Blossom Pulse Archive
What happened in psychedelic research in 2025
389 events from 2025, 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 29 December 2025
Feasibility, single-group psilocybin-assisted psychotherapy pilot (n≈15) delivering one 25 mg oral psilocybin session with preparatory and integration therapy for demoralization in hospice patients.
PsilocybinThis Phase I, randomised, double-blind, placebo-controlled sequential trial (n=48) studied single ascending doses of LPH-5 in healthy male participants aged 18 to 65 years. Six cohorts received one of six dose levels of LPH-5 or placebo, with the main aim of assessing safety and tolerability. The trial also evaluated LPH-5 pharmacokinetics over 48 hours and pharmacodynamic effects using subjective mood questionnaires and quantitative EEG. LPH-5 is represented in Blossom under the 2C-X compound family because 2C-B is the closest psychedelic in the current taxonomy.
2C-XThis open-label, non-randomised Phase IV pilot (n=20) evaluates the safety and feasibility of manualised 4-session CBT with three adjunctive subcutaneous ketamine doses (weekly, weeks 2–4) for adults with methamphetamine use disorder.
KetamineThis interventional trial (n=3) will assess the efficacy and safety of esketamine for the treatment of Rett Syndrome (RTT) in children aged 5 to 10 years.
EsketamineThis 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.
DMTNeuroimaging & Brain MeasuresIn an exploratory randomised, double‑blind trial in adults with frequent migraine, single or two‑dose psilocybin produced reductions in migraine frequency similar to an active diphenhydramine placebo and no serious adverse events were observed. Incomplete blinding and nonsignificant between‑group differences despite large effect sizes in psilocybin arms indicate the need for larger, better‑controlled trials with headache‑specialist input to separate drug and non‑drug effects.
PsilocybinHeadache Disorders (Cluster & Migraine)Chronic PainMicrodosingSafety & Risk ManagementPublic Health, Prevention & Behaviour Change
Week of 22 December 2025
This Phase II, randomised, open-label, non-inferiority trial (n=168) will evaluate the safety, tolerability and effectiveness of group-based MDMA-assisted therapy compared with individual MDMA-assisted therapy in adults (18–75 years) with PTSD diagnosed following the events of 7 October 2023. The primary outcomes are change in PTSD symptoms measured by CAPS-5 and PCL-5 from baseline to end-of-treatment (Week 17 in the group-based arm; Week 13 in the individual arm). Eligible participants will be randomised to either group-based MDMA-assisted therapy (groups of up to 7 participants with the same trauma type) or individual MDMA-assisted therapy; both arms include preparatory sessions, three MDMA dosing sessions and integration sessions. MDMA HCl is administered orally in a divided dose with a supplemental dose 1.5 to 2 hours after the initial dose: first dosing session 80 mg with 40 mg supplemental, second and third dosing sessions 120 mg with 60 mg supplemental. Dosing sessions include on-site monitoring of vital signs, overnight stay after sessions and safety assessments (physical exam, urine drug screen, ECG, laboratory tests), with adverse events and suicidality monitored (C-SSRS) and oversight by an external DSMB; estimated enrolment is 168, with study start 24 December 2025 and completion anticipated 31 March 2029.
MDMAThe $4.9 million study, led by STRONG STAR and Emory University, is examining MDMA-assisted Massed Prolonged Exposure Therapy for PTSD. MAPS provided four days of live online education plus 15 hours of asynchronous content for participating therapists and supervisors, funded by philanthropic partners including Mission Within Foundation.
MDMAPTSDThis placebo-controlled, randomised trial (n=90) investigates the efficacy of a single infusion of ketamine combined with magnesium sulphate in treating refractory chronic cluster headache (CCH).
KetamineRandomised, quadruple-masked Phase II trial (n=24) comparing single low (1 mg) vs high (25 mg) PEX010 psilocybin doses to study motivation/reward and cognitive flexibility circuits in people with opioid use disorder.
PsilocybinRandomised, double-blind, placebo-controlled Phase II trial (n=90) testing a single 25 mg dose of psilocybin plus psychological support versus placebo in treatment-seeking adults (20–70 yrs) with alcohol use disorder.
PsilocybinParticipants in a pilot study of psilocybin‑assisted psychotherapy for methamphetamine use disorder found the intervention acceptable and reported that confronting vividly challenging psychedelic experiences—described as “leaning into the obstacle”—fostered new self‑understandings and shifts in relationships that reduced the salience of methamphetamine. A strong therapeutic alliance, characterised by concentrated attention and intersubjective intimacy, was seen as critical to these positive changes.
PsilocybinTreatment-Resistant Depression (TRD)Depressive DisordersAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)
Week of 15 December 2025
This randomized, double‑blind trial (n=20) will assess the effects of a single oral dose of ayahuasca versus oral esketamine on the menstrual cycle and premenstrual symptoms in healthy women aged 18–65, with the primary outcome measured by the Premenstrual Symptom Tracking Instrument (PSST) from enrolment to three weeks. Participants will be allocated in a parallel design to an experimental arm receiving oral ayahuasca or an active comparator arm receiving oral esketamine under double‑blind conditions. The study is described as basic science, enrols healthy female volunteers without psychiatric or other medical comorbidities, has estimated enrolment of 20, and is scheduled to start on 20 December 2025 with completion anticipated in July 2026.
AyahuascaEsketamineThis Phase II, randomized, double‑blind, parallel trial (n=10) will evaluate the effects of a single oral dose of ayahuasca versus oral esketamine in adults with posttraumatic stress disorder (PTSD), with the primary outcome measured by the Posttraumatic Stress Disorder Checklist for DSM-5 from enrolment to the end of treatment at 3 weeks. Adults aged 18 to 65 years meeting criteria for PTSD will be randomised to one of two arms—experimental oral ayahuasca or active‑comparator oral esketamine—each administered as a single dose; participants with psychiatric or other medical comorbidities are excluded. The study is sponsored by the University of Sao Paulo, is due to start on 20 December 2025, and has an estimated completion in July 2026.
AyahuascaEsketamineThis randomised, double-blind, parallel trial (n=20) will study the effects of a single dose of oral ayahuasca or oral esketamine on body image perception in healthy female volunteers aged 18–65, with the primary outcome assessed using the Body Shape Questionnaire over a 3-week period. The study purpose is basic science investigation of acute effects on body perception. Participants will be randomised to one of two arms—oral ayahuasca (experimental) or oral esketamine (active comparator)—in a double-blind design; enrolment is limited to healthy women without psychiatric or other medical comorbidities. Body Shape Questionnaire scores will be collected from enrolment to the end of treatment at 3 weeks. The trial is sponsored by the University of Sao Paulo and is scheduled to run from December 2025 to July 2026.
AyahuascaEsketamineIn this retrospective study of 30 patients receiving LSD or psilocybin for treatment‑resistant depression or anxiety, LSD produced a delayed, sustained increase in heart rate peaking at 3–4 hours while psilocybin showed an earlier decline, with a significant time × substance interaction that persisted after adjusting for age and anxiety and no serious cardiovascular events observed. These preliminary findings suggest distinct temporal cardiovascular profiles for LSD versus psilocybin but should be interpreted cautiously given the retrospective design, small sample and dose imbalance.
