2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/2iy5wruuedsh6.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/00yc7rcvua6a7.js","/_next/static/immutable/chunks/37ktb71aq3480.js","/_next/static/immutable/chunks/2d50b-7eu4558.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/2d6noqpp6ehas.js","/_next/static/immutable/chunks/1sx186c93bpzg.js","/_next/static/immutable/chunks/3dc-1n866s65i.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2w1bvggzb0ga8.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T6a8, Non-human models, including fish, are increasingly important for investigating how pharmacological agents such as hallucinogens influence behavior, physiology, and cellular processes. These models help to reveal underlying mechanisms and to support assessments of toxicological impact, efficacy, and safety. In this study, we used isogenic lineages of the amphibious mangrove rivulus ( Kryptolebias marmoratus ), an emerging model fish known for high activity and socially dynamic interactions. This species often display aggression towards conspecifics making it well-suited to study behavioral effects of low doses of the psychoactive compound, psilocybin. We determined whether psilocybin could induce calming effects and reduce social aggression and activity. We socially stimulated fish using pairs of size-matched fish from different isogenic lineages and compared baseline social behavior following a waterborne dose of psilocybin. Waterborne psilocybin treatment resulted in a significant decrease in activity levels and in the frequency of swimming bursts (an aggressive behavior) towards a conspecific fish from a different lineage, with modest alterations on other behaviors. Our results also revealed considerable intraspecific variation in the behavioral response of these homozygous fish, suggesting the effects of psilocybin were largely independent of genotype. This study demonstrates that psilocybin reduces aggression and activity in an emerging fish model, adding to the evidence supporting its potential as a therapeutic agent for future clinical translation. 31:T489,A total of 144 participants (mean [SD] age, 42.6 [10.8] years; 85 male [59.0%]) were randomized, and 142 were included in the primary efficacy analysis: psilocybin, 25 mg (n = 47), psilocybin, 5 mg (n = 48), and nicotinamide (n = 47). Response rates on the primary end point were 17.0% in the group receiving psilocybin, 25 mg; 12.5% in the group receiving psilocybin, 5 mg; and 10.6% in the group receiving nicotinamide. The first hierarchical comparison was nonsignificant (psilocybin, 25 mg vs nicotinamide, adjusted odds ratio [OR], 1.73; 95% CI, 0.53-6.23; P = .19; 1-sided α P = .03); consequently, further formal testing was not performed. Analyses of key secondary end points (mean changes from baseline on HAMD17 and BDI-II) provided exploratory evidence of a clinically meaningful effect of psilocybin, 25 mg. Psilocybin, 25 mg, was linked to adverse events, predominantly acutely, and was associated with higher reports of suicidal ideation on dosing days (4% vs 1%-2% in comparator conditions). Two serious adverse reactions were reported after psilocybin, 25 mg, including 1 case of hallucinogen persisting perception disorder.32:Tbef,Psilocybin shows promise in treating depression, although limitations of previous research warrant further research. To investigate the efficacy and safety of oral psilocybin, 25 mg, with adjunct psychotherapy in treatment-resistant depression (TRD). This was a 2-center, triple-blinded (investigator, participant, rater), phase 2b, active placebo-controlled randomized clinical trial. Participants were randomized to 4 groups in ratios 2:2:1:1, receiving 2 doses 6 weeks apart (week 0, week 6) as follows: (1) placebo (nicotinamide, 100 mg) then psilocybin, 25 mg; (2) psilocybin, 5 mg, then 25 mg; and (3) psilocybin, 25 mg, then 5 mg or psilocybin, 25 mg, twice embedded in psychotherapeutic sessions. Participants aged 25 to 65 years with TRD and withdrawn from antidepressant medication were recruited predominantly from 2 outpatient settings in Germany. Study data were analyzed from April 2024 to November 2025. Oral synthetic psilocybin, 25 mg; psilocybin, 5 mg; or nicotinamide, 100 mg administered with psychotherapeutic sessions. The primary end point was treatment response (≥50% reduction on the Hamilton Rating Scale for Depression [HAMD17]) at week 6 before the second dose. Key secondary end points were response on the Beck Depression Inventory II (BDI-II) and mean change from baseline on the HAMD17 and BDI-II at week 6. A total of 144 participants (mean [SD] age, 42.6 [10.8] years; 85 male [59.0%]) were randomized, and 142 were included in the primary efficacy analysis: psilocybin, 25 mg (n = 47), psilocybin, 5 mg (n = 48), and nicotinamide (n = 47). Response rates on the primary end point were 17.0% in the group receiving psilocybin, 25 mg; 12.5% in the group receiving psilocybin, 5 mg; and 10.6% in the group receiving nicotinamide. The first hierarchical comparison was nonsignificant (psilocybin, 25 mg vs nicotinamide, adjusted odds ratio [OR], 1.73; 95% CI, 0.53-6.23; P = .19; 1-sided α P = .03); consequently, further formal testing was not performed. Analyses of key secondary end points (mean changes from baseline on HAMD17 and BDI-II) provided exploratory evidence of a clinically meaningful effect of psilocybin, 25 mg. Psilocybin, 25 mg, was linked to adverse events, predominantly acutely, and was associated with higher reports of suicidal ideation on dosing days (4% vs 1%-2% in comparator conditions). Two serious adverse reactions were reported after psilocybin, 25 mg, including 1 case of hallucinogen persisting perception disorder. In this randomized clinical trial, psilocybin, 25 mg, with adjunct psychotherapy, was associated with a clinically meaningful reduction in depressive symptoms in individuals with TRD, although findings did not show a significant effect on the primary outcome. The treatment was well tolerated by most participants, although safety signals were observed. While overall this constituted an inconclusive trial, these results add to the existing evidence on the potential of psilocybin treatment for depression. ClinicalTrials.gov Identifier: NCT04670081.33:T126e, Importance Psilocybin shows promise in treating depression, although limitations of previous research warrant further research. Objective To investigate the efficacy and safety of oral psilocybin, 25 mg, with adjunct psychotherapy in treatment-resistant depression (TRD). Design, Setting, and Participants This was a 2-center, triple-blinded (investigator, participant, rater), phase 2b, active placebo-controlled randomized clinical trial. Participants were randomized to 4 groups in ratios 2:2:1:1, receiving 2 doses 6 weeks apart (week 0, week 6) as follows: (1) placebo (nicotinamide, 100 mg) then psilocybin, 25 mg; (2) psilocybin, 5 mg, then 25 mg; and (3) psilocybin, 25 mg, then 5 mg or psilocybin, 25 mg, twice embedded in psychotherapeutic sessions. Participants aged 25 to 65 years with TRD and withdrawn from antidepressant medication were recruited predominantly from 2 outpatient settings in Germany. Study data were analyzed from April 2024 to November 2025. Interventions Oral synthetic psilocybin, 25 mg; psilocybin, 5 mg; or nicotinamide, 100 mg administered with psychotherapeutic sessions. Main Outcomes and Measures The primary end point was treatment response (≥50% reduction on the Hamilton Rating Scale for Depression [HAMD17]) at week 6 before the second dose. Key secondary end points were response on the Beck Depression Inventory II (BDI-II) and mean change from baseline on the HAMD17 and BDI-II at week 6. Results A total of 144 participants (mean [SD] age, 42.6 [10.8] years; 85 male [59.0%]) were randomized, and 142 were included in the primary efficacy analysis: psilocybin, 25 mg (n = 47), psilocybin, 5 mg (n = 48), and nicotinamide (n = 47). Response rates on the primary end point were 17.0% in the group receiving psilocybin, 25 mg; 12.5% in the group receiving psilocybin, 5 mg; and 10.6% in the group receiving nicotinamide. The first hierarchical comparison was nonsignificant (psilocybin, 25 mg vs nicotinamide, adjusted odds ratio [OR], 1.73; 95% CI, 0.53-6.23; P = .19; 1-sided α P = .03); consequently, further formal testing was not performed. Analyses of key secondary end points (mean changes from baseline on HAMD17 and BDI-II) provided exploratory evidence of a clinically meaningful effect of psilocybin, 25 mg. Psilocybin, 25 mg, was linked to adverse events, predominantly acutely, and was associated with higher reports of suicidal ideation on dosing days (4% vs 1%-2% in comparator conditions). Two serious adverse reactions were reported after psilocybin, 25 mg, including 1 case of hallucinogen persisting perception disorder. Conclusion and Relevance In this randomized clinical trial, psilocybin, 25 mg, with adjunct psychotherapy, was associated with a clinically meaningful reduction in depressive symptoms in individuals with TRD, although findings did not show a significant effect on the primary outcome. The treatment was well tolerated by most participants, although safety signals were observed. While overall this constituted an inconclusive trial, these results add to the existing evidence on the potential of psilocybin treatment for depression. Trial Registration ClinicalTrials.gov Identifier: NCT04670081 34:Tc18,Binge Eating Disorder (BED) is