JAMA Psychiatry
November 4, 2020
Mary P Cosimano, Alan K. Davis, Frederick S. Barrett et al.
1,269 citations
Two doses of psilocybin (20 and 30 mg per 70 kg) combined with supportive psychotherapy produced large, rapid antidepressant effects in adults with major depressive disorder who were not taking other antidepressants. In a randomized waiting list-controlled trial with 24 completers, depression scores on the GRID-Hamilton scale dropped from a mean of 22.8 at baseline to 8.0 one week after the second session, compared with 23.8 at the same time point in the delayed-treatment group. Seventy-one percent of participants showed a clinically significant response at week 1, and 58% met remission criteria. Effects persisted through the four-week follow-up.
JAMA Psychiatry
June 5, 2019
Ella J. Daly, Madhukar H. Trivedi, Adam Janik et al.
766 citations
For adults with treatment-resistant depression who achieved stable remission or response after 16 weeks of esketamine nasal spray plus an oral antidepressant, continuing esketamine plus the antidepressant delayed relapse significantly more than switching to placebo plus the antidepressant. Among those in stable remission, 26.7% relapsed on esketamine versus 45.3% on placebo, a 51% reduction in relapse risk. Among stable responders, 25.8% relapsed on esketamine versus 57.6% on placebo, a 70% reduction. Common side effects of esketamine included transient taste disturbance, vertigo, dissociation, drowsiness, and dizziness.
JAMA Psychiatry
December 27, 2017
Ella J. Daly, Jaskaran B. Singh, Maggie Fedgchin et al.
708 citations
In adults with treatment-resistant depression, intranasal esketamine at doses of 28 mg, 56 mg, and 84 mg produced a rapid, dose-related reduction in depressive symptoms compared to placebo, as measured by the Montgomery-Åsberg Depression Rating Scale. The improvement appeared to persist for more than two months even when dosing frequency was reduced. Adverse events leading to discontinuation occurred in 5% of esketamine-treated participants during the double-blind phase and in 2% during the open-label phase, with no such events in the placebo group.
JAMA Psychiatry
August 24, 2022
Michael P. Bogenschutz, Stephen Ross, Snehal Bhatt et al.
668 citations
Two doses of psilocybin, given alongside psychotherapy, substantially reduced heavy drinking in people with alcohol use disorder compared to an active placebo (diphenhydramine) plus psychotherapy. Over 32 weeks, heavy drinking days averaged 9.7% in the psilocybin group versus 23.6% in the placebo group—a mean difference of 13.9 percentage points. Daily alcohol consumption was also lower with psilocybin. No serious adverse events occurred in the psilocybin group. The findings support further research into psilocybin-assisted treatment for alcohol use disorder.
JAMA Psychiatry
April 16, 2014
Adriana Feder, Michael K. Parides, James W. Murrough et al.
618 citations
A single intravenous dose of ketamine (0.5 mg/kg) rapidly reduced posttraumatic stress disorder (PTSD) symptom severity more than the active placebo midazolam in patients with chronic PTSD. Twenty-four hours after infusion, the ketamine group showed a mean reduction of 12.7 points on the Impact of Event Scale-Revised compared to midazolam. Ketamine also lessened comorbid depressive symptoms and improved overall clinical presentation. The treatment was generally well tolerated without persistent dissociative symptoms. These results suggest ketamine may offer a novel pharmacologic approach for chronic PTSD, though replication is needed.
JAMA Psychiatry
March 1, 2017
Gerard Sanacora, Mark A. Frye, William M. Mcdonald et al.
577 citations
Ketamine can produce rapid and robust antidepressant effects in patients with mood and anxiety disorders that were previously resistant to treatment. However, existing studies have relatively small sample sizes, lack longer-term data on efficacy, and provide limited data on safety. Despite these limitations, ketamine is increasingly used off-label for mood and other psychiatric disorders. This review and consensus statement provides an overview of the data, highlights limitations, and offers suggestions to facilitate evidence-based clinical decision-making and patient safety.
