Blossom Pulse Archive
What happened in psychedelic research in 2022
523 events from 2022, dated by when they happened rather than when we logged them. Papers as they published, trials starting and finishing, programme milestones, and the news coverage around them, grouped by week.
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Week of 26 December 2022
Double-blind parallel RCT of single IV ketamine vs active midazolam control, with dPFC volumetric MRI as primary outcome (J Affect Disord 2023 Aug; Li WC, Chen LF, Su TP, Li CT, Lin WC et al.; Taipei Veterans General Hospital, Taiwan; PMID 37178823). n=48 randomised; participants: TRD (failed ≥2 adequate antidepressant trials) with active suicidal ideation; unipolar MDD. Intervention: single IV infusion of ketamine 0.5 mg/kg over 40 min vs midazolam 0.045 mg/kg active control. MRI-based dorsolateral/dorsal prefrontal cortex (dPFC/DLPFC) volumetric analysis at baseline and follow-up. MADRS, suicidal ideation scales as secondary outcomes. No CT.gov registration; no registration number reported in methods. CT.gov reverse-lookup (PMID, and author+condition search): 0 hits.
KetamineOpen-label, long-term extension Phase III safety study (n≈1148) of esketamine nasal spray (flexible 28–84 mg dosing) in participants with treatment-resistant depression, induction twice weekly for 4 weeks then individualised maintenance.
EsketamineThis double-blind, placebo-controlled trial (n=54) will administer 5-MeO-DMT intramuscularly in varying doses (single 0.5–13 mg and multiple-dose combinations) in healthy adults to assess pharmacokinetics, safety, and tolerability.
5-MeO-DMTAnalysing NSDUH data from 2015–2019, the authors found a 47% increase in past‑year LSD use (0.59% to 0.87%) without a proportional rise in hallucinogen use disorder. Use was linked to greater access and lower perceived risk plus specific sociodemographic and behavioural correlates (e.g. Asian race, low income, fewer children, history of selling drugs, past‑year suicide attempt in adults) and rose among pregnant, 26–34‑year‑old, married respondents and lifetime methamphetamine users, suggesting growing societal acceptance though LSD remains uncommon and not a major driver of public‑health harm.
LSDSuicidalityAdolescentsOpioid Use Disorder (OUD)Palliative & End-of-Life DistressPublic Health, Prevention & Behaviour ChangeSubstance Use Disorders (SUD)Depressive DisordersAnxiety Disorders
Week of 19 December 2022
In a pilot sample of 21 service members and veterans with traumatic brain injury, brief psychoeducation significantly increased positive attitudes and interest in psychedelic-assisted therapy (PAT), and most participants supported PAT availability in medical settings if proven beneficial. Participants nonetheless expressed health concerns (long-term effects, losing their mind, personality changes) and logistical barriers (time, transport, cost), indicating the need for targeted education, command support and practical facilitation to ensure access if PAT is approved.
MDMAPsilocybinDepressive DisordersPTSDVeteransMajor Depressive Disorder (MDD)Traumatic Brain Injury (TBI)Neurological InjuryRandomised, double‑blind, placebo‑controlled Phase I/II two‑part study (n=66 actual) of IV SPL026 (DMT fumarate): single‑dose, dose‑escalation in healthy volunteers; patients with MDD receive dose 1 randomised vs placebo and an open‑label second dose 2 weeks later.
DMTDouble-blind, placebo-controlled, randomised single-dose cohorts (n=64 across cohorts A–G) and an open-label multiple-dose cohort (J) investigating safety and serum pharmacokinetics of IV GH002 (5‑MeO‑DMT) in healthy volunteers.
5-MeO-DMTIn 135 patients given six 0.5 mg/kg intravenous ketamine infusions, both melancholic (n = 30) and non‑melancholic (n = 105) depression groups showed improvement in anhedonia with no significant difference in response or remission rates. Although melancholic patients had significantly lower MADRS anhedonia subscale scores at day 26, overall antianhedonic efficacy was similar between the groups.
KetamineDepressive DisordersRandomised crossover Phase I healthy volunteer study (n=8) assessing two oral DMT–harmala formulations with dose escalation (1.0→1.4 mg/kg DMT; 4→5.6 mg/kg harmala).
Ayahuasca
Week of 12 December 2022
The paper presents a unified multi-level model in which ketamine’s rapid antidepressant effects stem from acute modulation of reward circuits and a sub-acute increase in neuroplasticity, while its dissociative versus psychedelic phenomenology reflects dose- and context-dependent desegregation/disintegration of the salience network (SN) and default-mode network (DMN), respectively. Computationally, SN nodes are framed as priors about the ‘minimal’ self and DMN nodes as priors about the ‘biographical’ self, and the authors argue that relaxing high-level priors during psychedelic-assisted psychotherapy, aided by neuroplasticity, may permit revision of pathological self-models and boost long-term benefit.
KetamineDepressive DisordersNeuroimaging & Brain MeasuresMicrodosingThis open-label interventional trial (n=12) explored the feasibility of offering psilocybin therapy in a group setting to patients with cancer. The study aimed to decrease the therapist-to-subject ratio, implementing a 1:1 ratio with a group size of six patients.
PsilocybinThis 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.
SchizophreniaCreativityUsing EEG from ayahuasca experiments, the authors applied machine learning at three abstraction levels—raw signals, inter‑electrode correlations and complex‑network measures—and showed automatic detection of ayahuasca‑induced changes with highest accuracy from connectivity features (92%), then raw (88%) and network measures (83%). They report frontal and temporal activation, a novel F3–PO4 connection potentially linked to face‑like visual processing, and identify closeness centrality, assortativity and new community measures (suggesting larger communities and slower information dissemination) as key biomarkers possibly related to therapeutic mechanisms.
AyahuascaNeuroimaging & Brain MeasuresDepressive DisordersNeurocognitive DisordersIn patients with treatment‑resistant depression given a first dose of esketamine, dissociation was reported in 14.3% and CADSS item scores generally increased with investigator‑reported dissociation severity but showed substantial variability. No CADSS cutoff reliably discriminated presence versus absence of investigator‑reported dissociation, and psychotic symptoms were uncommon.
EsketamineKetamineDepressive DisordersTreatment-Resistant Depression (TRD)SchizophreniaSafety & Risk ManagementThis 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.
Older AdultsSchizophreniaNeurocognitive DisordersMedicinal Chemistry & Drug DevelopmentThis review (2022) evaluates the potential use of psychedelics in treating body dysmorphic disorder and other eating disorders.