the most prevalent eating disorder and is associated with psychiatric comorbidities, health impairments, and decreased quality of life. Emerging evidence suggests that psilocybin-assisted therapy may promote cognitive and emotional flexibility and disrupt maladaptive behavioral patterns, making it a promising candidate for BED treatment. This open-label pilot study evaluated the feasibility, safety, and preliminary therapeutic effects of a single 25 mg dose of psilocybin administered in the context of Acceptance and Commitment Therapy (ACT)-based psychotherapy in adults with BED (N = 5). Primary outcomes included safety measures, and exploratory outcomes included self-reported binge eating frequency, depression, anxiety, psychological flexibility, anthropometric indices, and neuroimaging biomarkers assessed over a 14-week follow-up. Psilocybin was well tolerated, with no serious adverse events. Reductions in self-reported binge eating frequency were observed across all participants and sustained through week 14. Improvements were also noted in depression, anxiety, and psychological inflexibility. Three participants showed reductions in body mass index and waist circumference. Given the open label design and small sample size, causality cannot be inferred. fMRI analyses generated preliminary signals of change-such as increased functional activation from pre- to post-intervention in the middle frontal gyrus, angular gyrus, and supramarginal gyrus in response to processed versus unprocessed food cues. Psilocybin-assisted therapy was feasible and well-tolerated in individuals with BED. The clinical and neurobiological observations provide directions for future adequately powered trials. Binge Eating Disorder (BED) is the most common eating disorder and can have a serious impact on mental health, physical health, and overall quality of life. Many people with BED struggle with repeated patterns of eating that feel hard to change, even when they want to. New treatments are needed to help people break these cycles in safe and supportive ways. This small pilot study explored whether a single dose of psilocybin, given alongside a type of talk therapy focused on values, acceptance, and behavior change, could be safely used with adults who have BED. Five adults took part in the study and were followed for about three months. The treatment was well tolerated, and no serious safety concerns were found. All participants reported fewer binge eating episodes after the treatment, and these improvements lasted throughout the follow-up period. Many also reported feeling less depressed and anxious and more able to respond flexibly to difficult thoughts and emotions. Some participants showed small reductions in weight and waist size. Brain scans suggested possible changes in how participants responded to food-related images. Because this was a small study without a comparison group, stronger conclusions cannot yet be made. However, the findings suggest this approach may be promising and worth studying further in larger trials.35:T787,Abstract Binge Eating Disorder (BED) is the most prevalent eating disorder and is associated with psychiatric comorbidities, health impairments, and decreased quality of life. Emerging evidence suggests that psilocybin-assisted therapy may promote cognitive and emotional flexibility and disrupt maladaptive behavioral patterns, making it a promising candidate for BED treatment. This open-label pilot study evaluated the feasibility, safety, and preliminary therapeutic effects of a single 25 mg dose of psilocybin administered in the context of Acceptance and Commitment Therapy (ACT)-based psychotherapy in adults with BED ( N = 5). Primary outcomes included safety measures, and exploratory outcomes included self-reported binge eating frequency, depression, anxiety, psychological flexibility, anthropometric indices, and neuroimaging biomarkers assessed over a 14-week follow-up. Psilocybin was well tolerated, with no serious adverse events. Reductions in self-reported binge eating frequency were observed across all participants and sustained through week 14. Improvements were also noted in depression, anxiety, and psychological inflexibility. Three participants showed reductions in body mass index and waist circumference. Given the open label design and small sample size, causality cannot be inferred. fMRI analyses generated preliminary signals of change—such as increased functional activation from pre- to post-intervention in the middle frontal gyrus, angular gyrus, and supramarginal gyrus in response to processed versus unprocessed food cues. Psilocybin-assisted therapy was feasible and well-tolerated in individuals with BED. The clinical and neurobiological observations provide directions for future adequately powered trials. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"psilocybin: generic Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on psilocybin (generic). Clinician-written summaries and actionable practice insights. 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A meta-analysis confirmed acute anxiety adverse events were transient, resolving within 48 hours.","limitations":"- Full text was not available; summary is based on the publisher preview only.\n- Direct clinical evidence in primary anxiety disorders (outside cancer-related anxiety) remains limited.\n- The article is a short 'Hot Topics' commentary, not a primary trial or full systematic review.","practice_takeaway":"Psilocybin shows large and durable anxiolytic effects in cancer-related anxiety, with acute side effects resolving within 48 hours—but evidence in broader anxiety disorder populations is still sparse. Clinicians should monitor emerging trials before incorporating psilocybin into practice for general anxiety disorders."}},{"doi":"10.1177/02698811261478603","pmid":"42668404","title":"A randomized crossover trial comparing the acute physiological and psychological effects of botanical formulations of oral psilocybin, oral psilocin, and sublingual psilocin","journal_title":"Journal of Psychopharmacology","journal_issn":"0269-8811","published_at":"2026-08-29T00:00:00.000Z","url":"https://doi.org/10.1177/02698811261478603","source_score":22,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-06T06:23:11.184Z","updated_at":"2026-09-06T06:23:11.184Z","tags":[{"paper_doi":"10.1177/02698811261478603","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"condition","value":"Healthy Volunteers","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"generic","value":"psilocin","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"modality","value":"Serotonergic Psychedelic","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"sample_size","value":"n=20","value_numeric":20},{"paper_doi":"10.1177/02698811261478603","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"study_design","value":"Randomized Crossover Trial","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"warning","value":"Level of evidence assigned as 2 (crossover RCT in healthy volunteers); clinical therapeutic applicability is indirect at this stage.","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"warning","value":"The sublingual psilocin arm tested multiple dose levels (2.18, 4.36, 8 mg), but the abstract does not specify how many sessions per participant or exact crossover allocation — some within-group comparisons may be underpowered.","value_numeric":null},{"paper_doi":"10.1177/02698811261478603","tag_type":"warning","value":"The trial used botanical (whole-mushroom extract) formulations, so findings may not directly apply to synthetic psilocybin or psilocin used in most clinical trials.","value_numeric":null}],"summaries":{"what_studied":"This randomized, within-subject crossover trial in 20 healthy adults compared the acute pharmacodynamic profiles and tolerability of botanical oral psilocybin (25 mg), oral psilocin (17.5 mg), and sublingual psilocin (2.18, 4.36, or 8 mg) derived from whole-mushroom extracts, with all sessions including therapeutic support and psychotherapy.","key_result":"Oral psilocin produced a similar temporal and subjective psychedelic profile to oral psilocybin but with a lower burden of adverse effects; sublingual psilocin was well tolerated at all doses tested, though lower apparent drug exposure limited direct comparison to oral routes.","limitations":"- Very small sample (n=20), limiting generalizability.\n- Lower sublingual drug exposure prevented head-to-head dose equivalence comparisons with oral formulations.\n- Healthy adult volunteers only — findings may not translate to clinical/patient populations.","practice_takeaway":"Oral psilocin from botanical extracts may be a better-tolerated alternative to oral psilocybin with a comparable psychedelic profile, warranting further investigation. Sublingual psilocin shows early tolerability promise but optimal dosing for therapeutic use remains undefined."