The decision model simulates patient outcomes (response, remission, and relapse) and analyses costs and quality-adjusted life years (QALYs) over a 6-month period. PAT was not cost-effective unless therapists' (and drug) prices declined.

Baker-Jones, M., Carhart-Harris, R. L., Erritzoe, D., Ginige, I., Giribaldi, B., Martell, J., Murphy, R., Murphy-Beiner, A., Nutt, D. J., Shannon, L., Weiss, B.

This analysis of an RCT (n=59) investigates the impact of psilocybin-assisted therapy (PAT) and escitalopram on personality traits in patients with moderate-to-severe major depressive disorder over a 6-week trial period. Significant decreases in neuroticism, introversion, disagreeableness, and impulsivity, and increases in absorption, conscientiousness, and openness were observed in the PAT group, while similar changes were seen in the escitalopram group.

Becker, A. M., Duthaler, U., Eckert, A., Holze, F., Klaiber, A., Ley, L., Liechti, M. E., Straumann, I., Varghese, N.

This double-blind, randomised, placebo-controlled, crossover study (n=24) investigates the co-administration of MDMA (100mg) and LSD (100µg) compared to their individual use and placebo. Findings reveal that while the combination doesn't enhance the quality of subjective effects compared to LSD alone, it prolongs these effects, elevates plasma concentrations of LSD, and extends LSD's plasma elimination half-life. However, the combination also increases blood pressure, heart rate, and pupil size more than LSD alone. It does not improve the safety profile of LSD, indicating that combining MDMA and LSD may not offer substantial benefits over LSD alone in psychedelic-assisted therapy.

Turkia, M.

This case study (n=1) examines the therapeutic use of ayahuasca in a woman in her late thirties suffering from complex trauma, bipolar disorder, borderline personality disorder, and suicidality. Participation in multiple ayahuasca ceremonies led to significant alleviation of distress, resolution of suicidality, and recognition of her bipolar disorder diagnosis, though core trauma remained partially unresolved. A subsequent follow-up showed continued reduction in dissociative symptoms and noted positive effects of ayahuasca on other instances of psychosis and bipolar disorder. The study contributes to a better understanding of ayahuasca's potential in treating bipolar disorder and severe traumatization.

Daly, E., Malievskaia, E., McAlonan, G. M., Murphy, D. G. M., Puts, N. A., Whelan, T. P.

This protocol summary introduces the shiftability paradigm and the study 'PSILAUT' which aims to bridge the translational gap in autism research. The authors suggest that current pharmacological approaches targeting autism have failed due to the lack of direct experimental evidence on how neurochemical systems modulate information processing in the human brain. To tackle this, 'PSILAUT' uses psilocybin as a pharmacological probe to directly test the hypothesis that the serotonin system functions differently in autistic and non-autistic adults.

Baumgartner, M. R., Bavato, F., Beste, C., Cole, D. M., Coray, R., Friedli, N., Oeltzschner, G., Opitz, A., Quednow, B. B., Seifritz, E., Steuer, A. E., Stock, A-K., Werner, A., Zimmermann, J., Zölch, N.

This observational study (n=86) used proton magnetic resonance spectroscopy (MRS) to compare glutamate-glutamine complex (GLX) and γ-aminobutyric acid (GABA) concentrations in the brains of 44 chronic, but recently abstinent, MDMA users with 42 MDMA-naïve controls. The results showed elevated GLX levels in the striatum of MDMA users and no group differences in GABA concentrations, though a negative association with MDMA use frequency was found. These findings suggest that MDMA use affects not only serotonin but also striatum GLX and GABA concentrations, potentially offering new explanations for cognitive deficits observed in MDMA users.

Gandy, S., Harrild, F., Irvine, A., Luke, D., Watts, R.

This online survey study (n=272) explores the influence of psychedelic experiences on participants' connection with nature. Results reveal that participants with a pre-existing relationship with nature found psychedelics to strengthen this connection, while those without a prior connection felt psychedelics helped them bond with the natural world. The commonly reported transpersonal experience of 'interconnectedness' was associated with shifts in attitudes and behaviours. Participants also reported benefits from psychedelic experiences that took place in natural settings.

Arikci, D., Becker, A. M., Coviello, F., Dierbach, S., Duthaler, U., Eckert, A., Holze, F., Klaiber, A., Ley, L., Liechti, M. E., Luethi, D., Straumann, I., Thomann, J., Varghese, N.

This randomised, double-blind, placebo-controlled, cross-over study (n=32) investigated the effects of mescaline, LSD, and psilocybin at psychoactive-equivalent doses. The acute subjective effects of these substances were comparable, and all had moderate autonomic effects with minor differences in diastolic blood pressure and heart rate. Mescaline induced slightly more subacute adverse effects, and differences were found in the duration of action, with mescaline lasting the longest.

Dinkelacker, J., Pop, I.

This observational naturalistic study (n=18) of microdosers over a month finds that on the microdosing day and the day after participants reported higher state authenticity. The researchers also found that they engaged in more activities on both days, but satisfaction was only higher on the microdosing day itself.

Breeksema, J. J., Kamphuis, J., Kuin, B., Niemeijer, A. R., Schoevers, R. A., van den Brink, W., Veraart, J. K. E., Vermetten, E.

This qualitative interview study (n=17) of those receiving esketamine (35-210mg/70kg, 12x over 6w) for depression explores patients' experiences. Findings reveal highly variable effects of ketamine with common psychological distress, and central themes include perceptual effects, detachment, stillness and openness, mystical-type effects, fear and anxiety, feeling hungover and tired, and a neutralizing mood effect post-session. While patients reported several esketamine effects with psychotherapeutic potential such as increased openness, detachment, and mystical-type experiences, the study identifies a need for additional support due to the frequency and severity of the perceived distress during the treatment.

Anand, A., Barnett, B. S., Goes, F. S., Hu, B., Mathew, S. J., Murrough, J. W., Ostroff, R. B., Sanacora, G., Wilkinson, S. T., Wolski, K.

This open-label, randomised trial (n=403) compared the effectiveness of iv ketamine (35mg/70kg, 6x, 3w) and electroconvulsive therapy (ECT) in treating treatment-resistant major depression (TRD). The results showed that 55.4% of patients in the ketamine group and 41.2% in the ECT group responded to the treatment, indicating ketamine was noninferior to ECT. ECT was associated with a temporary decrease in memory recall, while ketamine was associated with dissociation. Both treatments had similar improvements in patient-reported quality of life, with ECT having musculoskeletal adverse effects.

Becker, A. M., Duthaler, U., Eckert, A., Erne, L., Holze, F., Klaiber, A., Ley, L., Liechti, M. E., Mueller, L., Rubin-Kahana, D. S., Straumann, I., Vandersmissen, A., Varghese, N., Vogt, S. B.

This double-blind, placebo-controlled crossover trial (n=27) investigated different intravenous DMT administration regimens, including placebo, low and high infusion (0.6-1mg/min), and bolus doses (15-25mg) combined with low and high infusion. The study found that bolus doses rapidly induced intense psychedelic effects, with infusions causing slowly increasing, dose-dependent effects.

Boehnke, K. F., Kruger, D. J., Lucas, P.

This cross-sectional online survey (n=1639) investigated self-reported changes in substance use associated with past or current psychedelic use. Results indicate that 43% reported decreasing or ceasing alcohol, cocaine, or antidepressant use. Conversely, the highest rates of increased use were reported for cannabis and tobacco products (10%). Key reasons for substance use reductions included increased self-connection, less anxiety or depression, and connection with nature and others. Factors leading to reduction in any substance use included the motivation to treat a medical condition, the number of psychedelics used, younger age, and using both microdoses and macrodoses.

Pleet, M. M., White, J., Yehuda, R., Zamaria, J. A.

This data analysis study (n=884) examines the impact of a psychedelic helpline on mitigating risks associated with nonclinical psychedelic use. The findings suggest that 65.9% of callers experienced a de-escalation in psychological distress due to the helpline. Additionally, 29.3% reported they could have been harmed, 12.5% might have dialed 911, and 10.8% could have visited an emergency room had it not been for their interaction with the helpline, implying the helpline may prevent harmful outcomes and alleviate strain on emergency and medical services.

Batievsky, D., Kaplan, S. B., Maglione, D. N., Thase, M., Vidot, D. C., Weiner, M.

This pilot study (n=10) examines the efficacy of ketamine-assisted psychotherapy (KAP) in individuals diagnosed with both chronic pain and major depressive disorder (MDD). The participants were divided equally into two groups: one receiving high-dose intramuscular ketamine before therapy (psychedelic approach) and the other receiving low-dose sublingual ketamine during therapy (psycholytic approach). No statistically significant difference between the groups was found, but both improved.

Abagyan, R., Dahill, D., de Boer, A., Jerome, L., Makunts, T.

This survey (n=17) investigates cardiovascular adverse events (AEs) associated with MDMA-assisted therapy sessions, utilizing the FDA Adverse Event Reporting System. The study finds that all cases of cardiovascular AEs involved using additional substances alongside MDMA, all of which had been previously associated with cardiovascular AEs. MDMA was not marked as the primary suspect in any of the reports.

Heifets, B. D., Hietamies, T. M., Klise, A. J., Levine, S. P., McInnes, L. A., Qian, J. J., Williams, L., Worley, M. J.