Eating DisordersAn international web-based survey of 541 people with self-reported bipolar disorder who had used psilocybin found that about one-third experienced new or worsened symptoms (notably mania, sleep disturbance and anxiety), while emergency medical attendance was uncommon and participants overall rated psilocybin as more helpful than harmful. The authors conclude these subjective benefits warrant clinical trials in bipolar disorder but emphasise trials must include careful monitoring because bipolar symptoms may emerge or intensify after use.
PsilocybinAnxiety DisordersBipolar DisorderDepressive DisordersSafety & Risk ManagementThis qualitative follow-up of 15 adults with bipolar disorder who self-reported using psilocybin mushrooms found mixed effects: notable improvements in depressive symptoms, emotional processing, perspective-taking and sleep/relaxation, alongside risks including sleep disruption, increased mania, hospitalisation and distressing sensory experiences. Contextual factors (dose, polysubstance use, solo versus social use, pre-use sleep deprivation) influenced outcomes, and the authors conclude that carefully designed clinical trials are needed to evaluate safety and preliminary efficacy.
PsilocybinBipolar DisorderDepressive DisordersSubstance Use Disorders (SUD)SuicidalitySafety & Risk ManagementOpen-label Phase I interventional study (n=24 planned; registry reports 18 actual) testing single IV doses of SPL026 (DMT fumarate) in MDD patients on SSRIs versus those not on SSRIs to assess safety and tolerability.
DMTThis single-arm trial (n=15) aims to assess the safety, tolerability, and feasibility of using psilocybin (25mg) in combination with psychotherapy for methamphetamine use disorder.
PsilocybinOpen-label Phase I study (n=24 planned; 18 enrolled) single 27.5 mg IV SPL026 (DMT fumarate) 10-minute infusion in adults with major depressive disorder, comparing patients on stable SSRI versus those not on pharmacotherapy; primary outcomes: safety, PK/PD and exploratory efficacy.
DMTRandomised, double-blind, crossover neuroimaging study (n=67) comparing single doses of psilocybin 2 mg and 5 mg versus placebo in adults with and without Autism Spectrum Disorder to probe serotonin system regulation.
PsilocybinThis 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.
PsilocybinMajor Depressive Disorder (MDD)Depressive DisordersAnxiety DisordersHeadache Disorders (Cluster & Migraine)Healthy VolunteersMedicinal Chemistry & Drug DevelopmentChronic Pain
Week of 5 December 2022
This observational trial (n=13) was conducted by the University Hospital, Strasbourg, France. The study aimed to assess the tolerance and potential synergistic effect of combining intranasal esketamine with non-selective MAOIs in patients with depression and anxiety disorders.
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).
5-MeO-DMTDepressive DisordersNeuroimaging & Brain MeasuresThe open-label, single-arm study will initially take place at Numinus’ Vancouver clinic, with possible expansion to other locations. It will use EnfiniTea, a whole Psilocybe mushroom tea developed by Numinus Bioscience, to assess safety and support therapists’ training in psilocybin-assisted therapy. The findings may inform expanded access through Canada’s Special Access Programme.
PsilocybinThis 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.
KetamineDepressive DisordersPTSDAnxiety DisordersThis 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.
Neurocognitive DisordersEquity and EthicsOpen-label, single-group proof-of-concept study (n=15 actual) assessing simultaneous administration of oral aspirin (486 mg) + oral ketamine (80 mg) as an adjunct to oral antidepressant therapy in outpatients with treatment-resistant depression.
KetaminePhase I open-label randomized, two-period crossover PK study (n=14) comparing oral MDMA 100 mg under fed versus fasted conditions in healthy volunteers to assess food effects on bioavailability and safety.
MDMAThis 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.
PsilocybinAdolescentsAutism Spectrum Disorder (ASD)Analysing nationally representative YRBSS data from 2001–2019 (125,550 students), 8.4% of adolescents reported lifetime hallucinogen use, declining from 13.3% to 7.0% over the period. Hallucinogen users had significantly higher odds of feeling sad or hopeless, suicidal ideation and planning, and markedly greater co‑occurring use of alcohol, tobacco, cannabis and other illicit drugs.
LSDMDMAMescalineSuicidalityAdolescentsDepressive DisordersAnxiety DisordersObsessive-Compulsive Disorder (OCD)Opioid Use Disorder (OUD)Substance Use Disorders (SUD)Palliative & End-of-Life DistressPublic Health, Prevention & Behaviour ChangeThis 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.
MescalineAnxiety DisordersSet & Setting
Week of 28 November 2022
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).
KetamineOlder AdultsTreatment-Resistant Depression (TRD)Depressive DisordersSuicidalityNeurocognitive DisordersSafety & Risk ManagementThis 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.
LSDRandomised, double-blind, active-placebo-controlled Phase II trial (n=60) of two-session LSD-assisted psychotherapy (100 µg → 100/200 µg) versus low-dose LSD (25 µg ×2) for Major Depressive Disorder.
LSDThis 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.
IbogaineSubstance Use Disorders (SUD)This review (2022) aims to provide healthcare professionals with an overview of practical considerations for psilocybin therapy, focusing on patient safety.
PsilocybinTreatment-Resistant Depression (TRD)Depressive DisordersPalliative & End-of-Life DistressSafety & Risk ManagementMedicinal Chemistry & Drug DevelopmentAnxiety DisordersThis 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.
PsilocybinObsessive-Compulsive Disorder (OCD)Major Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersSuicidalityThis case study (n=1) describes how a teenager self-treated their psychosis (accompanied by complex PTSD and suicidal ideations) through high-dose LSD and low-dose DMT sessions. The hypothesis argues that psychedelics were able to break down the defensive system and allow for the integration of traumatic memories.
LSDPTSDSchizophreniaAdolescentsTreatment-Resistant Depression (TRD)Depressive DisordersAnxiety DisordersSuicidalityMicrodosingSafety & Risk ManagementPersonality DisordersPublic Health, Prevention & Behaviour ChangeThis first open-label real-world study (n=116) of esketamine (Spravato, up to 84mg, multiple dosings) finds similar positive outcomes as previous clinical trials. At three months, the response rate (64%) and remission (41%) for those with treatment-resistant depression are impressive. Only 3% of participants dropped out of the study because of side effects.
EsketamineKetamineDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)SuicidalitySafety & Risk ManagementThis 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.
KetamineEsketamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersThis 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).