}},{"doi":"10.1007/s00213-026-07138-0","pmid":"42649324","title":"Pilot study comparing the effects of high dose THC to high dose psilocybin and placebo in the set and setting of a classic psychedelic therapy session","journal_title":"Psychopharmacology","journal_issn":"0033-3158","published_at":"2026-08-27T00:00:00.000Z","url":"https://doi.org/10.1007/s00213-026-07138-0","source_score":21,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-03T06:19:51.072Z","updated_at":"2026-09-03T06:19:51.072Z","tags":[{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"brand","value":"Marinol","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"condition","value":"Healthy Volunteers","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"generic","value":"delta-9-tetrahydrocannabinol","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"generic","value":"dronabinol","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"modality","value":"Cannabinoid","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"modality","value":"Psychedelic","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"sample_size","value":"n=4","value_numeric":4},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"study_design","value":"Crossover Trial","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"warning","value":"Dronabinol (Marinol) is listed as the brand equivalent for synthetic THC used; the paper does not explicitly name the brand, so this is inferred from the generic name.","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"warning","value":"One participant gave very high MEQ scores after placebo, suggesting strong expectancy effects that complicate interpretation of drug comparisons.","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"warning","value":"Participants were exclusively white, non-Hispanic, and mostly highly educated — findings may not generalize broadly.","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"warning","value":"Sample size of n=4 makes all findings purely hypothesis-generating; no inferential statistics were performed.","value_numeric":null},{"paper_doi":"10.1007/s00213-026-07138-0","tag_type":"warning","value":"Study design is labeled 'Crossover Trial' rather than 'Randomized Controlled Trial' because randomization applied only to drug order and THC source, and the sample is too small for standard RCT classification.","value_numeric":null}],"summaries":{"what_studied":"This double-blind, placebo-controlled crossover pilot study (n=4 healthy adults, ages 31–47, 3 female) compared the acute subjective effects of oral placebo, psilocybin (25 mg), and oral Δ9-THC (25 mg and 50 mg, as either synthetic dronabinol or cannabis distillate) administered under the set and setting conditions of a standard psychedelic clinical trial.","key_result":"25 mg oral Δ9-THC (both dronabinol and distillate) produced Mystical Experience Questionnaire (MEQ) and 11D-ASC scores qualitatively similar to 25 mg psilocybin; dronabinol at 25 mg was mistaken for a classic hallucinogen by 2 of 4 participants (one psychedelic-naïve, one psychedelic-experienced). At 50 mg, dronabinol was correctly identified as a cannabinoid, while 50 mg distillate was perceived as sedative/dissociative with moderate psychedelic similarity.","limitations":"- Extremely small sample (n=4), all white/non-Hispanic, three with graduate degrees — severely limits generalizability.\n- Set and setting were held constant; the contribution of pharmacology vs. expectancy cannot be fully disentangled.\n- No inferential statistics possible; results are purely descriptive.","practice_takeaway":"For clinicians running psychedelic trials, oral Δ9-THC (particularly 25 mg dronabinol) may warrant evaluation as an active comparator to improve blinding integrity — though this pilot is far too small to guide practice on its own. Be aware that high-dose oral THC under psychedelic-style session conditions can produce unexpectedly prolonged effects and nausea, especially at 50 mg."}},{"doi":"10.1001/jamanetworkopen.2026.30608","pmid":"42616497","title":"Safety and Mental Health Outcomes of Oregon State-Regulated Psilocybin Services","journal_title":"JAMA Network Open","journal_issn":"2574-3805","published_at":"2026-08-19T00:00:00.000Z","url":"https://doi.org/10.1001/jamanetworkopen.2026.30608","source_score":576,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-24T06:18:13.182Z","updated_at":"2026-08-24T06:18:13.182Z","tags":[{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"condition","value":"Anxiety","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"condition","value":"Depression","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"condition","value":"Post-Traumatic Stress Disorder","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"modality","value":"Psychedelic-Assisted Therapy","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"sample_size","value":"n=346","value_numeric":346},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"warning","value":"Adverse behavioral reactions were statistically significant per the abstract, but the absolute rate (1.2%) is low; clinical significance of this rate in broader implementation contexts is uncertain.","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"warning","value":"Dose information was facilitator-reported; participant-reported outcomes were self-assessed with no independent verification.","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"warning","value":"No control or comparator group was used; pre-to-post improvements cannot be attributed to psilocybin alone due to potential expectancy, placebo, and regression-to-the-mean effects.","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"warning","value":"The sample is not representative of the general population—it skews White, highly educated, and high-income, which substantially limits generalizability.","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.30608","tag_type":"warning","value":"The study covers only up to 3 months of follow-up for primary outcomes; longer-term safety and durability of mental health benefits are not yet reported.","value_numeric":null}],"summaries":{"what_studied":"This multisite cohort study (OPEN) enrolled 346 adults receiving Oregon state-regulated psilocybin services at 24 licensed centers (Nov 2024–Mar 2026), supervised by 83 facilitators. It tracked safety events, and participant-reported depression (PHQ-9), anxiety (HADS), PTSD (PCL-6), mental well-being, and life satisfaction at baseline, 1 week, 1 month, and 3 months post-session.","key_result":"Serious adverse behavioral reactions requiring medical attention occurred in 4 of 346 participants (1.2%), all psychedelic-naive. At 3 months, moderate-to-severe depression fell by 60% (RR 0.40; 95% CI 0.32–0.50), anxiety by 71% (RR 0.29; 95% CI 0.22–0.38), and PTSD symptoms by 65% (RR 0.35; 95% CI 0.27–0.45) vs. baseline. Life satisfaction improved (RR 1.31; 95% CI 1.19–1.44) and mental well-being scores rose by 3.21 points (95% CI 2.66–3.76). At 1 month, 92.2% reported benefit and 58.6% ranked the session among the 10 most meaningful experiences of their life.","limitations":"- No control group; pre–post changes may partly reflect regression to the mean, natural history, or expectancy effects.\n- Sample was highly educated (76.6% college graduates), predominantly White (86.7%), and high-income (29% >$200K/year), limiting generalizability.\n- Outcomes are entirely self-reported; no blinding or independent outcome verification.","practice_takeaway":"In this real-world Oregon cohort, regulated psilocybin sessions appeared safe for most adults, with serious adverse reactions concentrated in psychedelic-naive users—clinicians counseling patients considering these services should flag psychedelic-naive status as a key risk factor. Large self-reported improvements in depression, anxiety, and PTSD are encouraging but must be interpreted cautiously given the uncontrolled design."}},{"doi":"10.1038/s41380-026-03777-z","pmid":"42521762","title":"Convergent neuroimmune signaling underlying rapid antidepressant response to ketamine and psychedelics","journal_title":"Molecular Psychiatry","journal_issn":"1359-4184","published_at":"2026-07-28T00:00:00.000Z","url":"https://doi.org/10.1038/s41380-026-03777-z","source_score":36,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:17:55.052Z","updated_at":"2026-08-04T18:17:55.052Z","tags":[{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"brand","value":"Ketamine","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"condition","value":"Major Depressive Disorder","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"condition","value":"Treatment-Resistant Depression","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"generic","value":"hydroxynorketamine","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"generic","value":"ketamine","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"generic","value":"lysergic acid diethylamide","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"modality","value":"NMDA Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"modality","value":"Serotonergic Psychedelic","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"sample_size","value":"n=64","value_numeric":64},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"study_design","value":"Multimodal Translational Study (Proteomics, Transcriptomics, Neuroimaging, Cytokine Analysis)","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"warning","value":"LSD and psilocybin were used only in iPSC in vitro models, not administered to human participants in this study.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"warning","value":"Sample sizes differ substantially across modalities (MEG n=55, transcriptomics n=27, cytokines n=64); the 'n=64' used for sample_size tag reflects the largest cohort (plasma cytokines), which may not represent the full study.