JAMA Psychiatry
February 6, 2013
Jonathan Posner, David J. Hellerstein, Inbal Gat et al.
275 citations
People with dysthymic disorder (DD) show greater coherence of neural activity within the brain's default mode network (DMN) compared with healthy controls, similar to abnormalities seen in major depressive disorder. In a 10-week double-blind, placebo-controlled trial of duloxetine, treatment with duloxetine normalized DMN connectivity, while placebo did not. The findings suggest increased DMN connectivity may be important in the pathophysiology of depressive illness, and its normalization may be a causal pathway through which antidepressants reduce depression.
JAMA Psychiatry
February 1, 2021
David Nutt, Robin Carhart-Harris
233 citations
No Summary
JAMA Psychiatry
December 7, 2022
Joshua S. Siegel, James E. Daily, Demetrius A. Perry et al.
168 citations
Between 2019 and 2022, 25 U.S. states considered 74 bills related to psychedelic drugs, with 10 enacted and 32 still active. The number of bills introduced each year rose from 5 in 2019 to 36 in 2022. Most bills (90%) specified psilocybin, and 58% proposed decriminalization, though few included medical oversight or licensure requirements. Early legislative efforts occurred in liberal states, but the partisan gap has narrowed, suggesting reform is becoming bipartisan. An analytic model based on marijuana legalization projects that a majority of states will legalize psychedelics by 2034 to 2037.
JAMA Psychiatry
March 29, 2023
Sarah Mcnamee, Neşe Devenot, Meaghan Buisson
167 citations
Serious adverse events in psychedelic-assisted therapy trials can arise from interactions between therapists and patients. This Viewpoint discusses such events, highlighting the importance of therapeutic relationship dynamics in ensuring participant safety.
JAMA Psychiatry
October 1, 2022
David B. Yaden, James B. Potash, Roland R. Griffiths
153 citations
Public perception of psychedelics has swung from extreme stigma to uncritical enthusiasm, creating obstacles for clinical application. This viewpoint argues that both poles are problematic and advocates for continued scientific study while encouraging critical examination of claims not supported by evidence. The authors call for a balanced approach that neither dismisses therapeutic potential nor overpromises benefits, emphasizing the need for rigorous research to guide responsible clinical integration.
JAMA Psychiatry
September 4, 2024
Marianna Graziosi, Jared T. Hinkle, Sandeep M. Nayak et al.
126 citations
Classic psychedelics such as LSD and psilocybin are generally well tolerated in clinical or research settings, though serious adverse events do occur. In a systematic review and meta-analysis of 214 studies, serious adverse events were reported for no healthy participants and for about 4% of participants with preexisting neuropsychiatric disorders, including worsening depression, suicidal behavior, psychosis, and convulsive episodes. Nonserious adverse events requiring medical intervention, such as paranoia and headache, were rare. In contemporary research, no deaths by suicide, persistent psychotic disorders, or hallucinogen persisting perception disorders were reported after high-dose psychedelic administration. However, the quality of adverse event monitoring and reporting varied significantly across studies.
JAMA Psychiatry
May 1, 2021
David B. Yaden, Mary E. Yaden, Roland R. Griffiths
102 citations
No Summary
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.
JAMA Psychiatry
June 1, 2023
Vikas Menon, Natarajan Varadharajan, Abdul Faheem et al.
50 citations
Electroconvulsive therapy (ECT) appears more effective than ketamine for treating major depressive episodes in adults, though the evidence is limited by small studies. A meta-analysis of five randomized trials (141 ketamine patients, 137 ECT patients) found ECT produced significantly higher response and remission rates one week after treatment. ECT was 27% more likely to achieve response and 43% more likely to achieve remission than ketamine. In methodologically stronger trials, ECT showed a moderate advantage over ketamine on depression rating scales. No significant differences emerged between treatments for number of sessions needed or cognitive side effects. The authors caution that conclusions are tempered by the small number and size of existing trials.