LSDPsilocybinAnxiety DisordersDepressive DisordersTreatment-Resistant Depression (TRD)Healthy VolunteersSafety & Risk ManagementDouble-blind, adaptive, two-stage, multi-site, Phase II randomised trial (up to 480 consented to yield 240 randomized) comparing single moderate (20 mg) and high (30 mg) doses of oral psilocybin with low-dose (1 mg) control in OUD patients on methadone.
Psilocybin
Week of 8 December 2025
In a within-subject pharmacoimaging study of 11 healthy psychedelic-experienced volunteers, inhaled DMT acutely reduced connectivity between the left ventral tegmental area and the right nucleus accumbens while increasing connectivity between the nucleus accumbens and anterior cingulate cortex and between the medial prefrontal cortex and anterior cingulate. These connectivity shifts correlated with changes in volition and perception and suggest a potential therapeutic mechanism for disorders of reward processing.
DMTHealthy VolunteersDepressive DisordersObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Chronic PainNeuroimaging & Brain MeasuresThis Phase I, open-label, dose-escalation trial (n=10) will evaluate the safety and psychological effects of a combined psilocybin and D-Serine formulation; cohort 1 will receive psilocybin 15 mg with D-Serine 5 g, and if safe cohort 2 will receive psilocybin 25 mg with D-Serine 7 g.
PsilocybinThis double-blind, randomised, placebo-controlled, crossover mechanistic trial (n=52) tested single IV infusions of ketamine (0.71 mg/kg), midazolam (0.025 mg/kg), dexmedetomidine (0.025 mg/kg), or saline in non-treatment-seeking smokers.
KetaminePhase III, quadruple-blind, randomised, placebo-controlled trial (n=330) of CYB003 (8 mg and 16 mg; two dosing sessions ~3 weeks apart) as adjunctive treatment for major depressive disorder.
PsilocybinQualitative interviews with 12 participants from a randomized, placebo‑controlled single‑dose psilocybin trial for treatment‑refractory OCD showed that set and setting strongly shaped acute (often partial) perceptual, emotional and metacognitive experiences, which were followed by post‑dosing changes in OCD symptoms, perceptions and behavioural/metacognitive processes. These changes mapped onto putative mechanisms of ERP and ACT, suggesting hypotheses for further study and potential value in integrating psilocybin with structured psychotherapy for OCD.
PsilocybinObsessive-Compulsive Disorder (OCD)SchizophreniaSet & SettingPublic Health, Prevention & Behaviour ChangeIn an open‑label Phase IIa trial (n-12), a single 10 mg intranasal dose of 5‑MeO‑DMT (BPL‑003) given alongside a 10‑week relapse‑prevention CBT programme was acceptable in safety and tolerability in people with moderate–severe alcohol use disorder. Over 12 weeks, participants showed large improvements in drinking (mean abstinent days rose from 33.2% to 80.8% and heavy drinking days fell from 56.2% to 13.2%), providing preliminary evidence of efficacy and supporting larger controlled trials.
5-MeO-DMTAlcohol Use Disorder (AUD)Chronic PainSafety & Risk ManagementPublic Health, Prevention & Behaviour ChangeSubstance Use Disorders (SUD)In a retrospective analysis of 233 participants with treatment‑resistant depression given 1, 10 or 25 mg COMP360 psilocybin, dose was the strongest and most consistent predictor of the acute psychedelic experience, while pretreatment clinical characteristics made only modest, variable contributions (positive affect, lower generalized anxiety, higher executive function and greater personality‑disorder symptoms each influenced different experience dimensions). These results challenge the assumption that pretreatment traits are major determinants of the subjective psilocybin experience.
PsilocybinAnxiety DisordersDepressive DisordersTreatment-Resistant Depression (TRD)Set & SettingPersonality DisordersThis secondary analysis (n=52) describes a Phase I/II group psilocybin retreat model for people with metastatic cancer and moderate to severe anxiety or depression, using a secular ritual approach based on rites of passage. It describes a model designed for a 3-day in-person retreat and linked to safety and efficacy outcomes in the trial.
PsilocybinAnxiety DisordersDepressive DisordersPalliative & End-of-Life Distress
Week of 1 December 2025
The proposed policy would make one Phase 3 trial sufficient in most cases, although the FDA has not formally announced the change. Usona could seek approval based on a single 240-participant Phase 3 study, compared with Compass Pathways’ two-study programme involving more than 800 patients, while the bulletin also covers the Freedom to Heal Act and Compass’ planned Q1 readout.
PsilocybinA four-page comment in the Journal of Eating Disorders scrutinised a case report describing two patients who reportedly recovered dissociated traumatic memories during psilocybin treatment for anorexia nervosa. The authors said vivid memory-like experiences do not establish genuine memory recovery, and highlighted alternative explanations including suggestibility, framing and misinformation. They also cautioned against preparing patients for forgotten material to emerge.
PsilocybinEating DisordersIn an open‑label 8‑week pilot trial, thematic analysis of interviews with 17 people with major depressive disorder found that many participants reported enhanced self‑determination, increased connectedness, clearer cognitive processing and improved emotional well‑being that they linked to reduced depressive symptoms. However, responses were heterogeneous—some reported negative effects or no benefit—and the open‑label design without a placebo control limits causal conclusions and emphasises the need for careful dosing and realistic expectations.
LSDDepressive DisordersMicrodosingMajor Depressive Disorder (MDD)Anxiety DisordersHealthy VolunteersIn a double-blind, placebo-controlled trial of 50 volunteers, ayahuasca produced robust perceptual, emotional and mystical experiences alongside EEG changes (notably reduced global alpha and increased frontomedial delta and right-posterior theta/beta), with acute lower theta linked to stronger mystical effects and baseline theta and beta oscillations predicting interoceptive and emotional responses.
AyahuascaHealthy VolunteersNeuroimaging & Brain MeasuresPilot sequential study (n=44 planned; initial n=5 open-label pilot) assessing feasibility, acceptability, and safety of four twice-weekly IV ketamine infusions (0.5 mg/kg) followed by a brief narrative intervention versus minimally enhanced usual care in Veterans with chronic low back pain and depression.
KetamineThis Phase II, open-label trial (n=20) will evaluate the effects of a single administration of MM402, the R-enantiomer of MDMA, in adults aged 18 to 45 with Autism Spectrum Disorder (ASD). The primary aim is to assess changes in social responsiveness and communication deficits, as measured by an 11-point Numerical Rating Scale (NRS) at various time points post-dose. The study will include approximately twenty participants diagnosed with ASD who exhibit clinically significant deficits in socialisation and communication. Participants will receive a single dose of 200 mg MM402, with assessments occurring at baseline, pre-dose, and at 2, 4, 6, 8, and 24 hours post-dose, as well as on day 15. The trial will exclude individuals with certain eye movement abnormalities, a history of psychotic or bipolar disorders, current substance use disorders, or any clinically significant unstable illness. The study is sponsored by Definium Therapeutics US, Inc., with an estimated start date in December 2025 and completion anticipated by August 2027.
