JAMA Psychiatry
December 6, 2023
Tammy Miller, Jeffrey LaPratt, Kimberly Swartz et al.
101 citations
A single 25 mg dose of synthetic psilocybin combined with psychotherapy produced rapid and sustained reductions in depression symptoms in people with bipolar II disorder who had not responded to at least two prior treatments. Fifteen participants completed the trial; depression scores on the Montgomery-Åsberg Depression Rating Scale dropped by an average of 24 points three weeks after dosing, and 12 of 15 met both response and remission criteria by the 12-week endpoint. Mania and suicide risk scores did not increase. The open-label design limits certainty, but the results suggest psilocybin may be safe and effective for bipolar II depression.
American Journal of Psychiatry
January 1, 2025
Scott T Aaronson, Andrew van der Vaart, Tammy Miller et al.
31 citations
In an open-label study, psilocybin appears effective and safe for people with severe treatment-resistant depression, supporting further research into psychedelics for this group, including how post-traumatic stress disorder may affect outcomes.
Clinical Psychology & Psychotherapy
July 2, 2023
Aileen Kucsera, Trisha Suppes, Nancy A. Haug
27 citations
Mental health professionals in California report limited knowledge about the risks and benefits of psychedelic use, with average knowledge scores of 4.7 and 5.4 on a 10-point scale. 45% feel inadequately informed to counsel patients on psychedelic use. Despite this, 97% support additional research, 91% approve of medical use, and 89% believe in therapeutic benefits. 73% discuss psychedelics with patients, but 49% are uncomfortable addressing their effects. Greater knowledge correlates with more favorable attitudes and clinical practices. The findings indicate a need for better provider education on psychedelics.
Journal of affective disorders
January 15, 2025
Sara Ellis, Catherine Bostian, Wendy Feng et al.
23 citations
In a small, uncontrolled trial, 15 veterans with severe treatment-resistant depression received a single 25 mg dose of psilocybin. At three weeks, 60% met criteria for response and 53% for remission. By twelve weeks, 47% maintained response and 40% remission. Co-occurring PTSD did not affect outcomes, and the intensity of the psychedelic experience did not correlate with depression improvement. Four participants who needed to restart antidepressants were counted as non-responders from that point. No unexpected adverse events occurred. The authors note limitations including the small sample and lack of a control group, and call for further study.
The American journal of psychiatry
January 1, 2025
Roger S McIntyre, Angela T H Kwan, Rodrigo B Mansur et al.
23 citations
Psychedelics show promise for treating difficult-to-treat psychiatric disorders like major depressive disorder, treatment-resistant depression, and posttraumatic stress disorder, with preliminary evidence also supporting efficacy in tobacco and alcohol use disorders. However, concerns exist about the interpretability and translatability of study results due to insufficiently characterized short- and long-term safety, abuse liability, and the essentiality of the psychedelic experience and psychological support. This overview reviews methodological aspects affecting inferences and interpretation of extant psychedelic studies and provides guidance for future research and development critical to study interpretation and clinical implementation.
JAMA network open
April 1, 2025
Xue Zhang, Laura M Hack, Claire Bertrand et al.
10 citations
In a double-blind, placebo-controlled trial, 16 adults with subthreshold PTSD symptoms and early life trauma but no current psychiatric disorders were given 120 mg of MDMA or placebo. Participants were split into two groups based on baseline brain activity in the amygdala in response to nonconscious threat cues: those with high amygdala reactivity (NTNA+) and those with low reactivity (NTNA-). MDMA, compared with placebo, reduced activity in the amygdala and subgenual anterior cingulate cortex (sgACC), increased connectivity between the sgACC and amygdala, and increased liking of threatening facial expressions, but only in the NTNA+ subgroup. These findings suggest that baseline neural circuit profiles can identify who may benefit most from MDMA therapy and point to possible biomarkers for personalized treatment.
CNS spectrums
December 1, 2024
Mathieu Fradet, Carlton M Kelly, Anna J Donnelly et al.
10 citations
Psilocybin therapy shows promise as a new treatment for depression and other mental health disorders. The chapter reviews recent data on its safety and efficacy, describes how the therapy is delivered and its subjective effects, and outlines current understanding of psilocybin's pharmacology and neurobiological effects. Other psychedelic substances with therapeutic potential are also briefly discussed.
EClinicalMedicine
September 24, 2025
Megan Hosein, Matthew J. Reid, Sarah A. Walser et al.