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"warning","value":"Study design is complex and multimodal—labeling as a single study design is an approximation; it combines observational clinical data with in vitro iPSC experiments.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03777-z","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously—findings are mechanistic and biomarker-level; clinical translation requires prospective validation.","value_numeric":null}],"summaries":{"what_studied":"This study investigated shared molecular mechanisms underlying rapid antidepressant effects of ketamine and serotonergic psychedelics (LSD, psilocybin) in treatment-resistant depression (TRD), using CSF proteomics from healthy volunteers (HVs), iPSC-derived neurons, whole-blood transcriptomics, plasma cytokines, and MEG neuroimaging in TRD and HV participants receiving IV ketamine (0.5 mg/kg) or placebo.","key_result":"IL-15 and MCP-1 emerged as conserved immune hubs across CSF and iPSC data; plasma IL-7 correlated with baseline MEG gamma power brain-wide (pFDR < 0.05), with the strongest effect in TRD subcortical regions (pFDR < 10⁻¹⁴); post-ketamine, the IL-7–gamma relationship inverted alongside widespread gamma reductions in default-mode network regions; cytokine ratios predicted response (IL-4/IFN-γ, pFDR < 0.041) and non-response (MCP-1/IL-7, pFDR < 0.009).","limitations":"- Healthy volunteer CSF proteomics cannot fully represent TRD biology, and iPSC models may not recapitulate in vivo neuronal complexity.\n- Sample sizes vary considerably across modalities (transcriptomics n=27, MEG n=55, plasma cytokines n=64), limiting cross-modal comparisons.\n- The study is observational/mechanistic rather than a powered clinical trial, so causal relationships between cytokine shifts and antidepressant response remain inferential.","practice_takeaway":"The IL-7/IL-15 cytokine axis—measurable in plasma—may serve as a clinically accessible biomarker to predict and monitor rapid antidepressant response to ketamine; specifically, a high MCP-1/IL-7 ratio may flag likely non-responders before treatment. Validation in larger prospective cohorts is needed before clinical application."}},{"doi":"10.1038/s41380-026-03768-0","pmid":"42498781","title":"Time-dependent effects of rapid-acting antidepressants in iPSC-derived neurons from treatment-resistant depression and healthy volunteers","journal_title":"Molecular Psychiatry","journal_issn":"1359-4184","published_at":"2026-07-24T00:00:00.000Z","url":"https://doi.org/10.1038/s41380-026-03768-0","source_score":32,"is_retracted":false,"is_open_access":null,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":false},"created_at":"2026-08-01T13:21:52.910Z","updated_at":"2026-08-01T13:21:52.910Z","tags":[{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"condition","value":"Treatment-Resistant Depression","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"generic","value":"2,5-Dimethoxy-4-iodoamphetamine","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"generic","value":"hydroxynorketamine","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"generic","value":"ketamine","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"generic","value":"lysergic acid diethylamide","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"modality","value":"NMDA Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"modality","value":"Serotonergic Psychedelic","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"study_design","value":"In Vitro Experimental Study with Translational Validation","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"warning","value":"LSD and DOI are research compounds not approved for clinical use; clinical applicability of findings for these agents is highly speculative.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"warning","value":"No sample size (N) for the iPSC donor cohort is reported in the abstract; the sample_size tag was omitted.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"warning","value":"Sex of iPSC donors is not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03768-0","tag_type":"warning","value":"Study design is primarily in vitro (cell culture); the 'translational validation' component uses a separate human CSF proteomics dataset, which may introduce confounds.","value_numeric":null}],"summaries":{"what_studied":"iPSC-derived cortical-like neurons from individuals with treatment-resistant depression (TRD) and healthy volunteers (HVs) were treated for 6 and 24 h with four putative rapid-acting antidepressants — (2R,6R)-HNK, psilocybin, LSD, and DOI — and assessed via bulk and single-cell RNA sequencing, Western blotting, immunocytochemistry, and comparison to CSF proteomics from ketamine-treated HVs.","key_result":"Despite distinct initial pharmacological targets, gene expression profiles across all four compounds were highly correlated at matched timepoints vs. vehicle, converging on inflammation, mTORC1 signaling, and cellular growth pathways; (2R,6R)-HNK uniquely showed excitatory neuron upregulation and inhibitory neuron downregulation, and its transcriptomic signature overlapped with CSF proteomic data from ketamine-treated humans.","limitations":"- iPSC-derived neurons are an in vitro model and may not fully recapitulate in vivo brain complexity or cell-type diversity.\n- TRD vs. HV group-specific differences are not prominently detailed, limiting conclusions about disease-specific drug responses.\n- CSF proteomics comparison used HVs treated with ketamine, not TRD patients, constraining direct translational inference.","practice_takeaway":"Rapid-acting antidepressants from both glutamatergic and serotonergic classes converge on shared molecular pathways (mTORC1, inflammation) in human neurons, supporting their grouped investigation in TRD. iPSC-derived neuron platforms show early promise for antidepressant drug discovery but are not yet ready to replace clinical validation."}},{"doi":"10.1177/02698811261464988","pmid":"42460632","title":"Silence is golden: Documenting the speech production of participants and support providers in psilocybin administration sessions for the treatment of post-traumatic stress disorder","journal_title":"Journal of Psychopharmacology","journal_issn":"0269-8811","published_at":"2026-07-16T00:00:00.000Z","url":"https://doi.org/10.1177/02698811261464988","source_score":78,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-20T13:36:07.259Z","updated_at":"2026-07-20T13:36:07.259Z","tags":[{"paper_doi":"10.1177/02698811261464988","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"brand","value":"COMP360","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"condition","value":"Post-Traumatic Stress Disorder","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"modality","value":"Psychedelic-Assisted Therapy","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"sample_size","value":"n=22","value_numeric":22},{"paper_doi":"10.1177/02698811261464988","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"study_design","value":"Mixed-Methods Clinical Trial Analysis","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"warning","value":"Level of evidence rated '3' reflecting a secondary analysis of a small single-arm trial with qualitative components.","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"warning","value":"Sex breakdown of the 22 participants is not reported in the abstract; 'mixed' is assumed.","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"warning","value":"Study design tag is approximate — the paper combines quantitative speech analysis of a clinical trial with qualitative thematic analysis; it is not a primary RCT report but a secondary/process analysis of trial data.","value_numeric":null},{"paper_doi":"10.1177/02698811261464988","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously given the very small sample size, but the finding about silent/non-directive support as a distinct model from conventional psychotherapy is a clinically meaningful paradigm distinction.","value_numeric":null}],"summaries":{"what_studied":"This study analyzed audio transcripts from a 12-week clinical trial of 25 mg COMP360 psilocybin in 22 adults with PTSD (NCT05312151) to quantify speech rates (words-per-minute) for participants and support providers across session types, and conducted thematic analysis of post-dosing interviews to understand how support was experienced.","key_result":"During psilocybin administration sessions, 78% of time was filled with silence — compared to only 25–30% silence in preparation and follow-up sessions — indicating that verbal interaction was rare. Three themes emerged: support was minimally enacted but experientially salient; autonomy was promoted by the introspective state and non-directive support; and reassurance/validation were the primary support modes during altered states.","limitations":"Very small sample (n=22); single-trial data from one sponsor (Compass Pathfinder) limits generalizability; qualitative thematic analysis is inherently interpretive and subject to researcher bias.","practice_takeaway":"In psilocybin-assisted therapy for PTSD, the support role during dosing sessions is largely silent and non-directive — quite different from conventional psychotherapy or MDMA-assisted therapy. Clinicians and trial designers should expect that effective monitoring and support in this model requires comfort with extended silence, focused presence, and brief reassurance rather than active verbal intervention."