MDMAPhase I, non-randomised, sequential 3-session psilocybin-assisted psychotherapy study (n=30) using 3+3 dose-escalation sequences (doses 15→45 mg) to evaluate safety, tolerability, and preliminary efficacy for PTSD.
PsilocybinPhase 1, open-label, single-group study (n=150) assessing psychological effects and safety of a single 120 mg MDMA dose (optional 60 mg supplemental) paired with preparatory and integrative therapy sessions in healthy volunteers and therapists in training.
MDMAOpen-label, single-group Phase II study (n=10) assessing a single 25 mg oral dose of psilocybin for adults with MDD and co-occurring BPD to evaluate safety and efficacy.
PsilocybinThis phenomenological exploration trial (n=15) aims to investigate the transient dissociative state induced by esketamine in patients with depressive disorder.
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.
MDMAPsilocybinLSDDMTAyahuascaMescalineAnxiety DisordersDepressive DisordersOlder AdultsSafety & Risk ManagementThis qualitative sub-study (n=21) nested within a Phase II trial found that psilocybin treatment enabled participants with PTSD to engage with trauma-related material both directly and indirectly through affective, somatic, and self-transcendent experiences, contrasting with standard treatments that require direct confrontation with trauma memories.
PsilocybinPTSDDepressive DisordersThis secondary analysis (n=26) of adults with treatment-resistant depression from an open-label psilocybin-assisted psychotherapy trial found statistically significant improvements in processing speed and executive function at two weeks post-treatment, with gains on Trail Making Tests remaining significant after adjusting for depressive symptoms; however, reliable change indices showed that the proportion of participants achieving meaningful improvement (4.2–12.5%) did not exceed chance expectations, suggesting observed gains may reflect practice effects rather than genuine procognitive benefits.
PsilocybinDepressive DisordersTreatment-Resistant Depression (TRD)Bipolar DisorderNeurocognitive Disorders
Week of 24 November 2025
This Phase II, open-label, single-group trial (n=20) evaluated BMB-101 in adults with drug-resistant absence epilepsy, including epilepsy with eyelid myoclonia, or a developmental and epileptic encephalopathy such as Dravet or Lennox-Gastaut syndrome. All participants received oral BMB-101 liquid twice daily, with titration and treatment lasting up to 3 months within a study period of up to 6 months. The study assessed change in seizure frequency over 10 weeks in participants with developmental and epileptic encephalopathy and change in generalised spike-wave discharges on 24-hour EEG over 6 weeks in participants with absence epilepsy. Safety, tolerability and clinical response were monitored across six clinic visits.
2C-XRandomised, double-dummy, triple-blind, placebo-controlled, parallel groups trial (n=90) investigating sublingual LSD microdosing (2–20 µg, start 8 µg) twice weekly for 8 weeks versus active placebo (caffeine or methylphenidate) in people with MDD.
LSDDouble-blind, randomized, placebo-controlled Phase II outpatient trial (n=90) evaluating CLE-100 (oral esketamine) 1 tablet once daily adjunctive to standard antidepressant therapy for 4 weeks in adults with MDD and inadequate response to ≥2 antidepressants.
EsketamineThis double-blind trial (n=220) of adolescents with severe depression will modify electroconvulsive therapy with esketamine.
EsketamineDMT shifts brain oscillatory dynamics away from criticality—towards subcritical regimes—in alpha and adjacent (theta) bands, increasing entropy and reducing complexity. These shifts, quantified via a functional excitatory–inhibitory ratio, correlate with the intensity of subjective self‑dissolution.
Neuroimaging & Brain Measures
Week of 17 November 2025
Using individualised whole‑brain computational modelling fitted to fMRI and diffusion MRI, the authors simulated administration of LSD and psilocybin and applied in silico perturbations to compare states of consciousness and assess treatment effects in disorders of consciousness. Simulated psychedelics shifted patients' brain dynamics closer to criticality—especially in the minimally conscious state—with responses in UWS linked to structural connectivity and in MCS to baseline functional connectivity, providing a computational rationale for psychedelic therapies and personalised prediction.
LSDPsilocybinNeuroimaging & Brain MeasuresEquity and EthicsThis open-label study (n=9) found that an encapsulated DMT-harmala alkaloid product (pharmahuasca) produced dose-dependent mystical experiences that exceeded those reported in most previous ayahuasca studies and were associated with beneficial persisting psychological effects in healthy volunteers.
Depressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Healthy VolunteersThis interventional trial (n=0, withdrawn) aimed to investigate the brain activity effects of psychedelic medicines, specifically psilocybin or MDMA, in healthy volunteers.
PsilocybinMDMA
Week of 10 November 2025
Open-label single-group pilot (n=16 dyads, 8 PTSD+ veterans and their partners) testing MDMA-assisted bCBCT: 8-session therapy with two full-day MDMA sessions for PTSD+ veterans to evaluate preliminary effectiveness on PTSD and relationship functioning.
MDMAPhase II, double-blind, randomized, quadruple-masked RCT (n=72) testing four IV ketamine infusions (0.5–0.75 mg/kg over 40 minutes) versus midazolam (0.02–0.03 mg/kg) as adjunctive treatment for moderate to severe treatment-resistant bipolar depression.
KetamineThis preclinical rat study (n=24; 8 rats per group) shows that a single dose of psilocybin (1.0 mg/kg) or the selective 5-HT2A receptor agonist 25CN-NBOH (1.5 mg/kg) reduces immobility in the forced-swim test, with effects persisting for at least three months. Electrophysiology of medial prefrontal cortex (mPFC) Layer 5 neurons reveals long-lasting functional, but not structural, plasticity—characterised by changes in resting membrane potential, neuronal firing rates, and excitatory synaptic input. In contrast, dendritic spine density and gene-expression markers related to synaptic structure remain unchanged, indicating enduring functional alterations rather than persistent structural modifications.
Depressive DisordersIn a double-blind randomised trial of patients with long-standing moderate-to-severe depression, two doses of psilocybin plus placebo and six weeks of escitalopram produced comparable reductions in negative affective bias on a facial emotion recognition task at the six-week endpoint. Changes in bias were not associated with concurrent symptom change, although improved recognition of positive faces predicted symptom improvement at week 10 only in the escitalopram group, suggesting partially overlapping but distinct cognitive mechanisms.
PsilocybinDepressive DisordersThe open-label extension enrolled 107 of 126 eligible patients with treatment-resistant depression, who received 12 mg of BPL-003 eight weeks after an initial 0.3 mg, 8 mg or 12 mg dose. The company said core and extension findings support advancing the 8 mg dose into Phase 3, subject to discussions with the FDA.