This retrospective controlled analysis (n=2758) conducted in ten community clinics across the US evaluates the impact of Ketamine Intravenous Therapy (KIT) on depression and anxiety symptoms. Results indicate significant reductions in both anxiety and depression symptoms post-induction (Cohen's d = 1.17 and d = 1.56, respectively) and greater depression symptom reduction at eight weeks compared to KIT-naive patients or those beginning standard antidepressant therapy (Cohen’s d = -1.03 and d = -0.62 respectively).

Arekapudi, A., Chau, E. H., Chisamore, N., Danayan, K., Di Vincenzo, J. D., Doyle, Z., Fancy, F., Kratiuk, K., Mansur, R. B., McIntyre, R. S., Meshkat, S., Phan, L., Rodrigues, N. B., Rosenblat, J. D., Tabassum, A.

This retrospective analysis (n=52) investigates the efficacy of ketamine (35-52mg/70kg; 4x) for treating treatment-resistant depression (TRD) in transitional age youth (TAY; age 18-25), comparing them with matched adults. The study finds significant reductions in depression, anxiety, and suicidal ideation in the TAY group, with effect sizes indicative of clinically meaningful improvements. The benefits and safety outcomes in the TAY group were comparable to the GA group, suggesting ketamine can be equally effective and well-tolerated in younger patients with TRD.

Atila, C., Christ-Crain, M., Eckert, A., Heinrichs, M., Holze, F., Hutter, N., Liechti, M. E., Murugesu, R., Rommers, N., Sailer, C. O., Varghese, N.

This double-blind, placebo-controlled study (n=30) explores oxytocin deficiency in patients with arginine vasopressin deficiency (central diabetes insipidus), using MDMA as a biochemical and psychoactive provocation test. The participants included patients with vasopressin deficiency and healthy controls, who were given either MDMA or placebo in a randomised order over two sessions.

Bornemann, J., Murphy, R., Murphy-Beiner, A., Schlag, A. K., Spriggs, M. J., Thurgur, H.

This theory-building article (2023) presents the ARC (Access, Reciprocity and Conduct) framework, a culturally informed ethical infrastructure for psychedelic-assisted therapy (PAT). The ARC framework emphasizes equitable access to PAT for mental health treatment needs, ensures safety in clinical contexts, and acknowledges the traditional and spiritual uses of psychedelic medicines. Developed using a dual-phase co-design approach, it invites contributions and feedback from stakeholders across research, industry, therapy, community, and indigenous settings to address the complex ethical questions arising in the rapidly expanding field of PAT.

Gan, Y., Hu, Z., Lan, X-F., Li, N., Li, W., Liu, H., Ning, Y-P., Wang, C., Wu, Z., Ye, Y., Zhang, F., Zhou, Y.

This re-analysis of an open-label study (n=103) investigated the effects of ketamine (35mg/70kg, 6x) on pain, depression, and social function in patients with bipolar or unipolar depressive disorder. The results showed that ketamine treatment significantly improved psychosocial functioning and reduced pain index. Mediation analysis revealed that the severity of depressive symptoms and the affective index of pain partially mediated the association between ketamine treatment and improvements in subjective and objective social functioning.

Bai, Y. M., Chen, L-F., Chen, M. H., Li, C. T., Li, W., Su, T. P., Tsai, S-J., Tu, P. C., Wu, H-J.

This double-blind, randomised study (n=48) involving patients with treatment-resistant depression (TRD) and suicidal ideation (SI) evaluated the effects of a single infusion of 35mg/70kg ketamine or 3.15mg/70kg midazolam. Using positron emission tomography-magnetic resonance imaging, the study observed a small but significant volumetric reduction in the right dorsolateral prefrontal cortex (DLPFC) in the ketamine group compared to the midazolam group, and a greater reduction in depressive symptoms was associated with smaller decreases in right DLPFC volumes.

Aggerwal, S., Deol, J. K., Di Virgilio, V., Gupta, G., Minerbi, A.

This pre-print of an observational study (n=65) examines the impact of psychedelic medicines on wellness among civilian or military veterans who self-identified as using these substances for non-recreational purposes in the past three years. Participants reported improvements in all domains (pain, mental health, function, and overall quality of life), with the highest perceived improvement in mental health and overall quality of life, and lowest in pain. The results suggest a significant association between the perceived changes in all domains, regardless of the specific psychedelic substance used.

Bradley, M. K., Dworkin, R. H., Johnson, M. W., Kleykamp, B. A., Nayak, S., Strain, E. C.

This systematic review (2023, s=86) of psychedelic RCTs (up to May 2020) finds that for placebo, 61% used an inert control, 20% active comparators (e.g. niacin), 15% both, and 4% a lower psychedelic dose. Of the 21 therapeutic trials, only 3 (14%) compared different amounts of therapy. Most studies were blinded, but less than 20% tested blinding (generally poor).

Hirschfeld, T., Majic, T., Prugger, J., Schmidt, T. T.

This study (n=322) analyses data from previous studies to assess the dose-response relationship and outcomes on the Altered States of Consciousness Rating Scale (ASC) and the Mystical Experience Questionnaire (MEQ) following LSD (25μg to 200μg) administration. Increasing doses were positively correlated with ratings on most factors and scales of the questionnaires, with the strongest responses for visionary phenomena such as audio-visual synesthesia and altered imagery, followed by positively perceived ego dissolution comprising depersonalization and derealization phenomena.

Bell, E., Cruz, N., Degutis, M., Do-Nguyen, K., Griffo, A., Howland, R. H., Keller, T. A., Kopelman, J., Mathew, S. J., Panny, B., Price, R., Spotts, C., Wallace, M. L.

This re-analysis of a randomised trial (n=98) investigates the impact of intravenous ketamine on rapidly reversing depression by enhancing neuroplasticity. The study found that greater decreases in mean diffusivity, a marker of microstructural neuroplasticity, from pre-infusion to 24-hour post-infusion were associated with larger improvements in depression scores.

Carhart-Harris, R. L., Monson, C. M., Wagner, A. C., Zeifman, R. J.

This re-analysis of the psilocybin (25mg) versus escitalopram (antidepressant, 6 weeks) RCT finds that in the psilocybin arm, experiential avoidance reductions led to improvements in mental health outcomes (e.g. depression severity). Note: the trial itself was insignificant on the primary measure of depression.

Howland, R. H., Mathew, S. J., Price, R., Wallace, M. L.

This follow-up to a randomised clinical trial (n=154) of adults with treatment-resistant depression (TRD) examined the impact of a digital intervention, automated self-association training (ASAT), on prolonging the antidepressant effect of a single ketamine infusion. The trial found that ketamine, followed by four days of ASAT, resulted in a significant effect on depression that lasted for three months, though the benefit was not sustained in months 4 to 12.

Bright, S. J., Bruno, R., Sharbanee, J. M., Skeffington, P. M., Thal, S., Wenge, T., Wieberneit, M.

This systematized review (s=82) examines the current evidence for best therapeutic practices during administration sessions with serotonergic psychedelics and entactogens (e.g. MDMA) as adjuncts to psychotherapy. The study finds that the effects of different therapeutic models, methods, techniques, and more complex interventions on therapeutic outcomes have not been investigated rigorously, with most available evidence being anecdotal.

Barnett, B. S., Hendricks, P. S., Sweat, N. W.

This case presentation (n=1) describes a subject with red-green colour vision deficiency (mild deuteranomaly) who experienced a partial improvement in their condition after using 5g of dried psilocybin mushrooms. Self-reported Ishihara Test data showed the improvement peaking at 8 days and lasting at least 16 days post-administration, although further observations were confounded by other substance use.

Caron-Lapointe, G., Joshi, K., Pilon, D., Shah, A., Teeple, A., Zhdanava, M.

This real-world (n=269) analysis of esketamine (Spravato) use finds nearly 50% of patients had their first pharmacy claim approved. Of those approved, 45% had eight or more treatment sessions (as recommended), though spread over 85 days (versus 28 per the label). Patients had lower health utilization, but this could be due to factors outside of the esketamine treatment (e.g. regression to the mean).

Carhart-Harris, R. L., Daws, R. E., Gazzaley, A., Girn, M., Rosas, F. E.

This commentary (2023) discusses the potential transdiagnostic efficacy of psychedelic-assisted therapy and its impact on brain function. It proposes that psychedelics induce a mode of brain function that is more dynamically flexible, diverse, integrated, and tuned for information sharing, which is consistent with greater criticality, and suggests that a complexity science perspective may help in understanding the inconsistencies in previous findings and guide towards compelling mechanistic models.

Kloft, L., Mallaroni, P., Mason, N. L., Ramaekers, J. G., Reckweg, J., Toennes, S. W., van Oorsouw, K.

This observational study (n=24) analysed mental imagery during ayahuasca use among Santo Daime church members. Results showed increased feelings of boundlessness and ego dissolution, correlating with peak DMT concentration, while mental imagery measures didn't significantly differ. The study suggests DMT drives the primary ayahuasca experience with long-term use possibly reducing its impact on mental imagery.

Cestac, P., de Laportalière, T. T., Jullien, A., Montastruc, F., Yrondi, A.

This systematic review (s=10 trials) evaluates the quality of adverse event (AE) reporting in published clinical trials studying esketamine for resistant depression. It reveals that 41.5% of serious AEs and 39% of non-serious AEs were not reported in the published articles compared to ClinicalTrials.gov, with the majority being psychiatric and cardiovascular events and 94% concerning patients from esketamine groups.