PsilocybinAnxiety DisordersTobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Set & SettingEquity and EthicsThis open-label study (n=15) assessed the association between resting-state time-varying functional connectivity (tvFC) characteristics and plasma psilocin level (PPL) and subjective drug intensity (SDI) before and right after psilocybin intake (21mg/70kg). Findings suggest that the effects induced by psilocybin may stem from drug-level-associated decreases in the occurrence and duration of lateral and medial frontoparietal connectivity motifs.
PsilocybinDepressive DisordersNeuroimaging & Brain MeasuresHealthy VolunteersThis systematic review and meta-analysis of six trials (n = 340) found that electroconvulsive therapy (ECT) was superior to ketamine for acute reduction in depressive symptoms (pooled SMD −0.69), with no significant differences in cognition/memory or serious adverse events. Both treatments had distinct adverse‑effect profiles and the evidence was limited by low–moderate methodological quality and underpowered studies, so treatment should be individualised.
KetamineDepressive DisordersSuicidalityMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Chronic PainHeadache Disorders (Cluster & Migraine)Safety & Risk ManagementThis economic analysis (2022) finds that esketamine nasal spray (Spravato) is not cost-effective as compared to intravenous (racemic) ketamine for patients with treatment-resistant depression. The analysis uses quality-adjusted life years (QALYs), a common measure of added good years, and finds that esketamine and ketamine both add about two QALYs, but that the costs of the former are disproportionally higher.
EsketamineKetamineDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)SuicidalityHealth Economics & ReimbursementThis double-blind, placebo-controlled study (n=154) of ketamine (35mg/70kg) (or placebo) with (and without) positive self-regard training (automated self-association training) finds that the combination can extend the positive antidepressant (MADRS) effects of ketamine, whilst the effects of ketamine alone was not distinguishable from placebo 30 days later.
KetamineDepressive DisordersAdolescentsIn a US-representative sample (N = 2,822), lifetime use of classic psychedelics was associated with healthier tobacco- and diet-related behaviours, and among users greater psychological insight during their most insightful psychedelic experience predicted healthier exercise habits, healthier BMI and better diet (with some alcohol-related improvements). Although causality cannot be inferred, the results suggest psychological insight from classic psychedelic experiences may facilitate positive health-behaviour change, particularly for weight management.
Substance Use Disorders (SUD)Public Health, Prevention & Behaviour ChangeNuminus Wellness reported Q4 2022 revenue of C$4.2 million and gross profit of C$1.3 million, with gross margin rising to 31.5%. The company completed its acquisition of Novamind on 10 June 2022, adding US wellness clinics and Cedar Clinical Research, and ended the quarter with C$33.0 million in cash.
In a survey of 513 non‑clinical 5‑MeO‑DMT users, reactivations were more likely among women, older initiates, those with higher education and those dosing in structured group settings. Higher mystical experience scores, greater wellbeing and prior non‑drug non‑dual experiences predicted neutral or positive valence, suggesting reactivations are often benign or beneficial in this sample, though further work is needed to identify predictors of negative outcomes.
5-MeO-DMTDepressive DisordersAnxiety DisordersOpen-label, randomized crossover/wait-list study (n=30) testing two psilocybin sessions (20 mg, then 30 mg if tolerated) for treatment of OCD.
Psilocybin
Week of 21 November 2022
In patients with treatment-resistant depression, two-dose psilocybin therapy increased music-evoked pleasure that correlated with reductions in anhedonia and produced a post‑treatment decrease in nucleus accumbens functional connectivity with default mode network‑like regions during music listening, suggesting a neural mechanism for enhanced musical reward.
PsilocybinDepressive DisordersNeuroimaging & Brain MeasuresTreatment-Resistant Depression (TRD)Set & SettingThis qualitative IPA study of 17 patients with treatment‑resistant depression found that the key determinant of esketamine session experience and subsequent outcomes was patients’ ability to “let go” of control during overwhelming psychoactive effects, which was strongly shaped by preparation, emotional/physical support, and the treatment setting. The authors recommend better pre‑session education, optimised settings and targeted training for nurses/support staff to facilitate surrender and improve quality of care.
EsketamineKetamineAnxiety DisordersDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Set & SettingThis 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.
KetamineDepressive DisordersAnxiety DisordersSuicidalityThis 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.
In a first controlled human study, oral methylone (50–200 mg) showed rapid, dose‑proportional (linear) pharmacokinetics with Cmax and AUC increasing proportionally, Tmax ≈1.5–2 h and t1/2 ≈6–7 h. A validated LC–MS/MS assay quantified methylone, MDMA and metabolites and found the primary metabolite HMMC had much lower exposure (Cmax ~10–14× and AUC ~21–29× lower) and faster kinetics than the parent drug.
MDMAMedicinal Chemistry & Drug DevelopmentAn exploratory randomised, double‑blind, placebo‑controlled trial of a patient‑informed low‑dose psilocybin pulse regimen for cluster headache found no statistically significant reduction in attack frequency overall, although a moderate overall effect size (d = 0.69) and a large, sustained effect in chronic patients (d = 1.25) were observed. Psilocybin was well tolerated, therapeutic effects did not correlate with acute psychotropic intensity, and the authors conclude larger definitive trials are warranted.
PsilocybinChronic PainHeadache Disorders (Cluster & Migraine)Safety & Risk ManagementThe final participant in MAPP2, the second Phase 3 trial of MDMA-assisted therapy for post-traumatic stress disorder, was treated on 17 November 2022. The data will contribute to MAPS PBC’s planned 2023 new drug application, with results expected in the New Year.
MDMAPTSDIn a within‑subjects intravenous LSD versus placebo study using computational reinforcement‑learning modelling, LSD increased reward (and to a lesser extent punishment) learning rates and reduced stimulus stickiness, producing greater exploration while leaving simple win‑stay/lose‑shift measures unchanged. These effects indicate heightened plasticity that could facilitate the revision of maladaptive associations in clinical psychedelic therapy.
LSDHealthy VolunteersRandomised, parallel-group Phase II study (n=21 actual) testing intranasal ketamine (60 mg) twice weekly for 4 weeks versus saline placebo in patients with co-occurring opioid use disorder on buprenorphine and treatment-resistant major depressive disorder.
Ketamine
Week of 14 November 2022
This double-blind, placebo-controlled trial (n=1, terminated) aimed to determine whether perioperative ketamine (bolus 1 mg/kg + infusion 0.20 mg/kg/hr) increases postoperative pain tolerance and reduces opioid consumption in opioid-dependent patients undergoing spinal laminectomy/fusion.