Depressive DisordersTreatment-Resistant Depression (TRD)Using a no‑report MEG visual mismatch response paradigm, the study found that long‑term ayahuasca users report reduced fear of death and greater life satisfaction, but nonetheless retain intact neurophysiological markers of self‑specific death denial at automatic perceptual levels. The neural denial marker correlated with lower self‑reported death acceptance and reduced accessibility of death‑related thoughts, suggesting ayahuasca alters conceptual and affective engagement with death but not unconscious self‑specific denial.
AyahuascaPalliative & End-of-Life DistressDepressive DisordersAnxiety DisordersIn the first qualitative study embedded in a randomised, placebo‑controlled trial, interviews with 40 healthy males who microdosed 10 µg LSD every third day for six weeks identified effects across mood, social life, mindfulness, cognition/creativity and physiology, with overarching themes of increased openness and bidirectional (positive and negative) effects. These findings highlight clinically relevant signals (notably changes in anxiety) that bear on patient and dose selection for mood‑disorder trials and emphasise set, setting and placebo‑related uncertainty as key considerations for psychedelic trial design.
LSDAnxiety DisordersMicrodosingCreativitySet & SettingPersonality & Trait Factors
Week of 3 November 2025
The company said Germany granted the European Union’s first compassionate-use approval for psilocybin for treatment-resistant depression. It also announced PEX010 supply for two phase 2 trials with University College London and FDA authorisation for a University of Washington phase 2 trial in alcohol use disorder and post-traumatic stress disorder. Filament reported $337,082 in cash and cash equivalents and $268,522 in total revenue as of 30 September 2025.
PsilocybinDepressive DisordersPTSDGH Research said one hold topic remains in discussions with the FDA over GH001’s IND. In Phase 2b, GH001 reduced MADRS scores versus placebo by 15.5 points on Day 8, while 73% of participants were in remission at six months in the open-label extension. The company expects to start its global pivotal programme in 2026.
SuicidalityThis randomised, triple-blind, placebo-controlled crossover trial (n=18) will investigate the acute analgesic (anti-pain) effects of N,N-dimethyltryptamine (DMT) on experimentally induced acute nociceptive pain, hyperalgesia, and allodynia in healthy participants.
DMTKetamineThis Phase I double-blind placebo-controlled trial (n=32) using microphenomenology interviews found that intranasal 5-MeO-DMT produced dose-dependent subjective effects with rapid onset peaking at 8-15 minutes and return to baseline by 45-60 minutes, characterised by minimal visual effects but strong emotional and bodily experiences, including emotional breakthroughs and personal insights.
5-MeO-DMTSubstance Use Disorders (SUD)Healthy VolunteersCompass Pathways completed enrolment in the COMP006 Phase 3 trial with 585 participants and plans to disclose nine-week COMP006 and 26-week COMP005 data in Q1 2026. The company expects 26-week COMP006 data in early Q3 2026 and reported a positive September 2025 FDA meeting on potential rolling submission strategies for COMP360 in treatment-resistant depression.
PsilocybinIn an open‑label pilot where 10 hospice patients received a single 25 mg psilocybin‑assisted therapy session, the intervention was feasible and well tolerated with no serious psilocybin‑related adverse events and produced a significant reduction in demoralisation at three weeks (mean reduction 8.8 points, p=0.0196). Acceptability varied because of the intervention’s emotional intensity, indicating PAT can be integrated into hospice care but requires optimisation and larger controlled trials.
PsilocybinMajor Depressive Disorder (MDD)Depressive DisordersAnxiety DisordersPalliative & End-of-Life DistressSafety & Risk ManagementEquity and Ethics
Week of 27 October 2025
This combined 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).
PsilocybinMicrodosingCreativityOpen-label, randomised feasibility trial (n=24) comparing psilocybin microdosing alone versus microdosing plus meditation in healthy adults; four supervised microdoses over two weeks.
PsilocybinThis double-blind, randomised, placebo-controlled trial (n=40) will investigate the persisting effects of a single dose of psilocybin (1-30mg) on structural plasticity in healthy older adults.
PsilocybinThis Phase IV interventional trial (n=60) aims to investigate the effectiveness of intraoperative ketamine in reducing postoperative depressive symptoms in patients undergoing lumbo-peritoneal shunt insertion.
KetamineThis Phase I, randomised, open-label, crossover trial (n=85) will assess whether psilocybin’s anti-anhedonic effects in people with major depressive disorder and anhedonia are linked to the psychedelic experience. Participants will receive two oral 25 mg doses of psilocybin across two sessions, with 1 mg oral risperidone given 30 minutes before psilocybin in one session to blunt acute psychedelic effects. The study includes two experimental sequences: psilocybin first followed by psilocybin plus risperidone, or the reverse order. Participants will undergo three MRI sessions: baseline before treatment, then one day after each psilocybin session. The trial will compare clinical, behavioural and imaging responses using fMRI tasks related to aesthetic processing, reward, sexual arousal and cognitive flexibility, alongside self-report measures of well-being, depression, anhedonia and altered states of consciousness, with follow-up extending to about 12 weeks after enrolment.
PsilocybinThis 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.
PsilocybinDepressive DisordersMajor Depressive Disorder (MDD)Set & SettingEquity and EthicsThis 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.
PsilocybinDepressive DisordersVeteransAdolescentsMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)This open-label observational trial (n=20) will investigate the effects of intravenous ketamine on treatment-resistant bipolar depression, with an interventional component of functional magnetic resonance imaging (fMRI).
KetamineSix patients have been treated, including two at Johns Hopkins University School of Medicine and four at Yale School of Medicine’s Department of Psychiatry. The multicentre trial will assess CMND-100’s safety, tolerability and pharmacokinetic profile, while exploring preliminary effects on alcohol cravings and consumption. Two additional sites in Israel have also been activated.
The appointment is effective immediately, bringing more than 30 years of pharmaceutical research and development experience focused on neuroscience to Compass Pathways. Jonas will support the company’s development of COMP360, its investigational synthetic psilocybin treatment, while Lönngren’s board tenure ends after more than six years.
PsilocybinDepressive DisordersOpen-label pilot, single-arm Phase II study (n=10) evaluating safety and feasibility of an 8-week psilocybin-assisted psychotherapy intervention (25 mg plus optional 37.5 mg) to support opioid tapering in adults with chronic pain.
Psilocybin
Week of 20 October 2025
Single-group, single-blind Phase I interventional study (n=30) of psilocybin-assisted psychotherapy with three oral dosing sessions (1 mg then 25 mg ×2) given every two weeks in adults with treatment-resistant anorexia nervosa.
PsilocybinIn a multicentre phase 2b randomised placebo‑controlled trial of 198 adults with moderate to severe GAD, a single dose of MM120 (lysergide D‑tartrate) produced a dose‑dependent reduction in HAM‑A scores at 4 weeks, with 100 µg and 200 µg showing significant improvements versus placebo (least‑squares mean differences −5.0 and −6.0 points, respectively). Adverse events were dose‑related—most commonly visual perceptual changes and nausea—supporting the efficacy and informing dose selection for phase 3 trials.