Bedford, P., Borgwardt, S., Diaconescu, A. O., Hauke, D. J., Holze, F., Ley, L., Liechti, M. E., Müller, F., Nagy-Huber, M., Roth, V., Vizeli, P., Wang, Z.

This brain modelling study used data from two double-blind, randomised controlled trials to model whole-brain effective connectivity (EC) data and compare it to the previously reported functional connectivity (FC) data gathered following LSD administration. LSD decreased brain connectivity and increased self-inhibition in certain brain regions. EC and FC offer promise as clinically-relevant biomarkers for LSD effects.

Anand, A., Carhart-Harris, R. L., Ertl, N., Kaelen, M., Lam, C., Nutt, D. J., Roseman, L., Wall, M. B.

This neuroimaging study (n=19) used fMRI and ALFF techniques to assess the brain's response to music after administering psilocybin to participants with treatment-resistant depression (TRD). A comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with the intensity of subjective effects felt during the dosing sessions implying an elevated response to music following psilocybin therapy.

Allen, G., Benway, T., Erritzoe, D., Good, M., Hughes, C., James, E., Joel, Z., Routledge, C., Timmermann, C., Topping, H., Weaver, R.

This double-blind, placebo-controlled study (n=24) evaluated the metabolism and clinical pharmacokinetics (how the body processes drugs) of DMT (SPL026) in an ongoing Phase I study with healthy subjects by Small Pharma. Participants received escalating doses of SPL026 via a 2-phase intravenous (IV) infusion. SP206 was safe and well-tolerated, and dose-proportional increases in DMT exposure were observed over 9-21.5 mg. For all doses, the median time to peak plasma concentration was ~10 min, and the mean elimination half-life was 9-12 min.

Barron, J., Boehnke, K. F., Enghoff, O., Herberholz, M., Kruger, D. J.

This online survey (n=1221) examines people's information-seeking behaviour using psychedelics naturally, revealing that most participants rely on their own experimentation and experiences, Internet websites, friends, discussion forums, books, and scientific journals. The study also found that articles in scientific journals, psychedelic nonprofits, and university researchers were the most trusted sources, while government agencies and pharmaceutical companies were the least trusted.

Gerlach-Houck, H., Gold, N. D., Goldway, N., Jackson, E. S.

This pre-print analysis of online (Reddit) posts finds that classical psychedelics benefited 75% of those who mentioned the effects (10% negative). The benefits spanned behavioural change (e.g. reduced stuttering), emotional benefit, and cognitive changes.

Bains, R., Bennett, J. N., Blough, M. D., Galloway, L., Mitchell, I.

This pre-print open-label trial (n=14) organised by ATMA Journey Centers finds psilocybin to be safe, with peak systolic (146) and diastolic (94) blood pressures to be within acceptable ranges. Secondary analyses find a significant decrease in depression (QIDS-SR16) and high mysticism scores (MEQ-30).

Amarneh, D., Averill, L. A., Iqbal, S., Lijffijt, M., Mathew, S. J., Murphy, N., O'Brien, B., Swann, A. C., Tamman, A. J. F.

This re-analysis from a randomised control trial (n=33) investigates the effects of IV ketamine or midazolam (active control) on military veterans with late-in-life treatment-resistant depression using two EEG neural complexity markers (Lempel-Ziv complexity and multiscale entropy). The study found that both complexity markers increased 30 minutes post-infusion, with time-varying effects on system-wide contributions to the evoked glutamatergic surge. Still, no relationship was observed between complexity and reduction in depressive symptoms.

Lake, S., Lucas, P.

This survey (n=2045) of Canadian psychedelic users finds psilocybin, MDMA and LSD are the most commonly used. It also reports positive (82%) life changes and challenging experiences (52%). Motivations for use include fun, self-exploration, general mental well-being, and personal growth.

Carhart-Harris, R. L., Cofre, R., Herzog, R., Lodder, P., Mediano, P. A. M., Perl, Y. S., Rosas, F. E., Tagliazucchi, E.

This whole-brain simulation reproduces earlier studies where increased entropy was found under the influence of psychedelics. The changes weren't uniform, with larger effects in the optical area. The changes were not well-explained by looking at where the most serotonin (2a) receptors were but mapped closely to the topological (spatial) properties of how the brain is connected.

Chauhan, S., Chen, Y., Cruz, E. D. L., Datta, M. S., Gong, C., Tomer, R., Zhang, J.

This pre-print brain-mapping study in mice (2023) shows that repeated ketamine administration decreases dopamine neurons in the midbrain and increases in the hypothalamus. It also reveals further evidence for the plasticity-increasing effects of ketamine.

Family, N., Luke, D. P., Murray-Lawson, C., Sadibolova, R., Terhune, D. B., Williams, L. T. J.

This pre-print re-analysis (n=48) of microdosing LSD (5-20μg) finds that LSD reduces the influence of our expectations (precision-weighted local priors) on what we think time should feel like (under-reproduction bias). When controlling for the expectations, the bias disappears, indicating that LSD microdosing reduces the relative weighting of priors (expectations).

Jones, J. L.

This survey (n=918) of self-reported substance abusers finds that the majority support research into MDMA-assisted therapy (68%). Six out of ten would be willing to try it if appropriate for their situation.

Al-Sharif, N. B., Espinoza, R. T., Joshi, S. H., Khalil, J., McClintock, S. M., Narr, K. L., Taraku, B., Zavaliangos-Petropulu, A.

This open-label study (n=66) finds that four ketamine infusions (35mg/70kg) led to improvements in cognition both immediately (measured after the first and fourth infusion) and up to five weeks later. As seen in other studies, antidepressant effects reverted to baseline at five weeks.

Andrade, C., Faheem, A., Menon, V., Varadharajan, N.

This systematic review & meta-analysis of five RCTs (ketamine: n=141; ECT: n=137) compared the efficacy & safety of ketamine and electroconvulsive therapy (ECT) in adults with major depressive episodes. The results suggested that ECT was superior to ketamine in post-treatment depression ratings, response rates, and remission rates one week after treatment. However, there was no significant difference between the groups in the number of sessions to response and remission or cognitive outcomes.

Dai, R., Harris, R. E., Huang, Z., Hudetz, A. G., Janke, E., Larkin, T. E., Mashour, G. A., McKinney, A., Picton, P., Tarnal, V., Vlisides, P. E.

This fMRI analysis study (n=74 total) looks at how three different drugs -; nitrous oxide, ketamine, and lysergic acid diethylamide (LSD) -; affect the way different parts of the brain communicate with each other. By comparing brain scans taken before and during drug use, the study found that all three drugs reduced connectivity within certain networks in the brain, while enhancing connections between different networks. These effects were seen in areas of the brain that are important for our conscious experiences.

Casanova, A., Casarotto, S., Ort, A., Preller, K. H., Sarasso, S., Seifritz, E., Smallridge, J. W., Tononi, G., Vollenweider, F. X., von Rotz, R.

This double-blind cross-over brain imaging study (n=22) of psilocybin combined EEG with transcranial magnetic stimulation (TMS) to reveal that psilocybin produces a chaotic pattern of brain activity (versus placebo; LZc complexity under eyes closed). Using TMS, the authors could measure the Perturbational Complexity Index (PCI) due to the stimulation. The difference between psilocybin and placebo on PCI wasn't significant.

Girn, M., Mosurinjohn, S., Roseman, L.

This review (2023) discusses the limitations and biases in using psychometric assessments to measure mystical experiences in psychedelic research. The authors argue that the existing operationalizations of mystical experiences fail to acknowledge their Christian bias and suggest more culturally-sensitive approaches. They also propose complementary non-mystical approaches to understanding similar phenomena for more robust theoretical and empirical approaches.

Alexander, L., Hartland, H., Jelen, L. A., Strawbridge, R., Young, A. H.

This meta-analysis (s=14) of ketamine's anti-anxiety (anxiolytic) effects finds immediate (within 12 hours) effects lasting up to two weeks.

Campbell, W. K., Miller, J. D., Sleep, C., Weiss, B.

This interview study (n=110) finds non-significant positive changes in self-reported narcissism after ceremonial ayahuasca use.

Sjöstedt-Hughes, P.

This hypothesis paper (2023) proposes integrating metaphysical experiences from psychedelic-assisted therapy with metaphysics, offering a Metaphysics Matrix and Metaphysics Matrix Questionnaire to aid in this process. By fusing philosophy with practical science, the text argues that patients may receive additional benefits during the integrative phase of therapy.

Bai, D., Canuso, C. M., Chen, X., Fu, D. J., Hou, X., Lane, R., Wang, G., Zhang, C.

This double-blind, randomised Phase III trial (n=227) finds no significant difference between esketamine plus a new antidepressant versus only the antidepressant (and a placebo) at day 28 on depression scores (MADRS). The study reports one death in the esketamine group. It also states esketamine to be effective and safe though only the first claim could be credibly made if one only looks at the immediate (24-hour) effects.

Chambers, R., Goldberg, S. B., Hendricks, P. S., Osika, W., Ryde, A., Schlosser, M., Simonsson, A., Simonsson, O.