KetamineThe final participant visit was completed in the multi-site study on 17 November 2022, with top-line results expected in the first quarter of 2023 and an FDA New Drug Application anticipated in the third quarter. MAPP2 included more than 50% participants of colour and expanded eligibility beyond MAPP1 to include moderate as well as severe PTSD.
MDMAPTSDPilot dosing, single-arm Phase 1 study (n=8 actual) evaluating single 25 mg psilocybin combined with repeated IV midazolam boluses to determine a midazolam regimen that permits a psychedelic experience while inducing amnesia for it in healthy volunteers.
PsilocybinComparative randomised, open-label, parallel-group trial (n≈403) of ECT (3×/week, up to 9 sessions) versus ketamine infusion (0.5 mg/kg IV, 2×/week, up to 6 sessions) for treatment-resistant depression with patient-reported outcomes as primary measures.
KetamineThis prospective, randomised, open-label trial (n=5) compared the analgesic efficacy and safety of a proprietary oral aspirin+ketamine formulation (AOK; ketamine 0.85 mg/kg + aspirin 324 mg) to Nurtec (rimegepant 75 mg ODT) in adult ED patients with acute headache.
KetamineA global survey of 10,836 ayahuasca users reported high rates of acute physical effects (69.9%, chiefly vomiting) and medium-term psychological effects (55.9%), though most users framed psychological effects as part of a positive integration process and only small proportions required medical (2.3%) or professional (≈12%) help. Risk factors for physical adverse effects included older age at first use, physical health conditions, greater use, prior substance use disorder and unsupervised settings, while mental health effects were linked to anxiety disorders, physical conditions and stronger spiritual experiences but were less common in religious contexts, suggesting targets for screening, support and policy.
AyahuascaAnxiety DisordersSubstance Use Disorders (SUD)Public Health, Prevention & Behaviour ChangeThe present study is a modern randomized cross-over trial, investigating different continuous intravenous DMT dose rates over a broad dose range.
DMTNon-randomised, sequential Phase I inhaled DMT study (n=27) in healthy volunteers; two ascending inhaled doses given in fixed order on the same day, 2 hours apart.
DMTThis review (2022) offers food for thought on the potential use of psychedelic-assisted therapy for treating eating disorders, particularly anorexia nervosa, using up-to-date research.
Major Depressive Disorder (MDD)Depressive DisordersPTSDObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Eating DisordersPooled analysis of three therapeutic trials using a fixed 25 mg psilocybin dose found that BMI did not predict acute psychedelic intensity, mystical experiences, perceptual changes, emotional breakthroughs, or two‑week improvements in well‑being, with Bayesian evidence supporting the null. These results support the use of a standardised fixed therapeutic dose rather than routine weight‑adjusted dosing.
PsilocybinEating Disorders
Week of 7 November 2022
GH Research held $256.9 million in cash at 30 September 2022 and reported a quarterly net loss of $0.4 million. It submitted European applications for an approximately 80-patient Phase 2b trial of inhaled 5-MeO-DMT candidate GH001 in treatment-resistant depression, expected to start in the first quarter of 2023, and initiated Phase 2a studies in bipolar II disorder and postpartum depression.
5-MeO-DMTDMTDepressive DisordersTreatment-Resistant Depression (TRD)This double-blind, randomized, placebo-controlled trial (n=93) aimed to assess the safety and efficacy of IV ketamine (PCN-101) in treating Treatment-Resistant Depression (TRD).
KetamineThis pre-print (2022) reviews the current body of evidence surrounding the effects psychedelics have on low-level sensory dimensions of experience, and corresponding brain dynamics, particularly visual dimensions. It is proposed that psychedelic-induced alterations in low-level sensory dimensions of experience are not entirely causally reducible to alterations in high-level dimensions, but rather co-occur in a dialogical interplay and play a causally relevant role in determining high-level alterations and therapeutic outcomes.
Neuroimaging & Brain MeasuresThe Massachusetts-based biotechnology company said the financing, led by Santé Ventures with several co-investors, will support platform development, SENS-01 and team growth. Sensorium plans to begin IND-enabling studies in 2023 and enter clinical trials by early 2024, targeting anxiety and depression.
Early Phase I, randomized, triple-blind, placebo-controlled trial (n=250 MDD; +60 healthy controls) testing a single sub‑anesthetic IV ketamine infusion (0.5 mg/kg) versus saline to assess glutamate stress response, anhedonia, decision-making, and emotion processing.
KetamineIn a randomized, double-blind, placebo-controlled crossover study in 24 healthy subjects, a single 40 mg oral dose of the 5‑HT2A antagonist ketanserin given one hour after 100 µg LSD rapidly reversed the acute psychedelic response—shortening subjective effect duration from 8.5 to 3.5 hours and attenuating visual/auditory alterations, ego dissolution, cardiovascular effects and mydriasis—without altering LSD pharmacokinetics or BDNF elevations. These findings support that LSD’s acute effects depend on 5‑HT2A receptor occupancy and indicate ketanserin can serve as a planned or rescue agent to shorten or mitigate LSD experiences in research and therapy.
LSDHealthy VolunteersMedicinal Chemistry & Drug DevelopmentThis perspective (2022) provides an understanding of the psychedelic experience through 1) ego dissolution and mystical states, 2) hyperassociative states, and 3) the role of set and setting.
Set & SettingMedicinal Chemistry & Drug Development
Week of 31 October 2022
This retrospective analysis (n=171) examined the effectiveness of esketamine in participants with treatment-resistant depression (TRD). A significant reduction in depressive symptoms was observed using the PHQ-9 and GAD-7 from baseline to last the last treatment.
KetamineEsketamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersAnxiety DisordersSuicidalitySafety & Risk ManagementPublic Health, Prevention & Behaviour ChangeThis primate study (n=12) found that ayahuasca (at 3 points in time) led to better resilience to being separated from the family groups. The animals that had received ayahuasca (n=6) showed no indication of anhedonia (inability to feel pleasure) and showed higher cortisol reactivity (positive).
AyahuascaMajor Depressive Disorder (MDD)Depressive DisordersPublic Health, Prevention & Behaviour ChangeThis double-blind active-placebo controlled trial (n=233) tested the effect of a single dose of psilocybin (25/10/1mg) with supportive therapy for treatment-resistant depression. The primary endpoint at three weeks finds a significant reduction in depressive symptoms (MADRS, 12-point drop from baseline of 32) that was significantly greater in the 25mg group vs the 1mg (placebo) group (6.6 points larger drop). The response (>50% drop in MADRS score) in the 25mg group dropped from 37% at 3 weeks to 20% at 12 weeks.