LSDAnxiety DisordersDepressive DisordersOlder AdultsSubstance Use Disorders (SUD)Headache Disorders (Cluster & Migraine)Safety & Risk ManagementChronic Pain
Week of 13 October 2025
The study will recruit people recently detoxified from street opioids such as heroin, or replacement therapies including methadone and buprenorphine. Participants will receive psilocybin at Imperial’s NIHR Clinical Research Facility, with therapist support, brain scans and up to six months of follow-up assessing opioid use, cravings, mental health and well-being. The trial is funded by NIHR and the Government’s Office for Life Sciences.
PsilocybinThe designation applies to adults with treatment-resistant depression and follows Phase 2b results showing clinically meaningful, statistically significant symptom reductions within 24 hours of a single 8 mg or 12 mg dose, sustained through eight weeks. Phase 3 trials are expected to begin in the second quarter of 2026, subject to FDA alignment.
Depressive DisordersTreatment-Resistant Depression (TRD)In a randomized, placebo‑controlled ascending‑dose study in 48 healthy volunteers, single IV doses of GM‑2505 up to 20 mg were well tolerated and showed dose‑proportional pharmacokinetics (t1/2 40–50 min) with dose‑dependent neuroendocrine, neurophysiological and subjective psychedelic effects, including decreased theta/alpha and increased gamma EEG power. The duration of cardiovascular and subjective effects was intermediate between psilocybin and DMT, indicating a practical 10–15 mg IV dose range for supervised clinical use.
DMTPsilocybinDepressive DisordersHealthy VolunteersMajor Depressive Disorder (MDD)Neuroimaging & Brain MeasuresSafety & Risk ManagementMedicinal Chemistry & Drug DevelopmentOpen-label case series (n=25) assessing feasibility of Perinatal SMILES (interpersonal psychotherapy plus two subcutaneous ketamine doses ~24 h apart) to improve post-cesarean mood in low-income women.
KetamineThis 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.
PsilocybinDMTKetamineMedicinal Chemistry & Drug DevelopmentMajor Depressive Disorder (MDD)Depressive DisordersPTSDSubstance Use Disorders (SUD)Safety & Risk Management
Week of 6 October 2025
Triple-blind, randomised, parallel-group Phase II trial (n=36) testing a single 25 mg vs 1 mg PEX010 psilocybin dose (2:1) in individuals on MAT for opioid use disorder to assess neural and clinical outcomes including urine drug screens and MAT adherence.
PsilocybinPhase II randomised, quadruple-blind parallel trial (n=75 actual) of IV ketamine (0.5 mg/kg weekly ×3) vs active placebo (midazolam 0.045 mg/kg) combined with Prolonged Exposure therapy for Veterans with PTSD.
KetamineThis 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'.
MDMASubstance Use Disorders (SUD)Healthy Volunteers
Week of 29 September 2025
Aldworth and Ali had served as interim co-executive directors since April 2025, after Kris Lotlikar stepped down as executive director to become MAPS board secretary. Founder and president Rick Doblin will continue guiding research initiatives and international projects, while the new directors will lead MAPS’ research, drug policy, education and community work.
MDMAPTSDAlso covered by MAPS
An open‑label pilot trial of two 25 mg psilocybin sessions with preparatory and integration psychotherapy for treatment‑resistant depression produced a clinically meaningful reduction in self‑rated depressive symptoms at three weeks (Hedges’ g = −1.27) that was maintained at 20 weeks, although individual responses varied (two sustained responders, three relapses, two non‑responders). Exploratory analyses linked pre‑dosing mindset, spiritual experiences and perceptual shifts to outcome trajectories, with adverse events consistent with prior studies and no serious adverse events.
PsilocybinDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Healthy VolunteersSafety & Risk ManagementThis triple-blind, placebo-controlled trial (n=30) will investigate the effects of a sub-hallucinogenic dose of psilocybin (5 mg) combined with Imagery Re-Scripting (ImRS) on cognitive processes and self-harm behaviour in young people aged 16–25.
PsilocybinThis randomised, double-blind, low-dose comparator-controlled Phase IIb trial (n=87) will study the effects of different doses of psilocybin (PEX010; 1-10-25mg) delivered during a psilocybin-assisted psychotherapy (PAP) session in individuals with adjustment disorder following a cancer diagnosis.
PsilocybinThis 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.
PsilocybinObsessive-Compulsive Disorder (OCD)Older AdultsDepressive DisordersSafety & Risk ManagementPublic Health, Prevention & Behaviour ChangeThis 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.
EsketamineKetamineTreatment-Resistant Depression (TRD)Depressive DisordersSubstance Use Disorders (SUD)SuicidalitySafety & Risk ManagementThis 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).
KetamineDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Health Economics & ReimbursementPhase I single-group study (n=15) testing a second psilocybin-assisted group therapy session (oral psilocybin with optional booster) for anxiety/distress in partial responders with metastatic cancer.
PsilocybinMost respondents had previously received medication or psychotherapy for OCD. Psilocybin, LSD and MDMA were the most used substances, while reported symptom changes varied widely and were most favourable for classic serotonergic psychedelics.
LSDMDMAPsilocybinObsessive-Compulsive Disorder (OCD)This open-label crossover Phase I trial (n=12) evaluated the safety and efficacy of ketamine for bipolar disorder.
KetamineIn a double-blind, placebo-controlled resting-state fMRI study of 40 meditation practitioners, buccal DMT–harmine increased functional connectivity within the visual network and between visual and attention/salience networks, whereas meditation with placebo produced greater network segregation. No prolonged disruption of cortical gradients was observed, indicating a return to typical brain organisation shortly after the experience and pointing to distinct neural mechanisms — and potential clinical complementarities — between meditation and psychedelic-augmented meditation.
AyahuascaDMTPsilocybinNeuroimaging & Brain MeasuresDepressive DisordersPTSDSubstance Use Disorders (SUD)
Week of 22 September 2025
In a randomized, double-blind, placebo-controlled crossover in 23 healthy volunteers, MDA produced longer‑lasting, stronger and more psychedelic‑like subjective and autonomic effects and more adverse reactions than equimolar MDMA. Lys‑MDA acted as a functional slow‑release prodrug that delayed onset and peak effects, whereas Lys‑MDMA did not release MDMA and produced no measurable effects, showing lysine conjugation can alter timing but not necessarily improve tolerability.
MDMAHealthy VolunteersPTSDAdolescentsMedicinal Chemistry & Drug DevelopmentMindstate Design Labs’ oral MSD-001, a formulation of 5-MeO-MiPT, was safe and well tolerated at five doses in a Phase I trial at the Centre for Human Drug Research in the Netherlands. Participants reported heightened emotions, associative thinking and brighter colours, but not a classic psychedelic trip. Effects began after about 30 minutes and peaked at 90 minutes to two hours, with no serious adverse events reported.
MDMAPTSDRandomised, double-blind, placebo-controlled parallel trial (n=51 actual) testing repeated IV ketamine infusions (0.5 mg/kg, six 40-minute infusions) for depression in people with Parkinson's disease.