This survey study (n=2822) finds a correlation between lifetime classical psychedelic use (n=613) and a higher frequency of current mindfulness meditation (but not compassion meditation) practice. When analysing psychological insight (an aspect of the acute psychedelic experience), a correlation with both types of meditation was found.

Carhart-Harris, R. L., Chiacchiaretta, P., Ferretti, A., Nutt, D. J., Onofrj, M., Penna, S. D., Pizzi, S. D., Roseman, L., Sensi, S. L., Sestieri, C., Timmermann, C.

This analysis of resting-state fMRI (n=15) of LSD (75μg) effects on the brain finds modifications in serotonin receptor-rich areas. The local signal amplitude and functional connectivity (FC) increased in the default mode network (DMN) and attention networks (rich in serotonin 2a receptors). A decrease was seen in limbic areas (with many serotonin 1a receptors).

Simonds, C. H.

This paper explores integrating Tibetan Buddhist contemplative tradition with psychedelic-assisted therapy (PAT), highlighting the absence of contemplative traditions in current psychedelic therapy discourse. By comparing phenomenological similarities between Tibetan Buddhist meditation and psychedelic experiences, the paper suggests that incorporating the Tibetan framework of view, meditation, and action may enhance the efficacy of PAT.

Cornejo, G., Feusner, J. D., Gomez, G. J., Hellerstein, D. J., Naraindas, A. M., Schneider, F., Wheaton, M. G.

This open-label study (n=12) of patients suffering from Body dysmorphic disorder (BDD), an obsessive preoccupation with misperceptions of appearance, finds that psilocybin (25mg) plus psychological support (6 sessions) resulted in a response (>30% decrease in BDD-YBOCS) in 58% of participants. Secondary measures such as negative affect, disability, and conviction of belief also significantly decreased.

Cavadino, A., Evans, W. J., Forsyth, A., Godfrey, K., Hoeh, N. R., Krishmamuthy, V., Menkes, D. B., Murphy, R., Muthukumaraswamy, S., Ponton, R., Smith, T., Sumner, R. L.

This placebo-controlled, randomised, naturalistic study (n=80) of repeated microdoses of LSD (10μg, 14x, 6w) finds improved ratings, on dosing days, on creativity, connectedness, energy, and other wellness ratings. Though these transient changes were found, no enduring changes to mood and cognition were observed.

Evans, J.

This essay (2023) discusses evolutionary spirituality, a cultural frame for psychedelics in western culture, which suggests that human evolution can be guided towards creating higher beings through techniques like psychedelics and eugenics. It identifies five ethical limitations of this tradition, including spiritual narcissism and contempt for less-evolved masses, before suggesting responses to these limitations.

Luke, D., Michael, P., Robinson, O.

This naturalistic qualitative study (n=36) explored the phenomenology of the 'self' during breakthrough DMT experiences (40-75 mg inhaled) in home settings. Thematic analysis identified five distinct categories of effects: onset transitions, bodily sensations, sensorial alterations, psychological shifts in memory or language, and deep emotional impact.

Bai, Y. M., Chen, L-F., Chen, M. H., Lin, W. C., Mao, W-C., Su, T. P., Tsai, S-J., Tu, P. C., Wu, H-J.

This randomised study (n=84) investigated the benefits of low-dose ketamine (35mg/70kg) for patients with treatment-resistant depression (TRD) and prominent suicidal ideation. The study found ketamine safe, tolerable, and effective treatment for TRD and suicidal ideation.

de Araujo, D. B., Hövel, P., Onias, H., Palhano-Fontes, F., Soldatkina, O., Viol, A., Viswanathan, G. M.

This re-analysis (n=7) found that ingesting ayahuasca (100-120ml) led to an increase in the average information parity in the brain networks of individuals, particularly in the limbic system and frontal cortex regions. By comparing resting-state functional brain networks of individuals before and after ingesting ayahuasca, the study utilized complex network theory and calculated pairwise information parity to quantify functional, statistical symmetries between brain region connectivity.

Holiday, C., Joshi, K., Karkare, S., Pilon, D., Shah, A., Zhdanava, M.

This analysis of health outcomes (n=269) of those treated with esketamine for treatment-resistant depression (TRD) finds a trend (but not significant differences) towards lower healthcare costs. Dosing intervals (of ketamine) were longer than recommended on the label.

D’Souza, D. C., Pathania, S., Pittman, B. P., Safi-Aghdam, H., Skosnik, P. D., Sloshower, J. A., Syed, S. A.

This single-blind, placebo-controlled study (n=19) of psilocybin (21mg/70kg) in combination with therapy (ACT, 8x) finds an improvement in depression scores. However, the difference between the psilocybin and placebo groups was insignificant. Though the study tried to control for expectancy (placebo) effects, participants (80%) correctly guessed if they received psilocybin.

Alamia, A., Carhart-Harris, R. L., Erritzoe, D., Girn, M., Haridas, S., Kettner, H., Leech, R., Luan, L., Martell, J., Nutt, D. J., Pallavicini, C., Rosas, F. E., Roseman, L., Tagliazucchi, E., Timmermann, C.

This neuroimaging study (n=20) aimed to understand the effects of DMT (20mg) on the human brain. The researchers used EEG-fMRI (electroencephalography-functional MRI) to measure brain activity before, during, and after administering DMT to healthy volunteers. They found that DMT increased global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient.

Copello, A., Fox, A. P., Ryan, R. S.

This text-based interview study (n=13) explores the experiences and perceived mental health and well-being changes of microdosing psychedelics. The results identified three superordinate themes: 1) Seeking a solution: Agency and rationale; 2) Microdosers as scientists; 3) Catalysing desirable and beneficial effects.

Mash, D. C.

This review (2023) gives an overview of research into ibogaine. It details animal studies and the human use of ibogaine in stopping addiction. Studies are few and far between, and clinical trials are only now being started.

Arekapudi, A., Chau, E. H., Chisamore, N., Danayan, K., Di Vincenzo, J. D., Doyle, Z., Fancy, F., Kratiuk, K., Mansur, R. B., McIntyre, R. S., Meshkat, S., Phan, L., Rodrigues, N. B., Rosenblat, J. D., Tabassum, A., Teopiz, K. M.

This retrospective analysis (n=100) of the effectiveness of ketamine (35mg/70kg) for borderline personality disorder (BPD) in those with treatment-resistant depression (TRD) finds that intravenous ketamine significantly reduces symptoms of depression, borderline personality, suicidality, and anxiety in patients with comorbid BPD and TRD. Both BPD-positive and BPD-negative groups showed significant improvements in the primary outcome measures, with no significant difference between groups.

Leal, G. C.

This double-blind, cross-over study (n=10) finds that arketamine (35mg/70kg, the 'right-handedness of ketamine) isn't superior to placebo, but does find it to be safe in a population with treatment-resistant depression (TRD).

Ferris, J. A., Kopra, E., Kuypers, K. P. C., Rucker, J., Winstock, A. R., Young, A. H.

This analysis of survey data (n=3364, Global Drug Survey 2020) finds a positive relationship between LSD and psilocybin use for self-treatment, and well-being outcomes, particularly insight and mood. A quarter of respondents reported adverse effects.

Abizaid, A., Aguilar-Valles, A., Arsenault, E., Bautista-Carro, A., Bonniwell, E. M., Calkins, M. M., Cao, A. B., El Sayegh, F., Ghaffari, A., Halberstadt, A. L., Lanham, J. K., Lewis, V., Malcolm, N. J., McCorvy, J. D., Morton, K., Schmid, Y., Sheshbaradaran, H., Taghavi-Abkuh, F-F., Telfer, A.

This mice and cell study of the non-hallucinogenic LSD analogue 2-bromo-LSD (2-Br-LSD) found it to be a partial agonist at the 5-HT2A receptor but it doesn't activate the 5-HT2B receptor associated with cardiac valvulopathy (disease of heart valves). It also does not induce tolerance and has been shown to promote neuronal structural plasticity and active coping behaviour in mice. Additionally, 2-Br-LSD reverses the effects of chronic stress. These findings suggest that 2-Br-LSD may have therapeutic potential for mood disorders and other indications.

Kangaslampi, S.

This review (2023, s=44) synthesizes the evidence for the association between mystical-type experiences and improvements in well-being and mental health. It finds the strongest evidence in cross-sectional studies and healthy people. Some studies suggest that psychological insight and emotional breakthroughs may be similarly or more closely associated with positive changes than mystical-type experiences.

Kinderlehrer, D. A.

This case study (n=1) describes an immunocompetent male with neuropsychiatric Lyme disease who did not respond to conventional treatments. However, his symptoms improved when he started using psilocybin in sub-hallucinogenic doses. Psilocybin is both serotonergic and anti-inflammatory, which may benefit patients with mental illness secondary to autoimmune inflammation.

Aaru, J., Kaup, K. K., Pikame, J., Tulver, K., Vasser, M.

This open-label study (n=12) assed the ability of Psyrreal, a VR experience that mimics the phenomenological components of psychedelic and mystical experiences, in alleviating depressive symptoms in people with mild-to-moderate depression. Results suggest that VR-augmented therapy could be beneficial in treating depressive symptoms, with participants showing a significant reduction in depressive symptoms two weeks after the experiments.

Brasher, T., Rosen, D., Spinella, M.