PsilocybinAnxiety DisordersDepressive DisordersTreatment-Resistant Depression (TRD)Headache Disorders (Cluster & Migraine)SuicidalitySafety & Risk ManagementChronic PainIn an exploratory analysis of 32 participants from a Phase 2 open‑label trial of manualised MDMA‑assisted therapy for PTSD, 84% reported chronic pain and 75% reported pain‑related disability. MDMA‑AT was associated with significant reductions in pain intensity, disability and overall Chronic Pain Grade Scale severity in the high‑pain subgroup and reduced pain intensity in the medium‑pain subgroup, supporting further investigation of MDMA‑AT for comorbid chronic pain.
MDMAChronic PainPTSDOpen-label pilot study (n=12) of a single oral 25 mg dose of psilocybin for adults with treatment-resistant body dysmorphic disorder with follow-up over 3 months.
PsilocybinThis randomised, double-blind, placebo-controlled Phase III study (n=121) compares three sessions of MDMA-assisted psychotherapy (initial 80–120 mg with supplemental half-dose 40–60 mg) versus placebo with identical therapy in adults with moderate PTSD.
MDMAOpen-label, single-group Phase I study (n≈11) assessing safety, feasibility, and acceptability of a single 25 mg oral psilocybin dose with supportive psychotherapy and multidisciplinary palliative care in cancer survivors with demoralization and chronic pain.
PsilocybinThis observational, naturalistic study (n=1000), conducted by the Psychedelic Data Society (with the Quantified Citizen app), is set to explore the relationship between substance use and personality profiles.
Using regression dynamic causal modelling of resting-state fMRI in a randomized placebo-controlled crossover (n=45), LSD produced widespread increases in interregional effective connectivity and reduced self-inhibition — except in occipital regions where interregional connectivity decreased and self-inhibition increased — consistent with a perturbation of the brain's excitation/inhibition balance. Both effective connectivity and functional connectivity distinguished LSD from placebo with high accuracy (EC 91.11%, FC 85.56%), indicating their promise as clinically relevant biomarkers.
LSDNeuroimaging & Brain MeasuresThis analysis of neuroimaging (M/EEG) compares data from patients with schizophrenia (n=29) and healthy volunteers under the influence of LSD (75μg, n=17) or ketamine (n=19). It finds that although both show increased neural signal diversity, only for those with schizophrenia did it increase the precision (weighting) of sensory information. Both groups increase 'bottom-up' signalling, but of a different kind.
LSDKetamineSchizophreniaNeuroimaging & Brain MeasuresHealthy VolunteersThis systematic review (n=46; s=6) examined the efficacy and safety of ketamine for the treatment of pediatric depression (mean age=15.7 y/o). Findings suggested that ketamine, administered intravenously at doses ranging from 35mg/70kg to 140-490mg/70kg, significantly reduced depressive symptoms without severe adverse events.
KetamineAdolescentsOlder AdultsMajor Depressive Disorder (MDD)Depressive DisordersSafety & Risk ManagementThis review (2022) highlights the potential of arketamine (the 'right-handed' part of ketamine) as an antidepressant. Though studies less than ketamine (or esketamine, the 'left-handed' part), arketamine potentially has fewer side effects and more potent antidepressant effects.
KetamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Bipolar DisorderDepressive DisordersPTSDSuicidalitySafety & Risk ManagementThis survey study (n=66) explored the effects of naturalistic psychedelic use on recalled psychological distress and trauma symptoms among Indigenous peoples living in the United States and Canada who had experienced racial trauma. The most commonly used psychedelics were psilocybin, MDMA and LSD. Participants recalled experiencing fewer symptoms of depression, anxiety, stress, trauma, symptoms of discrimination, and alcohol use in the 30 days after (vs. before) the psychedelic experience
PsilocybinMDMALSDDepressive DisordersPTSDAnxiety DisordersEquity and EthicsImplementation & Service DeliveryThis Phase I open-label trial (n=14) studied the safety of psilocybin when administered to healthy participants enrolled in a psychedelic-assisted therapy training programme. Participants ingested 25 mg of psilocybin extract, and vital signs, including heart rate, blood pressure, temperature, and ECG, were monitored.
Psilocybin
Week of 24 October 2022
The aim of the present study is to evaluate the safety, tolerability and efficacy of increasing doses of ibogaine in 12 alcoholic patients.
IbogaineSingle-group mechanistic feasibility study (n=19) administering up to 10 mg psilocybin (COMP360) on two occasions to people with OCD to assess cognitive inflexibility, neuroplasticity, and symptom changes.
PsilocybinPhase I/II, randomized, triple-blind, placebo-controlled ascending-dose IV study (Part 1, HVs) and Phase IIa open-label IV study in MDD (Part 2); single IV doses of ELE-101 (psilocybin) with PK/PD and safety assessment.
PsilocybinUsing MRI data from 22 ayahuasca users and 22 matched controls, the study found preliminary evidence of greater corpus callosum thickness in users—most notably in the isthmus—and a positive association between callosal thickness and number of past ayahuasca sessions in the rostral body, although these effects did not survive corrections for multiple comparisons. These results suggest possible links between ayahuasca use and callosal structure but require replication in larger, ideally longitudinal, samples before clinical conclusions can be drawn.
AyahuascaNeurocognitive DisordersNeuroimaging & Brain MeasuresImmunology & InflammationPublic Health, Prevention & Behaviour ChangeIn a naturalistic longitudinal study of 53 ayahuasca‑naïve attendees, a single facilitated ceremony produced broad 1‑month improvements in depression, anxiety, stress, substance use, personality traits, relationships and spirituality. Baseline characteristics—particularly high negative emotionality and body dissociation and low self‑efficacy—predicted greater benefit while facets of the mystical experience did not, indicating potential for personalised treatment and warranting randomised controlled trials.
AyahuascaAnxiety DisordersDepressive DisordersSubstance Use Disorders (SUD)Personality & Trait FactorsPublic Health, Prevention & Behaviour ChangeSingle-group interventional study (n=48) assessing effects of personal psychedelic experience (MDMA, LSD, psilocybin) on therapists' therapeutic attitude and related capacities during SÄPT training.