KetamineThis Phase I intervention trial (n=120) investigates whether stimulating the serotonin system influences pro-social behaviour compared to stimulating the dopamine system in healthy individuals; single-dose psilocybin (15 mg), MDMA (100 mg) or methylphenidate (60 mg) in a double-blind randomized parallel design.
PsilocybinMDMA
Week of 15 September 2025
In a single‑arm, open‑label pilot of 15 people with methamphetamine use disorder, outpatient psilocybin‑assisted psychotherapy (single 25 mg oral dose with preparatory and integration sessions) was feasible and well tolerated with no serious adverse events, and was associated with reductions in self‑reported methamphetamine use and craving at 28 and 90 days; a larger randomised trial is required to confirm efficacy and safety.
PsilocybinAnxiety DisordersDepressive DisordersSubstance Use Disorders (SUD)Headache Disorders (Cluster & Migraine)SuicidalitySchizophreniaSafety & Risk ManagementChronic PainThe UG3/UH3 grant will support lead optimisation, translational proof-of-concept studies, toxicology and manufacturing work for an Investigational New Drug application. The programme aims to identify candidates that retain activity against opioid use disorder while minimising hallucinogenic effects and avoiding 5-HT2B-related cardiac risks, with Phase 1 studies possible if milestones are met.
Opioid Use Disorder (OUD)Also covered by Psychedelic Alpha
This randomised controlled trial in 25 frontline physicians and nurses found that adding group psilocybin‑assisted psychotherapy (25 mg) to an 8‑week MBSR curriculum produced larger reductions in depressive symptoms at two weeks and greater improvements on burnout subscales, demoralisation and connectedness than MBSR alone. The intervention was well tolerated (only grade 1–2 adverse events, no serious AEs), suggesting that combining psilocybin with mindfulness training may be a promising treatment for COVID‑19‑related depression and burnout in healthcare providers.
PsilocybinDepressive DisordersSuicidalityAnxiety DisordersSafety & Risk ManagementThis interventional trial (n=30) will evaluate the efficacy and tolerability of a virtual reality-based mindfulness intervention combined with intranasal esketamine treatment compared to esketamine treatment alone in patients with treatment-resistant major depressive disorder (TRD). Participants will be randomly assigned to receive either the combined treatment (esketamine plus mindfulness) or standard esketamine treatment as usual, with the primary aim of assessing reductions in depressive symptoms. During the 4-week induction phase, both groups will receive intranasal esketamine, with the experimental group also participating in a 10-minute virtual reality mindfulness session prior to each treatment. Following this, the maintenance phase will last from weeks 5 to 30, with participants continuing esketamine administration once weekly for four weeks, followed by biweekly sessions. Key outcome measures will include changes in depressive symptom severity, inflammatory blood parameters, tolerability, and the duration of remission, with assessments conducted at baseline, the end of the induction phase, and at 30 and 54 weeks post-treatment.
EsketamineRandomised, parallel-arm trial (n=6 actual) comparing concurrent behavioural activation therapy plus intranasal esketamine versus esketamine alone for treatment-resistant depressive episodes in MDD or BD.
EsketamineThis Phase I, double-blind, active-controlled trial (n=40) will investigate the safety and potential therapeutic effects of co-administered MDMA and psilocybin in military Veterans diagnosed with post-traumatic stress disorder (PTSD).
MDMAPsilocybinIn two placebo-controlled studies, a single dose of MDMA (100 mg) increased participants’ feelings of global trust and marginally raised self-worth 90 minutes after a conversation, whereas methamphetamine (20 mg) produced no change. These results indicate MDMA uniquely enhances generalized social trust beyond lab-specific partners, supporting its potential social‑psychological clinical value.
MDMAInterpersonal Functioning & Social ConnectednessThis randomised, open‑label, parallel trial (n=106) will evaluate the efficacy and safety of a single intravenous esketamine infusion as adjunctive therapy to optimised pregabalin and venlafaxine in adults with fibromyalgia who have had insufficient symptom relief; the primary outcome is median pain relief time measured over a 12‑week follow‑up. The study’s purpose is treatment-focused, assessing whether adding a short‑term esketamine infusion produces faster or greater pain relief than optimisation of conventional therapy alone. Participants are randomised to either control therapy (pregabalin and venlafaxine with a dose‑escalation regimen to maximal tolerated or recommended doses — maximum daily pregabalin 450 mg and venlafaxine 225 mg) or the same regimen plus a single intravenous esketamine infusion given on the day of enrolment. Plasma concentrations of esketamine and its metabolites will be collected at the end of the infusion for limited characterisation of systemic exposure and exploratory exposure–response analyses. Pain will be assessed at 15 minutes, 1 hour and 3 hours after treatment termination, on days 1, 3 and 5, and at weeks 1, 2, 4, 8 and 12. Key eligibility criteria include adults ≥18 years meeting ACR fibromyalgia criteria with baseline average pain NRS ≥4; major exclusions include prior treatment with pregabalin or venlafaxine, prior intravenous ketamine/esketamine for chronic pain, significant psychiatric or medical contraindications, substance abuse, and pregnancy or lactation.
Esketamine
Week of 8 September 2025
This Phase I/II study (n=62 estimated) tests two fixed psilocybin doses (10 mg, then 25 mg, one month apart) combined with either 12-session PA-CBT or 6-session minimal supportive therapy in adults with major depressive disorder (MDD) to assess feasibility, acceptability and preliminary efficacy.
PsilocybinThis 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.
DMTNeuroimaging & Brain MeasuresThis PhaseII interventional trial (n=40), titled “MDMA-Assisted Cognitive Behavioral Therapy (CBT) Compared With Methamphetamine-Assisted CBT in Obsessive-Compulsive Disorder (OCD): A Phase II Study,” aims to assess the safety and preliminary effectiveness of MDMA-assisted cognitive behavioral therapy in participants diagnosed with obsessive-compulsive disorder (OCD).
MDMAThis observational trial (n=20) will study how ibogaine treatment delivered at licensed clinics outside the United States affects brain function and clinical symptoms in adults aged 21–65 with moderate–severe opioid use disorder. The primary aim is to evaluate neural changes using MRI, magnetic resonance spectroscopy (MRS) and electroencephalography (EEG), alongside psychometric measures of craving, withdrawal, mood, anxiety, pain and quality of life. Participants who are independently scheduled to receive legal ibogaine treatment will undergo research assessments at three time points (baseline and two post-treatment visits, including an early post-treatment assessment and a later follow-up approximately 4–6 weeks after baseline). MRI/MRS will include task-based fMRI to measure BOLD responses to opioid-related images, resting-state functional connectivity within reward circuitry, and Glx (glutamate+glutamine) concentrations in the nucleus accumbens and anterior insula. EEG will record spectral and complexity measures, and participants will complete validated questionnaires (e.g., VAS craving, SOWS, CEQ), provide urine toxicology and pregnancy tests, and be followed with additional urine samples at 3 and 6 months. The UCI research team will not provide ibogaine treatment but will perform the observational imaging and clinical assessments.