JAMA Psychiatry
June 1, 2023
Jacob S. Aday, Robin L. Carhart-Harris, Joshua D. Woolley
48 citations
The abstract discusses emerging challenges for psychedelic therapy, highlighting obstacles such as regulatory hurdles, accessibility issues, equity concerns, and the need for practitioner training. It underscores difficulties in integrating psychedelic treatments into mainstream healthcare, including governance, legal frameworks, and developing accessible and equitable treatment models. The text suggests that responsible integration requires addressing these barriers to ensure safe and effective mental health care.
JAMA Psychiatry
April 10, 2024
Mason Marks, Rebecca Weintraub Brendel, Carmel Shachar et al.
46 citations
As interest in psychedelics for mental health treatment grows, legal reforms and regulatory approvals are advancing faster than standards for informed consent. Psychedelics pose unique challenges for consent, including perceptual disturbances, personality changes, altered metaphysical beliefs, risks of abuse or coercion, and the role of touch and data collection. Current consent documents in clinical trials often overlook these elements. Seven essential components for psychedelic informed consent are identified, and sample language and procedures are proposed to address the gap.
JAMA Psychiatry
May 11, 2022
Sina Nikayin, Taeho Greg Rhee, Maria Elena Cunningham et al.
43 citations
In a clinical setting, patients treated with intravenous ketamine or intranasal esketamine showed similar trajectories of depression severity over time, suggesting both treatments are comparably effective for depression.
JAMA Psychiatry
March 13, 2024
Otto Simonsson, Miriam A. Mosing, Walter Osika et al.
41 citations
Among 16,255 Swedish adolescents, 541 reported past psychedelic use, and 99% of those also used other drugs. After adjusting for other drug use, psychedelic use was associated with fewer psychotic symptoms. However, the link between psychedelic use and manic symptoms depended on genetic vulnerability: adolescents with higher genetic risk for schizophrenia or bipolar I disorder showed more manic symptoms after psychedelic use. The authors urge caution due to study limitations.
JAMA Psychiatry
January 3, 2024
Samuel T. Wilkinson, Joseph J. Palamar, Gerard Sanacora
41 citations
Ketamine's use is expanding both as a medical therapeutic and as a recreational substance, raising concerns about potential risks. The authors discuss the need for increased research and surveillance to better understand and manage these dual trends.
JAMA Psychiatry
June 26, 2019
Boris D. Heifets, Robert C. Malenka
28 citations
Methylenedioxy-methamphetamine (MDMA) and psilocybin may offer therapeutic benefits for mental health conditions, but their approval for treatment would require establishing appropriate mental health care infrastructures. This includes trained therapists, treatment protocols, and regulatory frameworks to ensure safe and effective use. The authors outline the necessary preparations for integrating these substances into clinical practice.
JAMA Psychiatry
April 27, 2022
Mazdak M. Bradberry, Natalie Gukasyan, Charles L. Raison
20 citations
No Summary
JAMA Psychiatry
April 16, 2025
Samuel T. Wilkinson, Gerard Sanacora
14 citations
The US Food and Drug Administration rejected MDMA as a treatment for posttraumatic stress disorder, citing concerns about lack of blinding and integrity issues in the clinical trials that had been conducted. This viewpoint examines the potential justifications for that decision.
JAMA Psychiatry
May 31, 2023
Abigail Calder, Gregor Hasler
14 citations
Optimizing safety for patients and therapists during psychedelic-assisted psychotherapy requires specific methods. The Viewpoint proposes approaches to enhance safety in this therapeutic context.
JAMA Psychiatry
March 18, 2026
Zachary J. Williams, Hannah Barnett, Balázs Szigeti
10 citations
In trials for major depression, psychedelic-assisted therapy (PAT) was no more effective than open-label traditional antidepressants (TADs) such as SSRIs and SNRIs. Across 8 PAT trials (249 patients) and 16 open-label TAD trials (7921 patients), the estimated difference in symptom improvement was 0.3 favoring TADs, a statistically non-significant result. Open-label TADs outperformed blinded TAD treatment, but PAT showed no such difference, confirming that PAT trials are effectively always open label. These findings challenge overly optimistic claims about PAT and underscore the importance of maintaining blinding integrity in clinical research.