This survey study (n=3157) investigated the effects of classical psychedelic use on psychological well-being in the general population. The results showed that classical psychedelic users exhibited greater psychological strengths and well-being and lower levels of distress compared to cannabis and alcohol users. The benefits were mediated by self-transcendence and motivated by personal growth, regardless of demographic variables, beliefs about psychedelics, and other drug use.

Calder, A. E., Hasler, G., Oehen, P., Ponomarenko, P., Seragnoli, F.

This article discusses the therapeutic potential of psychedelic-assisted group psychotherapy (PAGP), which has received less attention than individual psychedelic-assisted psychotherapy models. The authors analyse current literature and use Irvin Yalom's 11 therapeutic factors of group therapy as a framework to discuss the benefits of PAGP, including increased group connectedness and interpersonal learning.

Abbas, A., Bartlett, L., Bretton-Granatoor, Z., Firdous, A., Harris, A., Olson, R., Sonneborn, A.

This pre-print (2023) rodent study found that DOI caused changes in brain activity (specifically the mPFC) that differed from normal patterns. During rest, when brain activity is usually synchronized, the drug causes a decrease in synchronization and an increase in gamma activity.

Barriocanal, A. M., Busardo, F., Carabias, L., de la Rosa, G., Farré, M., Fonseca, F., Hladun, O., Kelmendi, B., Martín, S., Núñez-Montero, M., Papaseit, E., Pérez-Mañá, C., Pichini, S., Poyatos, L., Taoussi, O., Torrens, M.

This double-blind study (n=17) compared the pharmacological effects of methylone (200mg) and MDMA (100mg), for which methylone is a popular substitute. The results showed that methylone could significantly increase blood pressure and heart rate and induce pleasurable effects similar to MDMA, including stimulation, euphoria, well-being, enhanced empathy, and altered perception.

Choi, E. Y., Corlett, P. R., Dhaliwal, K., Fineberg, S. K., Krystal, J. H., Neustadter, E., Null, K., Peters, J. R., Pittaro, G. F., Rondeau, J., Sakheim, M., Shapiro-Thompson, R., Trujillo-Diaz, D.

This randomised controlled trial (n=22) is the first to study ketamine (35mg/70kg) in Borderline (BPD) in a placebo-controlled study. The study didn't report statistically significant differences between the ketamine and midazolam (active placebo) groups, though it did show a positive trend.

Cameron, L. P., Carter, S. J., Dong, C., Dunlap, L. E., Gray, J. A., Hennesssey, J. J., Jami, S. A., McCorvy, J. D., Olson, D. E., Patel, S. D., Saeger, H. N., Tian, L., Tombari, R. J., Vargas, M. V.

This series of experiments in mice (in vivo) and human cells (in vitro) found that a specific type of receptor called intracellular serotonin 2A receptor is partially responsible for neuroplasticity (growth-promoting effect). This suggests that intracellular, versus that on the surface of a neuron, serotonin 2A receptors could be a target for developing new therapies and that there is still much to be learned about how psychedelics (and other drugs) work in the brain.

Kuypers, K. P. C., Mallaroni, P., Mason, N. L., Paci, R., Ramaekers, J. G., Reckweg, J., Theunissen, E. L., Toennes, S. W.

This double-blind study (n=22) compares the effect of 2C-B (20mg) and psilocybin (15mg). It finds that 2C-B elicited alterations in consciousness of a psychedelic nature but with a shorter duration of self-reported effects than psilocybin. The study categorised 2C-B (at least at that dose) as a subjectively lighter psychedelic.

Aday, J. S., Bradley, E. R., Eaton, N., Fredenburg, L., Fernandes-Osterhold, G., Mantia, J., Pleet, M. M., Skiles, Z., Woolley, J. D.

This survey (n=32, of 145 sent out) of Usona Phase II trial therapists finds that most (88%) had personal experience with psychedelics (e.g. psilocybin). The reasons for use were diverse, ranging from personal development to fun.

Aggerwal, S., Deol, J. K., Di Virgilio, A., Di Virgilio, V., Fletcher, J., Gupta, G., Minerbi, A., Sheen, L.

This preprint qualitative analysis (n=65) of civilians and veterans finds improvements in wellness (a term used by the WHO), which includes improvements in medical and mental health conditions, social interactions, spirituality, and overall function.

Gao, Z., Winhusen, T. J., Gorenflo, M., Ghitza, U. E., Davis, P. B., Kaelber, D. C., Xu, R.

This analysis of ketamine data (3800 patients who received ketamine for anaesthesia, and the same number of controls) suggest that ketamine may be useful for treating cocaine use disorder (CUD).

Abi-Gerges, N., Ansonoff, M., Bechand, B., Havel, V., Hemby, S. E., Hodges, A., Hunkele, A., Hwu, C., Javitch, J. A., Katritch, V., Kruegel, A. C., Majumdar, S., McIntosh, S., Nelson, M., Pintar, J. E., Sames, D., Stallings, L., Wulf, M. G., Yang, M., Zaidi, S. A.

This preprint (2023, v2) animal in vivo and human in vitro study examines a new class of oxa-iboga alkaloids (10 & 40 mg/kg) concerning their effects on opioid addiction in rats and their cardiotoxic effects on human heart cells. In contrast to noribogaine, oxa-iboga analogs exhibited no risk of inducing arrhythmia in adult human primary cardiomyocytes, and oxa-noribogaine induced acute and long-lasting suppression of morphine self-administration in rats in response to both single and repeated dosing regimes.

Lagopoulos, J.

This analysis of EEG data (n=25) from a study that used repeated ketamine oral tablets (6x, flexible dosing) for treating depression (MDD) found significant changes in alpha (during), theta and low-beta frequencies (after) brainwaves.

Jones, G. M., Lipson, J., Wang, E.

This survey study (n=214k; NSDUH) finds lowered odds on three out of four social impairment measures in those who use MDMA (lifetime use; correlational). Only mescaline also showed a relationship with reduced odds of difficulty dealing with strangers (one of the measures), but other (classical) psychedelics studied showed no relationship with the social impairment measures.

Aislaitner, G., Balabanov, P., Bałkowiec-Iskra, E., Butlen-Ducuing, F., Elferink, A., Haberkamp, M., Knudsen, G. M., Lundberg, J., Mattila, T., McCulloch, D. E-W., Stenbæk, D. S., Thirstrup, S.

This commentary (2023) showcases the support, and open questions, from the European regulatory perspective. It highlights the difficulties facing psychedelic trials (e.g. blinding), and showcases the support EMA can offer in ensuring the trials get done in a way that will lead to regulatory approval.

Ashton, M., Carhart-Harris, R. L., Eckernäs, E., Röshammar, D., Timmermann, C.

This re-analysis (n=13) of EEG (brain activity over time) data whilst under the influence of DMT (7-20mg iv) is the first to show a concentration-dependent suppression of alpha power (brain waves), which was partially true for beta power too. The (Lempel-Ziv) complexity of brain signals increased whilst under the influence of DMT.

van der Meer, P. B., Fuentes, J. J., Kaptein, A. A., Schoones, J. W., de Waal, M. M., Goudriaan, A. E., Kramers, K., Schellekens, A., Somers, M., Bossong, M. G., Batalla, A.

This review (2023, s=4) finds that only 151 patients (and one clinical trial) have been through trials with psilocybin (6-40mg) for addiction (alcohol & smoking). Still, the findings were positive and larger trials are underway.

Devenot, N., Garcia-Romeu, A., Johnson, M. W., Noorani, T. N., Seale-Feldman, A., Smith, E.

This analysis of the therapeutic frameworks used in psychedelic-assisted treatment (for smoking cessation specifically) finds that suggestions from the framework map onto outcomes (and the language used by participants) from the study. This has broader implications for psychedelic-assisted therapy, as suggestions (in the therapeutic framework) can be used for various purposes (positive and negative).

Cahn, B. R., Green, J. M., Harrison, C., Kelmendi, B., Lewis, C. R., Rabin, D. M., Spencer, S., Tafur, J., Yazar-Klosinski, B., Yehuda, R.

This pilot sub-study (MDMA, n=16; placebo, n=7) examined epigenetic changes in three hypothalamic-pituitary-adrenal (HPA) genes before and after MDMA-assisted therapy for post-traumatic stress disorder (PTSD). Methylation changes at 37 out of 259 CpG sites predicted symptom reduction, with one site in the NR3C1 gene showing greater methylation change in the MDMA treatment group compared to placebo.

Goodwin, G. M.

This re-analysis of the COMPASS Phase IIb RCT with psilocybin (25/10/1mg; COMP360) finds significantly higher scores on patient-reported depression severity, anxiety, positive affect, functioning, quality of life, and cognitive function. Though the main finding of the study was less impressive than hoped, all patient-reported measures show that the high dose of psilocybin (25mg) led to better outcomes.

Borkel, L. F., Henríquez-Hernández, L. A., Quintana-Hernández, D. J., Rojas-Hernández, J.

This review (s=33) of psychedelic compounds (e.g. LSD & psilocybin) finds that they aren't addictive or toxic at low doses, but can be harmful at high doses. Physiologically the biggest risk was identified for MDMA, though psychological (relating to set & setting) risks may be more critical.

Carhart-Harris, R. L., Damiani, G., Deckersbach, T., Deco, G., Deco, N., Kiani, N., Kringelbach, M. L., Lozano-Soldevilla, D., Ponce-Alvarez, A., Rosas, F. E., Ruffini, G.