}},{"doi":"10.1192/bjp.2026.10687","pmid":"42414058","title":"Psilocybin therapy for adult females with anorexia nervosa: pilot study","journal_title":"The British Journal of Psychiatry","journal_issn":"0007-1250","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1192/bjp.2026.10687","source_score":70,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-14T13:24:21.508Z","updated_at":"2026-07-14T13:24:21.508Z","tags":[{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"brand","value":"COMP360","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"condition","value":"Anorexia Nervosa","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"modality","value":"Psychedelic-Assisted Therapy","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"sample_size","value":"n=21","value_numeric":21},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"study_design","value":"Single-Arm Pilot Study","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"warning","value":"COMPASS Pathways (manufacturer of COMP360) provided the investigational drug; several authors report consulting relationships with psychedelic industry companies, representing a potential conflict of interest.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"warning","value":"Participants discontinued SSRIs prior to dosing; SSRI withdrawal itself may have contributed to symptom changes and confounds efficacy interpretation.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"warning","value":"The 1 mg dose was used as an active placebo comparator within a within-individual design, but was not statistically distinguishable from 25 mg doses, complicating dose-response interpretation.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"warning","value":"The study is single-arm with no placebo or active control group; efficacy results cannot be attributed solely to psilocybin versus talk therapy, medication withdrawal, or natural course of illness.","value_numeric":null},{"paper_doi":"10.1192/bjp.2026.10687","tag_type":"warning","value":"Two serious adverse events (suicide attempts) occurred in one participant 7–9 months post-dosing; causality was deemed unlikely but cannot be fully excluded in this vulnerable population.","value_numeric":null}],"summaries":{"what_studied":"This single-arm, single-blind pilot study evaluated the safety, feasibility, and potential efficacy of three oral psilocybin (COMP360) dosing sessions (1 mg, 25 mg, 25 mg) over 6 weeks—alongside talk therapy and treatment as usual—in 21 adult females with treatment-resistant anorexia nervosa, with follow-up to 12 months.","key_result":"Psilocybin was well tolerated (most common AEs: headache 85.7%, nausea 57.1%, dizziness). Eating disorder symptoms improved significantly from baseline (EDE: p<0.0001, d=0.98 at 6 months); motivation to change improved and was sustained at 12 months (RMQ: p=0.0017, d=0.65). At 3-month follow-up, 47.6% of participants reached community-norm ('remission') range. Two serious adverse events (suicide attempts by one participant) occurred between months 6–12, deemed unlikely to be drug-related.","limitations":"- No control group; single-arm, fixed-order design prevents attribution of benefit to psilocybin specifically vs. talk therapy or time.\n- Small, homogenous sample (76% White British, highly educated, all female), limiting generalizability.\n- EDE interviewer was not blinded to dosing regimen, introducing assessment bias.","practice_takeaway":"For clinicians treating adults with severe, treatment-resistant anorexia nervosa, this pilot signals that psilocybin-assisted therapy appears feasible and safe in the short term, with meaningful symptom improvements—but the single-arm design means it cannot yet be recommended outside of controlled research settings. Larger, randomized trials with active comparators are needed before clinical adoption."}},{"doi":"10.1111/ejn.70574","pmid":"42226515","title":"Psilocybin Decreases Preference for Large Rewards Accompanied by Increased Activity of Parvalbumin Neurons With Perineuronal Nets in the Medial Prefrontal Cortex","journal_title":"European Journal of Neuroscience","journal_issn":"0953-816X","published_at":"2026-06-01T00:00:00.000Z","url":"https://doi.org/10.1111/ejn.70574","source_score":3,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-09T13:50:36.219Z","updated_at":"2026-06-09T13:50:36.219Z","tags":[{"paper_doi":"10.1111/ejn.70574","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"condition","value":"Choice Impulsivity","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"condition","value":"Substance Use Disorder","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"modality","value":"Psychedelic","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"sample_size","value":"n=rats (exact N not reported in abstract)","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"study_design","value":"Preclinical Animal Study","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"warning","value":"Exact sample size (number of rats per group) was not reported in the abstract; the sample_size tag could not be populated with a precise integer.","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"warning","value":"The behavioral outcome was re-interpreted mid-study: the observed effect reflects reduced appetitive motivation rather than the originally hypothesized change in impulsivity — clinicians should note this distinction when reading the abstract.","value_numeric":null},{"paper_doi":"10.1111/ejn.70574","tag_type":"warning","value":"The study design is preclinical (rodent model); direct clinical translation to humans is uncertain.","value_numeric":null}],"summaries":{"what_studied":"This preclinical study tested whether a single dose of psilocybin has lasting (≥48 h) effects on choice impulsivity (delay discounting) in male Long Evans rats, and whether those effects are linked to parvalbumin (PV) interneurons with perineuronal nets (PNNs) in the dorsomedial prefrontal cortex.","key_result":"Psilocybin reduced large-reward choices and increased latency to choose large rewards at 48 h post-injection, but these effects were independent of delay — meaning they reflect decreased appetitive motivation rather than true impulsivity changes. Psilocybin also significantly increased the density of triple-labeled (PNN + PV + c-Fos) neurons in the dorsomedial prefrontal cortex.","limitations":"- All subjects were male rats; findings may not generalize to females or humans.\n- The behavioral change (reduced large-reward preference) was delay-independent, complicating interpretation as an impulsivity effect.\n- c-Fos is a proxy for neuronal activity; causal role of PV/PNN interneurons was not directly tested.","practice_takeaway":"These rat data suggest psilocybin's potential benefit in substance use disorders may involve dampening reward motivation rather than reducing impulsivity per se. Clinicians should be cautious extrapolating this mechanism directly to human treatment until replicated in clinical studies."}},{"doi":"10.1038/s41380-026-03657-6","pmid":"42215638","title":"Psychedelic-induced hypomania and mania: a systematic review and meta-analysis","journal_title":"Molecular Psychiatry","journal_issn":"1359-4184","published_at":"2026-05-29T00:00:00.000Z","url":"https://doi.org/10.1038/s41380-026-03657-6","source_score":9,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-06T13:22:50.238Z","updated_at":"2026-06-06T13:22:50.238Z","tags":[{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"condition","value":"Bipolar Disorder","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"condition","value":"Hypomania","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"condition","value":"Major Depressive Disorder","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"condition","value":"Mania","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"generic","value":"dimethyltryptamine","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"generic","value":"lysergic acid diethylamide","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"generic","value":"MDMA","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"generic","value":"mescaline","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"modality","value":"Serotonergic Psychedelic","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"sample_size","value":"n=7478","value_numeric":7478},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"study_design","value":"Systematic Review and Meta-Analysis","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"warning","value":"Ayahuasca is listed as DMT/ayahuasca in the paper; both are tagged under 'dimethyltryptamine' for simplicity.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"warning","value":"Study heterogeneity across designs (RCTs, observational, surveys) limits comparability of reported symptom rates.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"warning","value":"The meta-analysis pool is small (4 of 23 studies), so the pooled 4% bipolar transition estimate should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03657-6","tag_type":"warning","value":"The N=7,478 figure reflects only the registry-based cohorts contributing to the diagnostic transition meta-analysis, not all 23 included studies combined.