MDMALSDPsilocybinThis review (2022) makes the cases for using MDMA-assisted therapy (MDMA-AT) in the treatment of borderline personality disorder (BPD). The authors draw parallels between using MDMA-AT to treat disorders similar to BPD, such as PTSD, and provide considerations for designing future clinical trials.
MDMAPTSDEating DisordersSuicidalityBorderline Personality Disorder (BPD)Personality DisordersThis double-blind placebo-controlled study (n=18) explored the effects of two microdoses of LSD (13 & 26μg) on reward processing using a monetary incentive delay task. LSD increased three reward-related ERP components, reflecting increased hedonic, motivational, and affective processing of feedback, indicating that LSD increases reward-related activity in humans.
LSDDepressive DisordersAnxiety DisordersNeuroimaging & Brain MeasuresHealthy VolunteersMicrodosingEligible projects may involve psychedelic or non-psychedelic 5-HT2A agonists, ketamine or MDMA. The opportunity is open to small businesses or collaborators developing these compounds as therapies for substance use disorders.
MDMAKetamineRandomised, double-blind, two-period crossover Phase I study (n=24) testing whether 6-week paroxetine pretreatment reduces 5-HT2A receptor expression and subjective response to a single 0.1 mg oral LSD dose in healthy volunteers.
LSDPhase I open-label randomised two-way crossover PK study in healthy volunteers (n=14) comparing 25 mg COMP360 as a single 25 mg capsule versus five 5 mg capsules in the fed state.
PsilocybinThis comprehensive review (2022) explains the neural basis of how psychedelics work. It covers serotonin receptors, changes in structural plasticity, and the long-term effects of psychedelics. The discussion covers the future of psychedelics, including non-hallucinogenic compounds.
Neuroimaging & Brain MeasuresEquity and EthicsMedicinal Chemistry & Drug DevelopmentIn an open‑label pilot of 16 medically hospitalised recent suicide attempters, a single intravenous ketamine infusion (0.5 mg/kg) produced rapid, large reductions in suicidality and depression at 24 hours and 5 days (Cohen’s d 1.7–8.8) that were sustained up to six months. The study indicates ketamine is a feasible, rapidly acting intervention for acute suicidality in real‑world Consultation‑Liaison settings.
KetamineDepressive DisordersSuicidalityPublic Health, Prevention & Behaviour Change
Week of 17 October 2022
This systematic review shows that classical psychedelics (LSD, psilocybin, ayahuasca) consistently cause acute disruption of resting-state connectivity within the Default Mode Network and increase cross-network functional connectivity, but it remains unclear how central DMN modulation is to their therapeutic effects. The article synthesises existing evidence and highlights gaps to guide future mechanistic research.
AyahuascaLSDPsilocybinAnxiety DisordersDepressive DisordersObsessive-Compulsive Disorder (OCD)PTSDSchizophreniaNeurocognitive DisordersNeuroimaging & Brain MeasuresOpen-label observational study (n=36) collecting EEG and genetic data from patients with treatment-resistant MDD receiving intramuscular ketamine as standard of care.
KetamineThis rapid scoping review maps a wide range of drug-specific, behavioural and peer-related harm-reduction strategies used by ecstasy (MDMA) users in recreational settings and shows users obtain guidance from diverse sources including friends, clubs and user-oriented websites. It also finds many user-facing websites lack evidence citations and that adherence to strategies varies with users' goals and experience, indicating a need for more effective, evidence-informed communication.
MDMAPalliative & End-of-Life DistressSafety & Risk ManagementPublic Health, Prevention & Behaviour ChangeDepressive DisordersAnxiety DisordersPhase I, randomised double‑blind placebo‑controlled single‑dose PK study (n=44) with an integrated open‑label food‑effect crossover (25 mg) assessing safety, tolerability, PK and QTcF of COMP360 (psilocybin) in healthy volunteers.
PsilocybinUsing data from 83 sources, this review outlines recommendations for current practice in preparatory sessions in substance-assisted psychotherapy (SAPT), providing information on safety measures and screening procedures, preparation of set and setting, session contents, methods, and roles, prerequisites, and appropriate conduct of therapists.
Set & SettingThis post hoc analysis of two Phase III double-blind studies assessed the effects of baseline irritability on clinical outcomes in participants with treatment-resistant depression (TRD) (n=560) treated with intranasal ketamine (esketamine) plus an oral antidepressant (ESK + AD). ESK + AD improved symptoms of depression regardless of baseline irritability level and increased odds of achieving a response in all participants.
KetamineEsketamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersAnxiety DisordersSuicidalitySafety & Risk ManagementA placebo-controlled self-blinding trial (n=240) found that the probability of correctly guessing a microdose decreased with the number of prior microdoses (β = −.017±.007; p = .009), indicating tolerance development; this effect was significant for LSD/LSD-analogues (β = −.026±.007; p < .001) but not for psilocybin (β = .013±.014; p = .36), suggesting microdosers may need dosing breaks and that psilocybin could be better suited for long-term use.
LSDPsilocybinMicrodosingCreativityObservational long-term follow-up (n=24) of participants from PSIL201 (psilocybin or niacin) using web surveys and telephone interviews over 24 months.
PsilocybinRandomized, parallel-group study (n=154 actual) testing intravenous subanesthetic ketamine with or without adjunctive computer-based cognitive training for treatment-resistant depression; mechanistic outcomes (fMRI, IAT, cognitive flexibility) and clinical outcomes (MADRS acute; QIDS over 12-month follow-up).
KetamineThis review (2022) uses data from three randomised-controlled trials (RCTs), eight open-label trials and 30 case series to explore the efficacy, safety and tolerability of using ketamine in the treatment of depression. Ketamine was found to have sustained antidepressant effects when administered intravenously, intranasally, orally and possibly intramuscularly and was found to be well-tolerated.
KetamineTreatment-Resistant Depression (TRD)Depressive DisordersSubstance Use Disorders (SUD)Neurocognitive Disorders
Week of 10 October 2022
This review (2022) explores mescaline's pharmacological and behavioural effects using preclinical and clinical research. The pharmacological mechanisms of mescaline are similar to those of other classical psychedelics i.e. binding at the 5HT2A receptor. Mescaline can improve well-being and mental health conditions, particularly alcohol use disorder.
MescalineAnxiety DisordersAlcohol Use Disorder (AUD)Neuroimaging & Brain MeasuresInterpersonal Functioning & Social ConnectednessSubstance Use Disorders (SUD)Single-blind, randomised Phase II trial (n=6, terminated) comparing Almond Therapy plus intranasal esketamine to Treatment as Usual plus intranasal esketamine over 28 days; esketamine given twice-weekly for 8 doses (56 mg initial, then 56 or 84 mg).