5 citations
Psilocybin and other psychedelics show promise as a new class of psychiatric treatments, but their rapid development risks outpacing the guidelines and infrastructure needed for safe clinical integration. A consensus statement from the US National Network of Depression Centers (NNDC) Task Group on Psychedelics and Related Compounds, comprising psychiatrists, psychologists, neuroscientists, psychedelic researchers, and healthcare consultants, recognizes psilocybin's therapeutic potential while emphasizing the need for further research. Key gaps include understanding therapeutic dosage, efficacy across diverse populations, and long-term safety. The authors call for diversified funding, collaborative research, standardized provider training, and careful ethical consideration. They advocate for a balanced approach prioritizing rigorous science and equitable access, noting the single-country focus limits international generalizability.
Journal of affective disorders
June 9, 2025
Sara Ellis, Catherine Bostian, Anna Donnelly et al.
3 citations
Among veterans with severe treatment-resistant depression, a single 25 mg dose of psilocybin produced significant reductions in depression scores that were sustained for up to 12 months, though antidepressant effects began to wane after 6 months and more substantially after 9 months. At 12 months, 40% of 10 participants maintained a response (≥50% reduction in MADRS) and 30% maintained remission (MADRS ≤10). The study was a small, open-label pilot without a control group, so the findings suggest but do not demonstrate lasting benefit.
bioRxiv Preprint Server
September 20, 2021
Laura M. Hack, Katherine G. Warthen, Xue Zhang et al.
2 citations
preprint
Ketamine, a drug used for depression and anesthesia, causes dose-dependent increases in dissociation and intoxication, reduces emotional insensitivity, and raises stress as measured by cortisol. It alters brain connectivity, particularly between reward and negative affect circuits and thalamic sub-regions. Increased coupling between the amygdala and anteroventral thalamus correlates with greater dissociation and intoxication, while decreased coupling of anteromedial and posterior parietal thalamus correlates with increased sensory reward responsiveness. Drug-altered connectivity involving the nucleus accumbens and thalamic sub-regions shows negative associations with anxiety. These findings help disentangle the brain states underlying ketamine's acute effects, informing its therapeutic use and abuse risk.
Journal of affective disorders
November 1, 2026
Carlton M Kelly, Mathieu Fradet, Catherine M Bostian et al.
A single 25-mg dose of psilocybin with psychological support was associated with sustained improvements in anxiety, quality of life, functioning, and PTSD symptoms in 15 veterans with treatment-resistant depression. Anxiety scores dropped 59% from baseline at three weeks and remained lower through 12 months. Quality of life increased 24% and functional impairment decreased 46% at three weeks, though these effects were no longer statistically significant after accounting for concurrent improvements in depression. PTSD symptom reductions were observed at all timepoints. Acute subjective experiences did not correlate with treatment response. The study is limited by its small sample and open-label design.
The Journal of clinical psychiatry
May 13, 2026
Andrew van der Vaart, Jeffrey LaPratt, Kimberly Swartz et al.
A single 25-mg dose of a synthetic psilocybin formulation, combined with psychological support, rapidly and durably reduced chronic suicidal ideation and depressive symptoms in 20 adults with major depressive disorder who had not responded to at least two prior antidepressant treatments. Suicidal ideation scores dropped significantly by week 1, remained reduced at week 3 (the primary endpoint), and were still lower at week 12, when 70% of participants had minimal or no suicidal ideation. Depressive symptoms also improved substantially. No serious adverse events occurred. The findings are preliminary and require confirmation in larger randomized trials.
Journal of psychopharmacology (Oxford, England)
February 5, 2026
Benjamin R Lewis, Matthew J Reid, Andrew M Novick et al.
Clinical trials of classical psychedelics like psilocybin for mental health conditions face unique challenges that may persist if these treatments enter clinical practice. Four categories of challenges with trial participants are identified: treatment nonresponse, expectancy effects and functional unblinding, post-session psychological difficulties, and contagion effects. Management strategies for study teams to mitigate these risks are described. The National Network of Depression Centers and similar organizations can guide best practices to responsibly advance this promising field.
CNS Spectrums
January 1, 2025
Mathieu Fradet, Cecelia Kelly, Anna J. Donnelly et al.
No Summary
Journal of clinical psychopharmacology
John L Havlik, Sayana Isaac, Pralahad Raman et al.
As of late 2024, 181 ongoing clinical trials of psychogenic substances for psychiatric disorders are registered on ClinicalTrials.gov. Most are in phase 2 (51.4%) or phase 1 (18.2%), with psilocybin (35.4%) and ketamine (33.7%) the most studied compounds. Trials concentrate at a few leading academic institutions. Over 81% list their funding source as "other," and 86% of those are sponsored by universities or university-affiliated institutions. Blinding is not reported in 38.7% of trials. Major depressive disorder (51.9%), posttraumatic stress disorder (21.0%), and alcohol use disorder (11.6%) are the primary conditions targeted. The lack of clear funding disclosure indicates a need for greater transparency.