Ibogaine
Week of 1 September 2025
This open-label trial (n=10) will investigate the effects of a single dose of MDMA on social cognition in adults with Borderline Personality Disorder (BPD).
MDMAThe letter cites unreported adverse events at multiple sites, insufficient evidence of durable effects in chronic PTSD, and high prior MDMA use and prescreening failure rates among participants. It recommends a new trial focused on durability, bias reduction and safety characterisation, alongside consideration of an independent third-party audit of study records.
MDMAPTSDIn a randomised placebo‑controlled trial in healthy volunteers, repeated 15 µg LSD microdoses produced no overall analgesic effects on cold‑pressor pain tolerance or subjective pain ratings, despite increasing blood pressure and subjective drug effects. Post‑hoc analyses in participants without baseline ceiling effects suggested a transient increase in pain tolerance and reduced unpleasantness after the first dose, implying the dose may be below the threshold for consistent analgesia and that larger studies with higher doses are needed.
LSDHealthy VolunteersMicrodosingChronic PainHeadache Disorders (Cluster & Migraine)This observational study assessed how ready 136 low- and middle-income countries are to implement psychedelic-assisted mental health therapy using 34 criteria covering disease burden, mental health services, payment, legal rules and cultural familiarity. South Africa, Thailand, Mexico, Brazil and Jamaica ranked highest overall, while 25 countries did not score highly in any domain.
Health Economics & ReimbursementImplementation & Service DeliveryThis randomised, blinded, Phase III trial (n=156) will investigate MDMA-assisted psychotherapy (weight-based dosing with supplemental doses) versus dexamfetamine-, lorazepam-, diphenhydramine-, or placebo-assisted psychotherapy for social anxiety in autistic young people.
MDMAThis Phase I open-label trial (n=12) will investigate the safety, feasibility, and initial efficacy of intravenous psilocin (TRP-8803), administered in two doses (ranging from 6.7 mg to 15 mg) two weeks apart, paired with psychedelic-assisted psychotherapy for adults with binge eating disorder (BED).
PsilocybinThis open-label Phase I trial (n=12) evaluated the safety and efficacy of the intervention for binge eating disorder.
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.
PsilocybinAnxiety DisordersDepressive DisordersOlder AdultsChronic PainPalliative & End-of-Life DistressSafety & Risk ManagementThis 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.
LSDDepressive DisordersMajor Depressive Disorder (MDD)Anxiety DisordersPalliative & End-of-Life DistressSafety & Risk ManagementIn a phase 4, multicentre, double-blind randomised trial in adults with treatment‑resistant depression, intranasal esketamine monotherapy (56 mg and 84 mg) produced significant reductions in MADRS score versus placebo at day 28 (LS mean differences −5.1 and −6.8; effect sizes 0.48 and 0.63) and demonstrated rapid benefit at 24 hours. The tolerability profile was consistent with prior reports, most commonly nausea, dissociation, dizziness and headache.
EsketamineKetamineDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Headache Disorders (Cluster & Migraine)SuicidalitySchizophreniaSafety & Risk ManagementChronic PainThis 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.
PsilocybinSchizophreniaNeurocognitive DisordersIn this non-randomised, three-arm clinical trial of 84 adults bereaved within 12 months, ayahuasca-assisted meaning reconstruction therapy (A-MR) was well tolerated and produced significantly larger reductions in grief severity and greater improvements in prolonged grief symptoms, post‑traumatic growth and quality of life than meaning reconstruction alone or no treatment. These preliminary findings support A-MR as a potentially effective early intervention for severe grief but require replication in larger randomised trials.
AyahuascaDepressive DisordersSafety & Risk Management
Week of 25 August 2025
The 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.
KetamineThis 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).
PsilocybinMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersHealth Economics & ReimbursementIn a Phase 2, non-randomised open-label trial of 22 adults with PTSD, a single 25 mg dose of psilocybin administered with psychological support was generally well tolerated with no serious adverse events and mostly transient side-effects, and was associated with large, clinically meaningful reductions in PTSD symptoms and improvements in functioning and quality of life sustained to 12 weeks. These results indicate single-dose psilocybin may be safe and potentially efficacious for PTSD, warranting further controlled investigation.
PsilocybinDepressive DisordersPTSDTreatment-Resistant Depression (TRD)Headache Disorders (Cluster & Migraine)Safety & Risk ManagementChronic PainResilient Pharmaceuticals follows a roughly $50M recapitalisation led by Sir Chris Hohn and Antonio Gracias, with Mike Burke appointed CEO and Javier Muniz as CMO. The change comes alongside wider industry developments, including pushback over Norway’s off-label ketamine reimbursement decision and the AbbVie-Gilgamesh deal being viewed as validation for short-acting psychedelics.
KetamineAlso covered by The Guardian
Multicentre, randomised, non-inferiority, parallel-group open-label trial (n=340) comparing six adjunctive IV esketamine infusions (0.2 mg/kg, 40-minute infusion, three times/week) versus six ECT sessions over two weeks for reduction of suicidal ideation in depressive episodes.
EsketamineThis open-label Phase II trial (n=100) will study the safety, tolerability, and potential therapeutic effects of psilocybin (2 x 25 mg oral doses, taken at least 3 weeks apart) in the biological children of genocide survivors who are living with mood and anxiety disorders.
PsilocybinThis double-blind, randomized, placebo-controlled Phase II trial (n=200) investigates the therapeutic neural mechanisms of psilocybin (30mg) in patients with alcohol use disorder (AUD).
Psilocybin
Week of 18 August 2025
This open-label Phase II trial (n=200) evaluated the safety and efficacy of psilocybin for depression post-traumatic stress disorder.
PsilocybinMDMAUsing a decision-analysis model for 1,000 Ukrainian PTSD patients, the study estimates MDMA-assisted group therapy with supplemental individual sessions would cost US$1.1m, avert 19.2 deaths, gain 717 QALYs, have an ICER of US$1,537/QALY and produce net societal savings of US$2.6m, with scaled 50% coverage over 10 years potentially saving ~48,000 lives, 1.5 million QALYs and US$5.6bn. These results indicate MAT is likely to be cost‑effective or cost‑saving and could substantially improve population health, supporting its inclusion in Ukraine’s PTSD treatment strategy.
MDMAPTSDVeteransHealth Economics & ReimbursementPublic Health, Prevention & Behaviour ChangeLong-term ayahuasca users exhibited higher psychological resilience and distinct patterns of emotional brain reactivity on fMRI, with a machine-learning classifier separating users from controls at 75% accuracy and a regression model predicting individual resilience (r = 0.69). These findings suggest long-term ayahuasca use is associated with neural adaptations in emotional processing detectable by multivariate pattern analysis.
AyahuascaDMTNeuroimaging & Brain Measures
Week of 11 August 2025
In a double‑blind, placebo‑controlled within‑subject study using an ecologically valid painting task, an ayahuasca‑inspired DMT/harmine formulation impaired convergent thinking (particularly in participants with higher baseline reasoning) and showed trend‑level reductions in divergent fluency and elaboration. At the process level both DMT/HAR and harmine reduced incubation‑related transitions, while DMT/HAR uniquely decreased transitions from incubation to illumination, indicating psychedelics alter the dynamic pathways to creative insight and that subjective altered meaning and insightfulness selectively predict divergent but not convergent outcomes.