EsketamineThis interventional trial (n=100) aims to investigate the long-term maintenance effects of ketamine and esketamine on reducing suicide risk in patients with Major Depressive Disorder (MDD) and suicidal ideation (SI).
KetamineEsketamineThe programme comprises two pivotal trials and one long-term follow-up study. COMP 005 will compare a single 25mg dose with placebo in 378 participants, while COMP 006 will assess repeat 25mg, 10mg and 1mg doses in 568 participants, with MADRS change at Week 6 as the primary endpoint.
PsilocybinDepressive DisordersTreatment-Resistant Depression (TRD)Randomised, parallel-group Phase II study (n=32 actual) comparing COMP360 psilocybin 25 mg versus 1 mg with psychological support in adults with anorexia nervosa to evaluate efficacy and safety.
PsilocybinRandomised, double-blind Phase I study (n=60) evaluating single oral doses of KUR-101 versus placebo and oxycodone in healthy adults to assess safety, PK/PD, analgesic and respiratory effects.
The paper proposes that MDMA facilitates extinction of traumatic memories in PTSD by increasing BDNF availability in fear‑memory circuits, thereby enhancing synaptic plasticity for relearning and extinction. It argues this molecular action, together with MDMA’s pro‑social effects that strengthen the therapeutic alliance, explains the clinical benefits of MDMA‑assisted therapy.
MDMAPsilocybinAnxiety DisordersPTSDSuicidalityUsing NSDUH data (2008–2019; N = 484,732), the authors found that race and ethnicity significantly moderate the associations between lifetime MDMA and psilocybin use and past‑month psychological distress and past‑year suicidality. MDMA and psilocybin were linked to reduced odds of distress and suicidality among White participants, but showed far fewer protective associations for racial and ethnic minority groups, highlighting the need for more research on identity-related moderators.
MDMAPsilocybinSuicidalityAdolescentsEquity and Ethics
Week of 3 October 2022
This meta-analysis (s=6) explored the therapeutic effects of psilocybin, LSD and ayahuasca on depressive symptoms in the clinical setting. When administered with psychological support, all psychedelics led to significant reductions in depressive symptoms at all measured timepoints (1-day, 1-week, 3-5 weeks, and 6-8 weeks). Some limitations include the small sample sizes used in most individual studies and the use of a cross-over design for long-term follow-up, which made it difficult to include those results in the meta-analysis.
PsilocybinLSDAyahuascaMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersAnxiety DisordersHeadache Disorders (Cluster & Migraine)Palliative & End-of-Life DistressInterpersonal Functioning & Social ConnectednessChronic PainThis open-label single-group assignment trial (n=20) aims to evaluate the feasibility, tolerability, and preliminary effectiveness of MDMA-assisted therapy for adjustment disorder (AD) in 10 dyads of cancer patients and their concerned significant others (CSOs).
MDMANuminus Bioscience developed the tea bag using validated Psilocybe cubensis strains, with a phase 1 trial planned for practitioners receiving experiential training in psilocybin-assisted therapy, including research with Cedar Clinical Research. Numinus also submitted the product to Health Canada for inclusion on the psilocybin supplier list for the Special Access Program.
PsilocybinIn healthy volunteers, a medium–high dose of psilocybin produced a significant increase in trait mindfulness at three months that correlated positively with the intensity of the acute mystical-type experience. Higher baseline trait mindfulness was also associated with lower 5‑HT2A receptor binding in the right amygdala.
PsilocybinAnxiety DisordersHealthy VolunteersNeuroimaging & Brain MeasuresThis double-blind placebo-controlled pilot study (n=20) conducted by the University of California, San Diego aims to investigate the safety and efficacy of psilocybin (25mg) in treating chronic phantom limb pain (PLP).
PsilocybinThe study design is a double-blind, randomized, active-control trial of adolescents (ages 13-18 years) with recent suicidal behaviors (suicide attempt or increased suicidal ideation). All participants will be treated through a suicide prevention IOP (typically 6-8 weeks), as well as clinically indicated psychosocial and/or psychopharmacological treatments. Ketamine/midazolam treatment will occur twice weekly during the first two weeks of the study, followed by weekly assessments through week 12.
KetamineThe present study aims to investigate the effect of psilocybin on treatment-resistant PTSD
PsilocybinThis observational trial (n=30) will investigate the neurocomputational model of ketamine treatment response predictions in treatment-resistant depression (TRD).
KetamineThis paper (2022) combines data of the brain’s resting state under the influence of LSD and cortical mapping of 5-HT2A receptors within the framework of network control theory to validate the central tenets of the REBUS model of psychedelics. In accordance with this model, LSD-induced flattening of the brain’s energy landscape, corresponding to greater flexibility for state transitions and more dwell time in brain states than encode bottom-up activity (e.g. salience network) and decreased persistence of states dominated by top-down (frontoparietal) activity.
LSDNeuroimaging & Brain MeasuresUsing US National Survey on Drug Use and Health data (2005–2018), the study found that lifetime MDMA (ecstasy) use was associated with lower risk of overweight/obesity and reduced odds of past-year heart condition/cancer, hypertension and diabetes, and with higher odds of reporting better overall health. These associations remained after adjustment for multiple confounders, though the authors note longitudinal studies and clinical trials are needed to test causality.
MDMAPTSDSubstance Use Disorders (SUD)Interpersonal Functioning & Social Connectedness
Week of 26 September 2022
Randomized, double-blind, comparator-controlled crossover trial (n=30) testing low-dose IV ketamine (0.5 mg/kg, 40 min infusion) versus midazolam in patients with OCD at the Medical University of Vienna.
KetamineThis crossover trial (n=24) investigates the acute effects of R- and S-MDMA compared to racemic MDMA and placebo in healthy subjects.
MDMAThis double-blind placebo-controlled study (n=25) assessed the effects of LSD on metabolic pathways associated with neural plasticity, to gain insight into the relationship between neural plasticity, ageing and LSD-induced cognitive gains in both humans and rodents. LSD treatment in humans (50μg) enhanced performance in a visuospatial memory task, and in a novel object recognition task in rodents indicating that LSD has nootropic effects.