This preprint (2022) uses the Ising model of brain phase transition to assess fMRI BOLD data from a study in LSD was administered (n=15). Several different concepts from statistical physics were applied to the fMRI data to analyze individualized Ising temperature increases under the influence of LSD and placebo, showing that LSD ingestion shifts the system away from the critical point between paramagnetic and ferromagnetic phases to a more disordered state. Overall findings suggest that LSD increases the complexity of brain dynamics.

Arena, A. F., Foy, Y., Menzies, R. E., Moreton, S. G.

This survey study (n=201) finds that reductions in death anxiety mediated the effects of the (acute) mystical experience on life satisfaction. Death anxiety did not mediate any of the effects of psychological insight.

Lan, X-F., Wang, C., Zhou, Y.

This open-label study (n=39) of ketamine (35mg/70kg infusion, x6) for major depressive disorder (MDD) found that after ketamine treatment, the resting-state functional connectivity (RSFC) between the left amygdala and the left medial superior frontal gyrus of MDD patients increased significantly. This change was positively correlated with a reduction in depressive symptoms.

Garcia-Romeu, A., Mathai, D. S., Nayak, S., Yaden, D. B.

This post hoc analysis (n=576) examined the relationship between acute dissociation and the antidepressant efficacy of esketamine in treatment-resistant depression by combining data from the TRANSFORM-1 and TRANSFORM-2 clinical trials. It found no clinically significant association between dissociation and antidepressant effect for esketamine, suggesting the need for improved characterization of drug experiences relevant to therapeutic outcomes.

Aripaka, S. S., Burmester, D., Elfving, B., Fisher, P. M., Frokjaer, V. G., Knudsen, G. M., Madsen, M. K., Mikkelsen, J. D., Stenbæk, D. S., Szabo, A.

This open-label study (n=16) assessed the effects of a single dose of psilocybin (15mg/70kg) on biomarkers of inflammation in healthy participants. Blood samples before and one day after the administration revealed that psilocybin did not significantly impact any of the selected biomarkers.

Dolder, P. C., Gasser, P., Holze, F., Liechti, M. E., Müller, F.

This double-blind cross-over trial (n=42) finds that LSD (2x 200 μg) significantly reduced anxiety (STAI-G) scores up to three months after treatment. The patients, both with and without a life-threatening illness, also improved on measures of depression (HAM-D, BDI). Those with more subjective drug effects and mystical-type experiences had better outcomes.

Averill, L. A., Davis, A. K., Polanco, M., Sepeda, N. D., Xin, Y.

This prospective study (n=86) evaluated the effects of ibogaine & 5-MeO-DMT treatment on risky alcohol use & PTSD symptoms among US Special Operations Forces Veterans. It found a significant reduction in alcohol use from pre-treatment to 1-month, 3-months, and 6-months post-treatment, and large differences between responders and non-responders in PTSD symptom and cognitive functioning change, suggesting that psychedelic-assisted therapy may hold promise for individuals with complex trauma and alcohol misuse.

day, K., Perkins, D., Rubiano, D. P., Ruffell, S. G. D., Sarris, J.

This theory-building article (2023) proposes a model of psychotherapeutic processes associated with ayahuasca consumption. It identifies five key effects: somatic effects, introspection and emotional processing, increased self-connection, increased spiritual connection, and gaining of insights and new perspectives.

Chambers, R., Goldberg, S. B., Hendricks, P. S., Osika, W., Simonsson, O.

This survey study (n=2822) examined the prevalence and associations of challenging, difficult, or distressing experiences using classic psychedelics in a subsample of respondents (n=613) who reported lifetime classic psychedelic use. Of those, 59% indicated no challenging experiences, 9% indicated having a difficult experience lasting more than one day, and 2.6% reported seeking medical/psychiatric/psychological assistance.

Adapa, R., Allanson, J., Atasoy, S., Carhart-Harris, R. L., Craig, M. M., Finoia, P., Kringelbach, M. L., Luppi, A. I., Manktelow, A. E., Mediano, P. A. M., Menon, D. K., Pappas, I., Peattie, A. R. D., Pickard, J. D., Roseman, L., Sahakian, B. J., Stamatakis, E. A., Vohryzek, J., Williams, G. B.

This theory-building paper (2023) shows that structure-function coupling (patterns of brain activity) is a generalisable indicator of consciousness. An increase in functional coupling indicates a loss of consciousness (e.g. brain-inured patients or anaesthesia), and opposite changes (decoupling of brain function from structure) are seen under the influence of psychedelics (e.g. LSD or ketamine).

Aaronson, S. T., Kirlic, N., Lennard-Jones, M., Miller, T. M., Modlin, N. L., Rucker, J., Schlosser, D.

This theory-building article (2023) proposes that a patient's 'readiness' (eligibility & capacity) is taken into account to optimise the outcomes of psilocybin/psychedelic-assisted therapies (PAT). Factors discussed include intrapersonal (e.g. openness & motivation) and interpersonal (e.g. therapeutic alliance) factors.

Gukasayan, N., Narayan, S. K.

This interview study (n=3) examines menstrual changes after using classical psychedelics. It finds 1) resumption of menstruation, 2) earlier menstruation, and 3) improved menstrual regularity. A possible underlying mechanism is the (in)direct effects of 5-HT2a agonism on the hypothalamic-pituitary-gonadal axis.

Areesanan, A., Gründemann, C., Liechti, M. E., Rudin, D.

This cell study finds no (negative) effect of classical psychedelics on T cell and monocyte immune responses. This indicates that they can be used by people with life-threatening diseases who are immunocompromised.

Araújo, D. B., Daldegan-Bueno, D., Falchi, M., Feilding, A., Mota, N., Olivieri, R., Palhano-Fontes, F., Ribeiro, S., Tófoli, L.F., Wießner, I.

This double-blind cross-over study (n=24) of a low/moderate dose of LSD (50μg) on the structure of language finds simpler and semantically more similar language after LSD.

Armeni, P., Costa, F., Falivena, C., Rognoni, C.

This economic analysis (Markov modelling) of esketamine treatment for depression (TRD) in Italy shows that it may be cost-effective from a societal perspective.

Beck, A., Byrne, K., Garland, E. L., Lewis, B. R., Thielking, P.

This qualitative survey (n=10) from patients who underwent psychedelic-assisted therapy (PAT) with psilocybin (25mg) for depression associated with a cancer diagnosis (HOPE trial) provides information on group format PAT, which participants rated highly.

Chen-Li, D., Di Vincenzo, J. D., Fancy, F., Haikazian, S., Johnson, D., Mansur, R. B., McIntyre, R. S., Meshkat, S., Rosenblat, J. D.

This systematic review (2023) finds that oral ketamine (35mg-85mg/70kg) has antidepressive effects, but that the evidence (n=2336, s=22) is still quite limited (only 4 RCTs with a high chance of bias).

Dinkelacker, J., Pop, I.

This observational naturalistic study (n=18) on microdosing found that it led to a decrease in positive and overall emotional diversity (emodiversity). Participants experienced more awe, wonder, or amazement and ashamed, humiliated, or disgraced emotions during microdosing days and fewer joyful, glad, or happy emotions.

Evans, J., Lutkajtis, A.

This interview study (n=30) investigates the experience of those who attended a psilocybin truffle retreat in The Netherlands. It finds that 30% experienced challenges in integration (e.g. spiritual bypass, lack of support) which also correlated with positive after-effects including long-term remission of significant health conditions.

McIntyre, R. S.

This open-label study (n=70) compared the effect of esketamine (28-84mg; 8x) in those with bipolar treatment-resistant depression (B-TRD, n=35) and those with unipolar TRD. There was no significant difference between the two groups on depression scores, and both responded to treatment. Those in the B-TRD group had more anxiety-reducing effects. This study is part of the REAL-ESK study.

Chmielewska, Z., Cubała, W. J., Galuszko-Wegielink, M., Jakuszkowiak-Wojten, K., Wiglusz, M. S.

This case series (n=4) reflects on the use of ketamine (35mg/70kg, up to 8x) as an adjunct treatment for psychotic treatment-resistant depression (TRD). It finds that all participants were in remission after treatment and that suicidal ideation went down.

Coker, A., Doblin, R., Emerson, A., George, M. S., Hanlon, C., Kuceyeski, A., Mithoefer, A. T., Mithoefer, M. C., Mithoever, O., Singleton, S. P., Wang, J. B., Yazar-Klosinski, B.

This follow-up analysis (n=9), of fMRI data from veterans and first responders who underwent MDMA-assisted therapy (3x 100-125mg) for PTSD, finds a correlation between reductions in PTSD and 1) increased amygdala-hippocampal connectivity, and 2) reduced amygdala-precuneus connectivity during memory recall.

Barragan, E. V., Cameron, L. P., Chow, W. L., Gray, J. A., Olson, D. E., Patel, S. D., Saeger, H. N., Vargas, M. V., Warren, H. T.

This rodent study suggests that activating serotonin 2A receptors is essential for tryptamine-based psychedelics to produce antidepressant-like effects in rodents. The study also suggests that psychedelic tryptamines can induce hallucinogenic and therapeutic effects through activation of the same receptor. It highlights the need for full mechanistic understanding of how these molecules produce therapeutic effects.