AyahuascaDMTCreativityIn this open-label exploratory crossover study of nine experienced ayahuasca users, three Acacia‑derived oral formulations delivering DMT plus harmala alkaloids were well tolerated, produced no clinically significant physiological changes, and elicited psychedelic effects rated comparable to (and for ACL‑010 sometimes more beneficial than) traditional ayahuasca. These findings suggest Acacia‑based DMT/harmala formulations are a feasible alternative for future clinical trials, although generalisability is limited by the small sample size and open‑label design.
AyahuascaDMTHealthy VolunteersAnxiety DisordersSubstance Use Disorders (SUD)Headache Disorders (Cluster & Migraine)Safety & Risk ManagementMedicinal Chemistry & Drug DevelopmentPersonality & Trait FactorsChronic PainIn an open letter, MAPS called on HHS Secretary Robert F. Kennedy Jr. and FDA Commissioner Martin A. Makary to prioritise regulatory reform, citing successful Phase 3 trials and continued inaccessibility. It highlighted collaboration with the VA, NYU, Harvard and UCSF, alongside legal access efforts in Oregon and Colorado.
MDMAPTSDThis systematic review and meta-analysis of oral ketamine for major depression (10 studies; meta-analysis of three RCTs, N=161) found a significant antidepressant effect (SMD −0.75). The paper also summarises tolerability data but emphasises that the evidence base is small and further high-quality trials are needed.
KetamineDepressive DisordersMajor Depressive Disorder (MDD)For the quarter ended 30 June 2025, Filament Health reported $259,013 in revenue, $679,972 in cash and $592,136 used in operating activities. It secured an exclusive global licence from the University of Alabama at Birmingham covering intellectual property and data from a Phase 2 psilocybin study in cocaine use disorder, while Swedish authorities approved a double-blind Phase 2 PEX010 trial at Linköping University for prolonged grief disorder. PEX010 also received compassionate-use approval in Germany for treatment-resistant depression.
PsilocybinDepressive DisordersTreatment-Resistant Depression (TRD)
Week of 4 August 2025
GH Research said one topic remains in discussions with the FDA over the GH001 clinical hold, while a GH002 IND submission is planned for Q4 2025. In treatment-resistant depression, the Phase 2b GH001 trial showed a placebo-adjusted MADRS reduction of 15.5 points on Day 8, and its six-month open-label extension recorded a 73% remission rate with no treatment-related serious adverse events.
This triple-blind, randomised, placebo-controlled trial (n=60) will study the role of neuroplasticity in the behavioural effects of psilocybin in individuals with mild declines in emotional wellbeing. Participants will receive one of four medication combinations (25 mg or 1 mg psilocybin with IV midazolam or IV saline).
PsilocybinIn a preliminary uncontrolled study of 21 veterans with traumatic brain injury, participation in two psilocybin retreat ceremonies was associated with large reductions in PTSD, depression and anxiety symptoms and with EEG changes (reduced frontal/temporal delta–theta power and increased alpha–beta coherence) consistent with improved emotional regulation and neural communication. These findings suggest psilocybin retreats may improve psychological wellbeing and brain connectivity in veterans with TBI and warrant larger, controlled trials.
PsilocybinAnxiety DisordersDepressive DisordersPTSDVeteransTraumatic Brain Injury (TBI)Neurological InjuryNeuroimaging & Brain MeasuresThis randomised, placebo-controlled, quadruple-masked trial (n=112) will investigate whether the antidepressant effects of DMT (2 mg/min over 20 minutes; total ~40 mg) in patients with MDD depend on the subjective psychedelic experience by comparing DMT vs placebo under propofol sedation or no sedation.
DMTThis double-blind, randomized, placebo-controlled, parallel-group laboratory trial (n=63) conducted by Yale University aims to determine the effects of DMT (14-21mg/70kg/min) infusions, in conjunction with psychotherapy, on Alcohol Use Disorder (AUD).
DMTThis 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.
IbogaineDepressive Disorders
Week of 28 July 2025
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.
PsilocybinAnxiety DisordersMajor Depressive Disorder (MDD)Depressive DisordersHealthy VolunteersThis 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.
DMTHealthy VolunteersMedicinal Chemistry & Drug DevelopmentPersonality & Trait FactorsImplementation & Service DeliveryThis 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.
LSDPsilocybinDMT5-MeO-DMTAyahuascaMescalineTobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)SuicidalityMicrodosingThis 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.
EsketamineKetamineDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Anxiety DisordersTobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Palliative & End-of-Life DistressSafety & Risk ManagementThis 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.
5-MeO-DMTBipolar DisorderDepressive DisordersAlcohol Use Disorder (AUD)Neuroimaging & Brain MeasuresHealthy VolunteersSubstance Use Disorders (SUD)Germany has granted approval for PEX010 to be used outside a clinical trial, which Filament Health described as the first such EU authorisation for psilocybin. Dr Gerhard Gründer will administer the treatment at the Central Institute of Mental Health’s Department of Molecular Neuroimaging.
PsilocybinDepressive DisordersNeuroimaging & Brain MeasuresTreatment-Resistant Depression (TRD)Also covered by Filament
This randomised, open-label, parallel arm trial (n=40) will examine the potential synergy between psilocybin (25 mg, single dose) and 8 weeks of mindfulness training versus psilocybin alone in healthy adults.
PsilocybinSingle-masked, randomised controlled trial (n=60) comparing psilocybin (two high-dose oral sessions, 5–6 g each, six weeks apart), CBT (8–10 sessions), psilocybin-assisted CBT, and routine care in adults with MDD.
PsilocybinThis Phase II, randomised, triple-blind, active-dose-controlled trial (n=100) is evaluating RE104 in adults with adjustment disorder related to cancer or another serious medical illness, including ALS, multiple sclerosis, Parkinson’s disease or idiopathic pulmonary fibrosis. Participants receive a single subcutaneous injection of either 30 mg RE104 or a 1.5 mg active-control dose. The trial is designed to determine whether RE104 reduces depressive symptoms, including depressive symptoms mixed with anxiety. The primary outcome compares change from baseline in Montgomery-Åsberg Depression Rating Scale total score between the two dose groups at Day 7, with additional efficacy and safety follow-up.
PsilocybinThis meta-analysis of 17 trials found that control-group participants in psilocybin depression trials showed markedly smaller improvements (SMC ≈ 0.50) on the MADRS than control participants in SSRI (SMC ≈ 1.00) or esketamine (SMC ≈ 1.12) trials. The authors conclude this disparity may indicate that psilocybin’s antidepressant efficacy is overestimated relative to SSRIs and esketamine, possibly because of functional unblinding and expectancy effects.
EsketamineKetaminePsilocybinAnxiety DisordersDepressive DisordersOlder AdultsMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)
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