LSDOlder AdultsHealthy VolunteersIn a double‑blind randomised clinical trial of adults with alcohol dependence receiving psychotherapy, two high‑dose psilocybin sessions reduced the percentage of heavy drinking days over 32 weeks to 9.7% versus 23.6% with active placebo (mean difference 13.9 percentage points; 95% CI 3.0–24.7; P = .01). Psilocybin was well tolerated with no serious adverse events, supporting further study of psilocybin‑assisted therapy for alcohol use disorder.
PsilocybinOlder AdultsAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)Safety & Risk ManagementUsing a novel turbulence framework that quantifies vorticity (local synchrony) and extends metastability to space and time, the study shows that LSD and psilocybin produce consistent yet discriminable compression of the brain’s functional hierarchy, most notably altering the default mode network. These results quantify how two psychedelics modulate hierarchical brain dynamics and support their proposed mechanistic role relevant to therapeutic applications.
LSDPsilocybinTreatment-Resistant Depression (TRD)Depressive DisordersSubstance Use Disorders (SUD)This open-label (real-world evidence) paper (n=1247) argues that at-home sublingual ketamine (tablets for under the tongue) is both safe (only four patients dropped out) and effective (remission of 32% for depression and anxiety). Patients only spoke with a 'guide' (not a therapist) over video as the study was conducted during Covid. The results look promising, though the study sponsor (Mindbloom) has come under scrutiny recently.
KetamineAnxiety DisordersDepressive DisordersSafety & Risk ManagementOpen-label, single-group Phase II study (n=15) of psilocybin-assisted psychotherapy for treatment-resistant depression: two 25 mg oral dosing sessions (6 weeks apart) with preparatory and integrative therapy over 12 weeks.
PsilocybinA retrospective study of at‑home, off‑label self‑administration of sublingual rapid‑dissolve ketamine tablets found the treatment to be safe, well tolerated and to produce significant reductions in PHQ‑9 and GAD‑7 scores in 47.6% of patients after three doses, with higher response rates following a six‑dose course. These results suggest sublingual ketamine is a feasible alternative to intravenous ketamine for treatment‑resistant depression and anxiety.
KetamineAnxiety DisordersDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Both classic (LSD, DOI) and dissociative (ketamine, PCP) psychedelics induced widespread hypersynchrony of high‑frequency oscillations (HFOs) across the cognitive‑limbic cortex‑basal ganglia system in freely moving rats, with strong phase locking and sub‑millisecond interregional delays, whereas firing‑rate changes were predominantly inhibitory and not specific to psychedelic drugs. This HFO hypersynchrony could disrupt cross‑system information integration and plausibly underlies psychedelic‑induced alterations in perception and cognition, highlighting a potential target for antipsychotic interventions.
LSDKetamineSchizophreniaThis chemistry paper (2022) simulates the docking of 75 million molecules (tetrahydropyridines, THP) on the serotonin 2a (5-HT2a) receptor. The initial screening led to 17 molecules that were further refined down to two molecules ((R)-69 & (R)-70). These two had antidepressant effects (in mice) but didn't show (acute) psychoactive activity (head-twitch response, change in movement).
Depressive DisordersMedicinal Chemistry & Drug DevelopmentEmpathBio, atai’s wholly owned subsidiary, will conduct a randomised, double-blind, placebo-controlled study of single-ascending oral doses of EMP-01, with Medsafe and HDEC approvals. The trial will assess safety, tolerability, behavioural measures, pharmacokinetics and the IDEA-1 app, informing future Phase 2 development for PTSD and other indications.
MDMAHealthy VolunteersPTSDDouble-blind, randomised clinical trial (n=45) comparing intraoperative ketamine infusion (0.5 mg/kg over 40 minutes) versus saline in patients with major depressive disorder undergoing non-cardiac surgery.
KetamineUsing data from 13 healthy volunteers given intravenous DMT, the authors developed a population PK/PD model (two‑compartment PK, high clearance ≈26 L/min, effect‑site sigmoid Emax with EC50 ≈95 nM) linking plasma concentrations to subjective psychedelic intensity. Simulations translate exposure into dose–response predictions (median maximum intensity ratings for 1–20 mg), providing a tool to guide dose selection in clinical investigations.
DMTHealthy VolunteersDepressive DisordersAnxiety DisordersMedicinal Chemistry & Drug DevelopmentIn an interpretative phenomenological analysis of participant narratives from a pilot phase 2 trial, MDMA-assisted therapy for anxiety related to life‑threatening illness was reported to facilitate processing of trauma and grief, evoke mystical/existential experiences and reduce physiological arousal, yielding improved coping, reduced psychological symptoms, greater vitality and a reconnection to life. These accounts suggest MDMA‑AT may bolster emotional resilience in the face of illness relapse, though trial limitations temper conclusions and indicate the need for further study.
MDMAAnxiety DisordersDepressive DisordersPTSDPalliative & End-of-Life Distress
Week of 19 September 2022
Usona Institute is exploring psilocybin’s therapeutic potential for major depressive disorder using clinical trials focused on safety and efficacy. It has also completed all dosing sessions in its first clinical study of 5-MeO-DMT in healthy volunteers, while developing supportive therapeutic frameworks for potential healthcare use.
5-MeO-DMTDMTPsilocybinDepressive DisordersMajor Depressive Disorder (MDD)Also covered by Usona Institute
This mixed-methods systematic review of 15 studies (n = 2,182) found that both ego-dissolution and connectedness predict improved outcomes after psychedelic experience, with ego-dissolution tending to trigger rapid but transient psychological change and connectedness being more sustained and linked to enduring positive therapeutic feelings. The authors suggest emphasising ego-dissolution during preparation and fostering connectedness during integration to refine models of psychedelic therapy.
Depressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Palliative & End-of-Life DistressSet & SettingMedicinal Chemistry & Drug DevelopmentThe one-to-two-year programme will train psychiatrists in patient screening, preparation, dosing, treatment settings and psychotherapy for psilocybin and other psychedelics. Each university will receive $300,000 over two years, with curricula based on the latest research.
PsilocybinThis review (2022) investigates the subjective (experiential) measures that are being used in psychedelic trials and finds good correlations between mystical experiences (MEQ) and oceanic boundlessness and therapeutic/mood outcomes. Similar results (with fewer participants studied) are also found for challenging experiences, psychological insight, and emotional breakthroughs. Alas, not much comment is made about the construct validity of the measures.
Major Depressive Disorder (MDD)Depressive DisordersAnxiety DisordersObsessive-Compulsive Disorder (OCD)Tobacco/Nicotine Use Disorder (TUD)Palliative & End-of-Life DistressSet & SettingSubstance Use Disorders (SUD)
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