Kelmendi, B., Mandell, B., Olmstead, S. J., Pittenger, C., Stogniew, M., Warner-Schmidt, J.

This rat study finds that methylone (5-3-mg/kg) showed a reduction of 95% in immobility in the forced swim test (FST), a measure of antidepressant effects commonly used in mice studies. Methylone is similar to MDMA but shows less activity in the serotonin system. Pretreatment with an antidepressant (fluoxetine) didn't change the effects, indicating they may be co-administrated.

Gross, R., Lev-Ran, S., Rabinowitz, J.

This re-analysis of NSDUH survey data (n=56.000, 6.300 psychedelic users) finds that those who used LSD and psilocybin were more likely to have a substance dependency or abuse, those who used mescaline less likely, both compared to the rest of the survey group. As always, these are mere correlations and non-pharmacological (e.g. socio-economic) factors could explain both the positive and negative correlations.

Al Kindy, A., deVries, F. E., Doyle, Z., Hannon, B., Li, M., Mak, E., McIntyre, R. S., Patel, Z., Rodin, G., Rosenblat, J. D., Schulz-Quach, C., Zimmermann, C.

This open-label study (n=20) finds that ketamine (intranasal, 3x, 50-150mg) reduced depression in patients with cancer who were receiving palliative care. On day eight (one day after the last dose), the response and remission rates were 70% and 45%, respectively. The effects were partially sustained in the second week.

Carhart-Harris, R. L., Forstmann, M., Gandy, S., Irvine, A., Kettner, H., Luke, D., Sagioglou, C.

This secondary of survey data (n=3817) finds that nature-relatedness (NR) is only predicted by past use of psilocybin. As the surveys are observations, the question is still out if the pharmacology or the way people use different psychedelics (setting) is driving this result.

Alper, K., Cange, J., Sah, R., Schreiber-Gregory, D., Sershen, H., Vinod, K. Y.

This mice study found that psilocybin reduced alcohol consumption for three days, but this effect was only present in male mice.

Barrett, F. S., Davis, A. K., Griffiths, R. R., Gukasyan, N., Lancelotta, R., Nikolaidis, A.

This re-analysis of survey data (n=985) finds three different clusters (subtypes) of the psychedelic experience. The subtypes, found with machine learning, were associated with reduced anxiety and depression symptoms and other markers of psychological well-being. The subtypes were also highly reproducible across multiple psychedelic substances.

Jäncke, L., Jungwirth, J., Nowak, A., Nowak, P., Preller, K. H., Rieser, N. M., Schindowski, E. M., Schuldt, A., Seifritz, E., van Rotz, R., Vollenweider, F. X., Zahoranszky, K.

This double-blind placebo-controlled study (n=56) found that one psilocybin-assisted therapy (16mg/70kg, 2 prep + 3 integration meetings) session significantly reduced depressive symptoms (MADRS & BDI) in those suffering from a major depressive disorder (MDD, n=26). Fourteen days after the intervention, 54% of those in the psilocybin group met remission criteria (<10 on MADRS).

Carhart-Harris, R. L., Chandaria, S., Erritzoe, D., Friston, K. J., Gazzaley, A., Girn, M., Kettner, H., Mediano, P. A. M., Nutt, D. J., Rosas, F. E., Roseman, L., Timmermann, C., Weiss, B., Zeifman, R. J.

This theory-building paper (2022) introduces a new model of psychopathology called canalization, which is a form of plasticity that relates to increased model precision. It suggests that TEMP, combined with psychological support, can counter the entrenchment of canalization in pathological phenotypes, and offers suggestions for experiments to test its main hypotheses and implications.

Anand, A., Barnett, B. S., Dewey, E. N., Weleff, J.

This pre-print analysis of population survey data (2015-2019; 280.000 respondents) finds an increase in LSD use (from .06% to 0.9%, +47%). Those who self-reported Hallucinogen Persisting Perception Disorder (HPPD) didn't increase their use. LSD does not appear to contribute significantly to the country’s public health problems.

Carter, S. E., Gray, J. C., Johnson, M. W., Maples-Keller, J. L., Murphy, M., Roy, M. J., Wolfgang, A. S.

This interview study (n=21) presented service members and veterans, who had a history of traumatic brain injury (TBI) with information on psychedelic-assisted therapy (PAT). Before presenting info, they were neutral, after they had significantly more positive views on psychedelic drugs (3.2 out of 5), interest in PAT (3.7), and would support medical PAT (4.3).

Timmermann, C., Vollenweider, F. X.

This review (2022) proposes a unified neurophenomenological (NP) approach to studying non-ordinary states of consciousness (psychedelics, meditation, hypnosis). By focusing on the experience (phenomenology; e.g. interviews) and combining it with neurophysiological measures, a rich explanatory framework could emerge.

Gu, L-M., Ning, Y-P., Tan, J., Wang, C-Y., Yang, X-H., Zheng, W., Zhou, Y-L.

This study (n=135) finds that ketamine (6x 35mg/70kg) was just as effective for those experiencing melancholic (n=30) as non-melancholic depression.

Azmoodeh, K., Kamboj, S. K., Thomas, E.

This survey study (n=1315) of psychedelic users finds that a majority (67%) also meditated and nearly 40% combined both. From written accounts (n=256), six themes were identified, including compatibility between states, enhancement of experiences, positive changes in relating to the world, negative effects, meditation as a preparatory tool, and contextual considerations. Findings suggest meditation techniques could facilitate combining psychedelics, enabling lower, therapeutically important doses.

Cao, B., Ceban, F., Di Vincenzo, J. D., Ho, R., Jawad, M. Y., Meshkat, S., Rhee, T. G., Rosenblat, J. D., Teopiz, K. M.

This review (n=4,912) explores the evidence on blood-based and neuroimaging biomarkers underlying the antidepressant effects of ketamine. Ketamine can elicit an anti-inflammatorry effect, decrease at least one pro-inflammatory marker and data indicates the antidepressant effect is related to changes in synaptic plasticity and functional connectivity.

Castro-Rodrigues, P., Figueiredo, I., Marguilho, M.

This theory-building paper (2022) proposes that the antidepressant effects observed after ketamine infusions are mainly driven by its acute modulation of reward circuits and sub-acute increase in neuroplasticity, while its dissociative and psychedelic properties are driven by dose- and context-dependent disruption of large-scale functional networks.

Aru, J., Kristjan, K., Laukkonen, R., Tulver, K.

This pre-print review (2022) explores insight, showing that insight is a core component in psychotherapy and meditation, a key process underlying the emergence of delusions in schizophrenia, and a factor in the therapeutic effects of psychedelics as well as being commonly studied in problem solving literature.

Borentain, S., Drevets, W. C., Singh, J. B., Turkoz, I., Wajs, E., Williamson, D. E.

This study analysed data from a Phase III trial where ketamine plus an antidepressant were administered to patients with treatment-resistant depression (TRD) to investigate the relationship between dissociation and psychotic symptoms. Dissociation was reported as an adverse event in 14.3% (109/764) of patients, and Clinician-Administered Dissociative States Scale (CADSS) scores generally increased with every but with substantial variability.

Alves, C. L., Ciba, M., Cury, R. G., Pineda, A. M., Rodrigues, F. A., Roster, K., Thielemann, C.

This article (2022) used an EEG dataset from a study involving ayahuasca to investigate the ability of machine learning and complex network measurements to detect changes in brain activity automatically. After applying machine learning at three different levels of data abstraction, machine learning proved to be consistent with the current literature. It showed the highest accuracy in detecting the correlation of the EEG time series.

Bechand, B., Bock, H. A., Bonniwell, E. M., Calkins, M. M., Cao, A. B., Chandra, S. S., Cunningham, M. J., Duggan, P., Hwu, C., Katritch, V., Khirsariya, P., Lankri, D., McCorvy, J. D., Nazarova, A. L., Sames, D., Serrano, I. C., Vidyadhara, D. J.

This review (2022) provides a summary of the in-cell, in-animal and available clinical data with the non-hallucinogenic phenylalkylamine analogue Ariadne, and proposes a hypothesis for its lack of hallucinogenic effects and the therapeutic potential of this compound.

Castle, D., Feusner, J. D., Husain, M. I., Ledwos, N., Rodas, J. D.

This review (2022) evaluates the potential use of psychedelics in treating body dysmorphic disorder and other eating disorders.

Ashtari, A., DellaCrosse, M., Michalak, E. E., Morton, E., Pleet, M. M., Sakai, K., Woolley, J. D.

This follow-up study (n=15) used interviews to better understand self-reported psilocybin use among participants with bipolar disorder. Three overarching themes were identified: Mental Health Improvements, Undesired Mental Health Impacts and Salient Contextual Factors for psilocybin use.

Ashtari, A., Michalak, E. E., Morton, E., Pleet, M. M., Sakai, K., Woolley, J. D.

This survey study (n=541) assessed the risk and benefits of using psilocybin in people with bipolar disorder. 32.2% of participants had new/increasing symptoms after psilocybin trips, prominently manic symptoms, difficulties sleeping and anxiety. However, most participants reported that psilocybin was more helpful than harmful.

Chau, E. H., Di Vincenzo, J. D., Fancy, F., Gill, H., Husain, M. I., McIntyre, R. S., Mckenzie, A., Phan, L., Rodrigues, N. B., Rosenblat, J. D., Sethi, A., Tabassum, A.