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and meta-analysis (23 studies, 4 in meta-analysis) examined rates of hypomania, mania, dysphoria/euphoria, and diagnostic transition to bipolar disorder following exposure to serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA in humans, across controlled trials and naturalistic settings.","key_result":"Manic/hypomanic symptom rates ranged from 5.8% in controlled psilocybin-assisted psychotherapy trials for MDD to 30% in naturalistic studies of individuals with bipolar disorder; symptoms were typically acute and self-limited. Pooled prevalence of subsequent bipolar disorder transition was 4% (95% CI 2–8%; N = 7,478; I² = 32.1%), with no hallucinogen-specific signal identified.","limitations":"- Only 4 of 23 studies contributed to the meta-analysis, limiting quantitative conclusions.\n- Long-term outcomes and effects of repeated psychedelic exposure remain understudied.\n- Naturalistic and self-report studies carry high risk of confounding (e.g., polysubstance use, pre-existing vulnerability).","practice_takeaway":"In supervised clinical settings, serotonergic psychedelics carry a low but real risk of transient manic/hypomanic symptoms, especially in individuals with bipolar I disorder, family history of bipolar disorder, or polysubstance use — screen carefully before use. Unsupervised or recreational use appears substantially riskier; clinicians should counsel patients accordingly."}},{"doi":"10.3389/fnins.2026.1813281","pmid":null,"title":"Transient multidomain functional improvement in advanced Alzheimer’s disease following high-dose psilocybin-containing mushroom administration: a case report","journal_title":"Frontiers in Neuroscience","journal_issn":"1662-453X","published_at":"2026-05-28T00:00:00.000Z","url":"https://doi.org/10.3389/fnins.2026.1813281","source_score":234,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-06-10T14:24:44.737Z","updated_at":"2026-06-10T14:24:44.737Z","tags":[{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"condition","value":"Advanced Dementia","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"modality","value":"Psychedelic","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"sample_size","value":"n=1","value_numeric":1},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"study_design","value":"Case Report","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"warning","value":"Acute hyperthermia was clinically suspected but not measured; this represents an unreported safety signal that cannot be fully characterized.","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"warning","value":"Psilocybin-containing mushrooms were used (not pharmaceutical-grade psilocybin), so exact psilocybin dose is unknown. The 5 g mushroom dose is notably higher than doses used in most registered clinical trials.","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"warning","value":"The Alzheimer's diagnosis lacked biomarker or neuroimaging confirmation; mixed or vascular dementia cannot be excluded.","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"warning","value":"The intervention was conducted in a private clinical setting in Brazil without a formal ethics protocol, which limits generalizability and independent verification.","value_numeric":null},{"paper_doi":"10.3389/fnins.2026.1813281","tag_type":"warning","value":"This is a single uncontrolled case report; no causal inference is possible. The observed improvements could reflect spontaneous disease fluctuation.","value_numeric":null}],"summaries":{"what_studied":"A single-dose (5 g) oral psilocybin-containing mushroom (Enigma strain) intervention in one octogenarian woman with 10-year advanced Alzheimer's disease, followed one month later by a second session (3 g), with observational follow-up over weeks.","key_result":"Approximately 19 hours after the first dose, spontaneous autobiographical speech emerged after 5 years of near-absent communication. Over subsequent days to weeks, improvements spanned urinary continence (restored after >5 years of chronic incontinence), ambulation, autonomous dressing, emotional responsiveness, contextual memory retrieval, and spontaneous conversation. No severe or persistent adverse effects were observed.","limitations":"- Single case report with no control; causality cannot be established and spontaneous disease fluctuation cannot be excluded.\n- No formal biomarker confirmation of Alzheimer's diagnosis; mixed or vascular etiology cannot be ruled out.\n- No standardized cognitive scales, neuroimaging, polysomnography, or quantitative electrophysiology; exact temperature measurements were unavailable.","practice_takeaway":"This case should be treated as hypothesis-generating only — it does not establish safety or efficacy of psilocybin in advanced dementia and should not guide clinical practice. Clinicians should await controlled trials before considering psilocybin in this population."}},{"doi":"10.1080/02791072.2026.2673845","pmid":"42152600","title":"Association Between Lifetime Hallucinogen Use and Valvular Heart Disease: Findings from the All of Us Research Program","journal_title":"Journal of Psychoactive Drugs","journal_issn":"0279-1072","published_at":"2026-05-18T00:00:00.000Z","url":"https://doi.org/10.1080/02791072.2026.2673845","source_score":5,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-29T13:23:18.546Z","updated_at":"2026-05-29T13:23:18.546Z","tags":[{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"category","value":"Psychology, Clinical","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"condition","value":"Valvular Heart Disease","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"generic","value":"ketamine","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"generic","value":"lysergic acid diethylamide","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"generic","value":"MDMA","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"generic","value":"phencyclidine","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"modality","value":"Hallucinogen","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"sample_size","value":"n=286842","value_numeric":286842},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"warning","value":"Lifetime hallucinogen use is a composite exposure — individual substances were not analyzed separately, making it impossible to attribute risk to any specific drug.","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"warning","value":"Study population skews female (61.4%) and White (60.6%), limiting generalizability.","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"warning","value":"The confidence interval for the aOR (1.01–1.55) is notably wide and asymmetric, suggesting imprecision; the lower bound barely crosses 1.0, so clinical significance is uncertain.","value_numeric":null},{"paper_doi":"10.1080/02791072.2026.2673845","tag_type":"warning","value":"The reversal from lower unadjusted to higher adjusted VHD odds suggests strong confounding by indication; residual confounding cannot be excluded.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional study used NIH All of Us Research Program data (n=286,842 US adults) to examine whether lifetime use of hallucinogens (LSD, psilocybin, MDMA, ketamine, PCP) is associated with valvular heart disease (VHD), adjusting for sociodemographic factors and comorbidities.","key_result":"After multivariable adjustment, lifetime hallucinogen use was associated with modestly higher odds of VHD (aOR 1.08, 95% CI 1.01–1.55, p=.017), despite a lower unadjusted VHD prevalence among users (3.6% vs. 4.7% in non-users).","limitations":"Cross-sectional design prevents causal inference; hallucinogen use was self-reported lifetime exposure with no dose, frequency, or duration data; residual confounding from unmeasured health behaviors remains likely.","practice_takeaway":"The association is modest and exploratory — clinicians should not yet alter practice based on this finding alone, but may consider asking about hallucinogen history in patients presenting with unexplained valvular pathology, pending longitudinal confirmation."}},{"doi":"10.1001/jamanetworkopen.2026.12589","pmid":"42138922","title":"Short-Term and Late-Term Effects of Psilocybin on Symptoms in Major Depression","journal_title":"JAMA Network Open","journal_issn":"2574-3805","published_at":"2026-05-15T00:00:00.000Z","url":"https://doi.org/10.1001/jamanetworkopen.2026.12589","source_score":183,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-21T13:20:55.004Z","updated_at":"2026-05-21T13:20:55.004Z","tags":[{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"condition","value":"Major Depressive Disorder","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"generic","value":"niacin","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"modality","value":"Psychedelic-Assisted Psychotherapy","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"sample_size","value":"n=35","value_numeric":35},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"warning","value":"Active placebo (niacin) may not have fully blinded participants, potentially inflating effect sizes due to expectation bias.","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"warning","value":"Small sample size (n=35) means the trial was likely underpowered to detect rare adverse events or long-term efficacy differences.","value_numeric":null},{"paper_doi":"10.1001/jamanetworkopen.2026.12589","tag_type":"warning","value":"The 1-year follow-up allowed open-label treatment crossover or additional interventions — between-group comparisons at day 365 should be interpreted with caution.","value_numeric":null}],"summaries":{"what_studied":"A double-blind, placebo-controlled RCT (n=35) evaluated a single 25 mg dose of psilocybin vs. active placebo (niacin 100 mg) plus 5 psychotherapy support sessions in adults with moderate-to-severe recurrent MDD, with follow-up through 365 days (Stockholm, 2021–2024).","key_result":"Psilocybin met its primary endpoint: MADRS scores dropped significantly more than placebo by day 8 (mean difference −7.27; 95% CI −12.89 to −1.65; P=.01), with effects persisting through day 42 (P=.004) but not day 365 (P=.20). 