This real-world study (n=66) assessed the effects of four sub-anaesthetic doses of intravenous ketamine (35-52.5 mg/70kg) in participants with bipolar depression. Significant antidepressant effects were measured using the QIDS-SR, and further reductions were observed following each subsequent infusion. The rate of remission was 20% after all infusions.

Becker, A. M., Duthaler, U., Holze, F., Kolaczynska, K. E., Liechti, M. E.

This study analysed data from three clinical trials (n=79) to characterize the pharmacokinetic-pharmacodynamic relationship of orally administered psilocybin (15-30 mg). Maximal psilocin concentrations were 11 ng/ml, 17 ng/ml, and 21 ng/ml after the administration of 15, 25, and 30 mg psilocybin, respectively, and maximal levels were reached after an average of 2 hours. The duration and intensity of subjective effects were dose-dependent.

Bannerman, D., Breant, B., Mengual, J. P., Sharp, T., Vyazovskiy, V. V.

This pre-print mice study finds that 5-MeO-DMT delayed the onset of REM sleep as measured with EEG, and showed behavioural signals (e.g. head twitches) consistent with psychedelic effects, whilst during the waking stage the EEG measures were also showing signs of REM sleep (paradoxical wakefulness).

Agrawal, M., Ameli, R., Berger, A., Shnayder, S., Sinaii, N.

This pre-print open-label trial (n=30) assessed psycho-spiritual change in cancer patients with major depressive disorder after a single dose of psilocybin (25mg). Participants underwent individual and group preparation and integration sessions, while the NIH-HEALS was used to assess psycho-spiritual change. Across all three factors (Connection, Reflection and Introspection) of the NIH-HEALS, psilocybin led to positive changes at all time points.

Karlawish, J., Largent, E. A., Lynch, H. F., Peterson, A., Sisti, D.

This review (2022) investigates six ethical issues concerning psychedelic medicine and research involving persons living with Alzheimer's Disease (AD)/ADRD, including autonomy, consent, ego dissolution, caregiving, exploitation of patient desperation, and methods to mitigate inequity.

Atoian, A., Atoian, S., Bowles, H., Bowles, N., Gerhke, S., Thangathurai, D.

This open-label at-home study (n=25) of ketamine tablets (37.5mg) finds that repeated 'micro' doses led to improvements in anxiety, stress, PTSD, and depression in 90-100% of participants.

Desai, S., Du, W., Jain, V., Xavier, S.

This analysis of survey data (n=125k, 8.4% psychedelic users) of US adolescents finds psychedelic users more likely to feel sad or hopeless, suicidal, and have higher use of other substances (alcohol, cigarette, ecstasy, etc.). Over the period of the survey (2001-2019), fewer adolescents were using psychedelics (from 13-7%).

Bohn, A., Kiggen, M. H. H., Ramaekers, J. G., Uthaug, M. V., van Oorsouw, K., Van Schie, H. T.

This open-label ceremonial use study (n=42) investigates the consciousness altering effects of San Pedro, a mescaline containing cactus, in ceremonial psychedelic retreats in Europe. Results indicate that San Pedro induces deviations from normal waking consciousness on all 11 subscales of the 11D-ASC, moderate scores of ego-dissolution, and a complete mystical experience in two thirds of participants.

Ambert, K. H., Buzzelli, V., Carbone, E., Feo, A., Hausman, M., Manduca, A., Perederiy, J. V., Schiavi, S., Trezza, V.

This rat model of Fragile X syndrome (FXS, genetic cause of autism -; ASD) finds that microdoses of psilocybin normalise cognitive performance in an object recognition test.

Belser, A. B., Ching, T. H., DePalmer, G., Kelmendi, B., Kichuk, S. A., Maloney, G., Pittenger, C.

This pre-print case study (2022) explores the effects of single-dose psilocybin in an individual with OCD. Treatment led to improvements in OCD symptoms and positive changes to the individuals' emotions, social and work function, and quality of life.

Achtyes, E. D., Ahearn, E., Frye, M. A., Goes, F. S., Greden, J., Lapidos, A., Lopez-Vives, D., Parikh, S. V., Senic, I., Sera, C. E., Vande Voort, J. L., Vest, E.

This qualitative study (n=21) uses interviews to characterize participants' experiences of intravenous (IV) ketamine infusions for treatment-resistant depression. 43% of participants had experienced remission. Five of the non-remitters were characterized as having experienced partial recovery based on their subjective experience.

Brown, P. J., Butters, M. A., Ciarleglio, A., Fadahunsi, N., Farber, N. B., Flint, A. J., Gebara, M. A., Karp, J. F., Lavretsky, H., Lenze, E. J., Mulsant, B. H., Oughli, H. M., Reynolds, C. F., Roose, S. P., Yang, L.

This open-label study (n=25) explored the effects of using intravenous ketamine to treat treatment-resistant depression (TRD) in participants over the age of 60. Depressive symptoms improved significantly, 48% of participants responded, and during the acute phase, executive function measures and the fluid cognition composite score improved (Cohen's d = 0.61).

Guss, J., Kraehenmann, R., Passie, T.

This review (2022) makes the case for lower dose (75-125μg) LSD with multiple sessions (5-8x) in combination with talk therapy. 15 years of use in Europe in the 1960s is explored to define the features of psycholytic therapy.

Deol, J. K., Lo, L. A., MacCallum, C. A., Pistawka, C. A.

This review (2022) aims to provide healthcare professionals with an overview of practical considerations for psilocybin therapy, focusing on patient safety.

Fava, M., Feeney, A., Hock, R. S., Iosifescu, D. V., Iovieno, N., Jha, M. K., Mathew, S. J., Murrough, J. W., Papakostas, G. I.

This meta-analysis (s=8, n=1437) compared the effect of intranasal esketamine to placebo (both in combination with standard antidepressants) as a treatment for major depressive disorder (MDD). It was found that intranasal esketamine, in combination with the standard treatment, did effectively reduce depression severity when compared to the placebo, with higher doses having a longer-lasting effect.

Alcázar-Córcoles, M. A., Bouso, J. C., Dos Santos, R. G., Hallak, J. E., Kohek, M., Ona, G., Rodríguez-Cano, B. J.

This interview study (n=13) explores the subjective experience of those seeking out ibogaine treatment for addictions. The themes focus on psychological effects such as transpersonal experiences, autobiographical memories, and personal insights.

Chambers, R., Goldberg, S. B., Hendricks, P. S., Osika, W., Simonsson, O.

This survey study (n=613) found that lifetime classic psychedelic use was modestly associated with more healthy tobacco-related and diet-related behaviours and a healthier BMI. Greater psychological insight was also modestly associated with health behaviour, diet- & exercise-related improvements.

Davis, A. K., Lancelotta, R., Ortiz Bernal, A. M., Raison, C. L.

This survey study (n=513) finds that reactivations (flashbacks) are common (27-86%) with 5-MeO-DMT use. The reactivations were generally perceived as positive (73-86%), with only some (4-7%) reporting them as negative. The change of reactivations was higher for those using 5-MeO-DMT in a structured setting, female, and older at the time of first use.

Carhart-Harris, R. L., Kaelen, M., Nutt, D. J., Roseman, L., Wall, M.

This re-analysis (n=15) of a trial with psilocybin (25mg) for depression (TRD) finds that music-evoked emotions are increased after treatment. The finding correlates with decreased anhedonia (inability to feel pleasure). fMRI measures also show a decrease in connectivity (FC) between the nucleus accumbens (NAc, music-related area) and the default mode network (DMN).

Breeksema, J. J., Kamphuis, J., Kuin, B., Niemeijer, A. R., Schimmel, N., Schoevers, R. A., van den Brink, W., Veraart, J. K. E., Vermetten, E.

This interview study (n=17) of those treated with esketamine (oral, 12x 35-70mg/70kg) finds that patients were often overwhelmed, lacked preparation, or couldn't let go of control. The authors suggest that more support (prep, during, after) can help patients 'let go' and achieve better outcomes.

Ferrari, S., Galeazzi, G. M., Galli, G., Magarini, F. M., Marchi, M., Micheli, E., Mordenti, F., Pingani, L., Travascio, A., Uberti, D.

This meta-analysis (n=1,298) explored the effects ketamine has on cognition, anxiety, quality of life, and social functioning in adults with psychiatric disorders. Ketamine was found to have positive effects on depression, anxiety and social functioning but not with respect to cognition and quality of life.

Aarde, S. M., Cozzi, N. V., D’Souza, D. C., Flynn, L. T., Gottschalk, C. H., Lindsey, H., Luddy, C., Pittman, B. P., Schindler, E. A. D., Sewell, R. A., Zhu, Y.

This double-blind placebo-controlled study (n=14) finds that psilocybin (10mg/70kg, 3x) reduced the frequency of cluster headaches by 3 (from a baseline of 10), but this effect was not significant. The intensity of the acute experience didn't impact the outcome. A study with more participants might find a significant treatment effect.

Costines, C., Derdiyok, E., Dinkelacker, J., Prugger, J., Schmidt, T. T.

This paper (2022) presents the development of the Altered State Database (ASDB). The ASDB was developed through a systematic literature review of psychometric questionnaire data on subjective experiences of altered states of consciousness (ASC). The ASDB allows for the calculation of comparable psychometric values of ASC experiences and of dose-response relationships of substances inducing ASC.