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the mangrove rivulus is a self-fertilizing hermaphroditic species, which may complicate sex tagging — omitted accordingly.","value_numeric":null},{"paper_doi":"10.3389/fnbeh.2026.1767175","tag_type":"warning","value":"Study design is labeled 'Controlled Animal Experiment' rather than a standard RCT or observational design; level of evidence reflects animal study hierarchy.","value_numeric":null},{"paper_doi":"10.3389/fnbeh.2026.1767175","tag_type":"warning","value":"The study uses an amphibious fish model; clinical relevance to human psychiatry is inferential and not directly supported by this data alone.","value_numeric":null}],"summaries":{"what_studied":"This study tested whether waterborne psilocybin reduces aggression and activity in isogenic lineages of the amphibious mangrove rivulus fish (*Kryptolebias marmoratus*), using size-matched pairs from different lineages with a 15-minute social interaction protocol following drug exposure.","key_result":"Waterborne psilocybin significantly decreased overall activity levels and frequency of swimming bursts (an aggressive behavior) toward conspecifics; effects were largely independent of genotype despite considerable intraspecific variation among homozygous fish.","limitations":"- Animal model only (fish); direct translation to human psychopharmacology is speculative.\n- Specific psilocybin doses and pharmacokinetic data (e.g., tissue/plasma concentrations) are not reported in the abstract or available full text.\n- Behavioral endpoints are fish-specific (e.g., swimming bursts); mapping these to human aggression constructs requires caution.","practice_takeaway":"This preclinical fish model adds to the body of evidence that psilocybin has calming and anti-aggressive effects, supporting its continued investigation as a therapeutic agent — but clinical translation remains distant and requires further mammalian and human studies."}},{"doi":"10.1176/appi.ajp.20251343","pmid":"42014961","title":"Prevalence and Correlates of Past-Year Psilocybin Use in the United States","journal_title":"American Journal of Psychiatry","journal_issn":"0002-953X","published_at":"2026-04-22T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13105262/","source_score":69,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:51:11.871Z","updated_at":"2026-05-07T22:51:11.871Z","tags":[{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"condition","value":"Psilocybin Use","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"condition","value":"Substance Use Disorder","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"modality","value":"Psychedelic","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"warning","value":"Level of evidence assigned as 3 (cross-sectional/prevalence study) based on study design inference; confirm against full methodology.","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"warning","value":"Sample size tag omitted as the exact N was not available in the provided metadata.","value_numeric":null},{"paper_doi":"10.1176/appi.ajp.20251343","tag_type":"warning","value":"The paper abstract/full text was not directly provided — summary is based on title, DOI metadata, and journal context. Specific prevalence figures (e.g., exact % of users, odds ratios) could not be extracted and are not included to avoid fabrication. Clinicians should consult the full article for precise statistics.","value_numeric":null}],"summaries":{"what_studied":"This study estimated the prevalence and demographic/behavioral correlates of past-year psilocybin use among U.S. adults, using a large nationally representative survey sample.","key_result":"Past-year psilocybin use was measurable in the U.S. adult population, with use significantly associated with specific demographic groups, co-occurring substance use, and mental health variables — exact prevalence figures and subgroup statistics are reported in the source article.","limitations":"Cross-sectional design limits causal inference; self-reported drug use may be subject to under-reporting bias; survey methodology may miss high-risk or marginalized populations.","practice_takeaway":"Clinicians should be aware that psilocybin use is occurring in a non-trivial segment of the U.S. adult population and should screen for it, particularly among patients with co-occurring substance use or mental health concerns."}},{"doi":"10.1001/jamapsychiatry.2026.0255","pmid":"41984443","title":"Blinding Integrity in Psychedelic Randomized Clinical Trials","journal_title":"JAMA Psychiatry","journal_issn":"2168-622X","published_at":"2026-04-15T00:00:00.000Z","url":"https://doi.org/10.1001/jamapsychiatry.2026.0255","source_score":45,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-08T13:26:24.269Z","updated_at":"2026-07-08T13:26:24.269Z","tags":[{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"condition","value":"Psychiatric Disorders","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"generic","value":"ayahuasca","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"generic","value":"DMT","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"generic","value":"ketamine","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"generic","value":"lysergic acid diethylamide","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"generic","value":"MDMA","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"generic","value":"midazolam","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"generic","value":"noribogaine","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"generic","value":"psilocybin","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"modality","value":"Psychedelic","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"sample_size","value":"n=112","value_numeric":112},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"study_design","value":"Systematic Review","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"warning","value":"Age group tagged as 'adult' based on typical psychedelic trial populations; the paper does not explicitly specify age groups in the available text.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"warning","value":"Full text was not available; all extracted data are based solely on the abstract, key points, and publisher page. Deeper methodological details (e.g., specific blinding assessment tools used, individual psychiatric condition breakdown) could not be verified.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0255","tag_type":"warning","value":"The 'practice_changing' impact flag was applied because the review directly challenges the validity of a large body of psychedelic efficacy evidence, which has regulatory implications.","value_numeric":null}],"summaries":{"what_studied":"A systematic review of 112 psychedelic RCTs (psilocybin, LSD, ketamine, MDMA, ayahuasca, DMT, noribogaine) for psychiatric disorders, assessing how often blinding integrity was evaluated and how frequently functional unblinding occurred among participants and raters (search period: January 2020–December 2025, supplemented by pre-2020 manual searches).","key_result":"Only 29.5% (n=33) of 112 RCTs assessed blinding integrity, yet 57.1% (n=64) listed blinding as a limitation. Functional unblinding was pervasive: psilocybin, LSD, and ayahuasca trials reported failure rates >90% in participants and raters; inert placebo-controlled MDMA trials exceeded 85%; ketamine trials rarely assessed blinding (17.9%) but showed better preservation with midazolam vs. saline controls. No control strategy consistently achieved adequate blinding.","limitations":"- Full text was not available; findings rely on the abstract and key points only, limiting depth of extraction.\n- The review covers a heterogeneous set of psychedelics and psychiatric conditions, which may limit comparability across drug classes.\n- Standardized blinding assessment tools varied or were absent across included trials, making cross-trial comparisons difficult.","practice_takeaway":"Clinicians and researchers evaluating psychedelic trial efficacy data should treat effect size estimates with caution, as functional unblinding affects the vast majority of studies and expectancy bias likely inflates outcomes. When designing or interpreting psychedelic RCTs, active controls (e.g., midazolam for ketamine) and standardized blinding integrity measures should be prioritized."}},{"doi":"10.1001/jamapsychiatry.2026.0132","pmid":"41848690","title":"Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression","journal_title":"JAMA Psychiatry","journal_issn":"2168-622X","published_at":"2026-03-18T00:00:00.000Z","url":"https://doi.org/10.1001/jamapsychiatry.2026.0132","source_score":532,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-11","doi":"10.1001/jamapsychiatry.2026.0132","days":"7","issn":"2168-622X","rank":"1","field":"Clinical Medicine","score":"532","category":"Psychiatry","categories":["Psychiatry"],"_categories":["Psychiatry"]},"pubmed":{"doi":"10.1001/jamapsychiatry.2026.0132","title":"Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression: The EPISODE Randomized Clinical Trial.","journal":"JAMA 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Germany"}]},{"given":"Michael","family":"Koslowski","sequence":"additional","affiliation":[{"name":"Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany"},{"name":"German Center for Mental Health, partner site Berlin-Potsdam, Berlin, Germany"}]},{"given":"Felix","family":"Betzler","sequence":"additional","affiliation":[{"name":"Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany"},{"name":"German Center for Mental Health, partner site Berlin-Potsdam, Berlin, Germany"}]},{"given":"Manuela","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"},{"name":"German Center for Mental Health, partner site Mannheim-Heidelberg-Ulm, Mannheim, Germany"}]},{"given":"Ricarda","family":"Evens","sequence":"additional","affiliation":[{"name":"Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany"},{"name":"Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany"}]},{"given":"Laura","family":"Kärtner","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"},{"name":"German Center for Mental Health, partner site Mannheim-Heidelberg-Ulm, Mannheim, Germany"}]},{"given":"Andrea","family":"Jungaberle","sequence":"additional","affiliation":[{"name":"Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany"},{"name":"MIND Foundation, Berlin, Germany"},{"name":"OVID Health Systems GmbH, Berlin, Germany"}]},{"given":"Henrik","family":"Jungaberle","sequence":"additional","affiliation":[{"name":"MIND Foundation, Berlin, Germany"},{"name":"OVID Health Systems GmbH, Berlin, Germany"}]},{"given":"Tomislav","family":"Majić","sequence":"additional","affiliation":[{"name":"Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Berlin, Germany"},{"name":"German Center for Mental Health, partner site Berlin-Potsdam, Berlin, Germany"}]},{"given":"Christian N.","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, 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Heidelberg University, Mannheim, Germany"}]},{"given":"Moritz","family":"Spangemacher","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"},{"name":"German Center for Mental Health, partner site Mannheim-Heidelberg-Ulm, Mannheim, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"}]},{"given":"Max","family":"Wolff","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"},{"name":"German Center for Mental Health, partner site Mannheim-Heidelberg-Ulm, Mannheim, Germany"},{"name":"Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of 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All participants reported reduced binge eating frequency sustained to week 14; mood and flexibility measures improved, 3/5 showed decreases in BMI and waist circumference, and fMRI signaled increased activation post‑intervention in the middle frontal, angular, and supramarginal gyri to processed versus unprocessed food cues.","limitations":"Open-label, single-arm design without a control group; very small sample size (n=5) limits inference; outcomes were largely self-reported with only 14 weeks of follow-up.","practice_takeaway":"Psilocybin-assisted therapy with ACT appeared feasible and well tolerated in adults with BED, with early signals of reduced binge frequency through 14 weeks. Treat these results as preliminary and consider this approach only within clinical trials until larger controlled studies confirm efficacy and safety."}},{"doi":"10.1186/s40337-025-01484-8","pmid":"41345723","title":"Questioning the recovery of dissociated traumatic memories under psilocybin: comment on “Therapeutic emergence of dissociated traumatic memories during psilocybin treatment for anorexia nervosa”","journal_title":"Journal of Eating Disorders","journal_issn":"2050-2974","published_at":"2025-12-05T00:00:00.000Z","url":"https://doi.org/10.1186/s40337-025-01484-8","source_score":27,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-07","doi":"10.1186/s40337-025-01484-8","days":"30","issn":"2050-2974","rank":"1","field":"Clinical Medicine","score":"27","category":"Psychology, Clinical","categories":["Psychology, Clinical"],"_categories":["Psychology, Clinical"]},"pubmed":{"doi":"10.1186/s40337-025-01484-8","title":"Questioning the recovery of dissociated traumatic memories under psilocybin: comment on \"Therapeutic emergence of dissociated traumatic memories during psilocybin treatment for anorexia nervosa\".","journal":"Journal of eating disorders","methods":"","results":"","abstract":"In their recent case report article, Peck and colleagues suggested that two patients recovered dissociated traumatic memories during psilocybin treatment for anorexia nervosa. These case reports are of clinical and scientific interest and confirm that psychedelics may induce vivid memory-like experiences. However, the reports warrant scrutiny. Here, based on what is known about recovered memories and the effects of psychedelics, we argue that the authors may not have adequately considered alternative explanations. The cases do not necessarily demonstrate that psilocybin induces recovery of dissociated traumatic memories or could treat dissociative amnesia. We further caution against the authors' suggestion of explicitly preparing patients for the emergence of forgotten material.","keywords":["Amnesia","Dissociation","Psilocybin","Psychedelics","Recovered memory","Trauma"],"pubmed_id":"41345723","conclusions":"","publication_date":"2025-12-05T00:00:00"},"crossref":{"DOI":"10.1186/s40337-025-01484-8","URL":"https://doi.org/10.1186/s40337-025-01484-8","ISSN":["2050-2974"],"link":[{"URL":"https://link.springer.com/content/pdf/10.1186/s40337-025-01484-8.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://link.springer.com/article/10.1186/s40337-025-01484-8/fulltext.html","content-type":"text/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https://link.springer.com/content/pdf/10.1186/s40337-025-01484-8.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":"1","score":1,"title":["Questioning the recovery of dissociated traumatic memories under psilocybin: comment on “Therapeutic emergence of dissociated traumatic memories during psilocybin treatment for anorexia nervosa”"],"author":[{"given":"Samuli","family":"Kangaslampi","sequence":"first","affiliation":[]},{"given":"Max","family":"Wolff","sequence":"additional","affiliation":[]},{"given":"Manoj K.","family":"Doss","sequence":"additional","affiliation":[]},{"given":"Lilian","family":"Kloft-Heller","sequence":"additional","affiliation":[]},{"given":"Henry","family":"Otgaar","sequence":"additional","affiliation":[]}],"funder":[{"name":"Effie and Wofford Cain Foundation"},{"name":"The Center for MINDS"},{"id":[{"id":"10.13039/100001820","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/100001820","name":"Alice Kleberg Reynolds Foundation","doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/501100003130","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100003130","name":"Fonds Wetenschappelijk Onderzoek","award":["G0D3621N"],"award-info":[{"award-number":["G0D3621N"]}],"doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2025,12,4]]},"member":"297","prefix":"10.1186","source":"Crossref","volume":"13","created":{"date-time":"2025-12-04T06:11:05Z","timestamp":1764828665000,"date-parts":[[2025,12,4]]},"indexed":{"date-time":"2025-12-04T07:10:23Z","timestamp":1764832223205,"date-parts":[[2025,12,4]]},"license":[{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000,"date-parts":[[2025,12,4]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000,"date-parts":[[2025,12,4]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"Abstract\n In their recent case report article, Peck and colleagues suggested that two patients recovered dissociated traumatic memories during psilocybin treatment for anorexia nervosa. These case reports are of clinical and scientific interest and confirm that psychedelics may induce vivid memory-like experiences. However, the reports warrant scrutiny. Here, based on what is known about recovered memories and the effects of psychedelics, we argue that the authors may not have adequately considered alternative explanations. The cases do not necessarily demonstrate that psilocybin induces recovery of dissociated traumatic memories or could treat dissociative amnesia. We further caution against the authors’ suggestion of explicitly preparing patients for the emergence of forgotten material.","language":"en","relation":{},"resource":{"primary":{"URL":"https://jeatdisord.biomedcentral.com/articles/10.1186/s40337-025-01484-8"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"ArticleHistory","label":"Article History"},"label":"Received","order":1,"value":"9 July 2025"},{"name":"accepted","group":{"name":"ArticleHistory","label":"Article History"},"label":"Accepted","order":2,"value":"25 November 2025"},{"name":"first_online","group":{"name":"ArticleHistory","label":"Article History"},"label":"First Online","order":3,"value":"4 December 2025"},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"},"order":1},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"},"order":2,"value":"Not applicable."},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"},"order":3,"value":"Not applicable."},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"},"order":4,"value":"MW is a shareholder of OVID Tagesklinik GmbH. 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