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
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
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
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
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
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
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
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
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
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
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
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
November 5, 2025
Kent E. Hutchison, Judith Hooper, Hollis C. Karoly
10 citations
Psilocybin mushroom use has sharply increased in the US, particularly among adults aged 19 to 50 years, with more than 7 million individuals reporting use in the past year. This trend has coincided with a substantial increase in poison control center calls related to psychedelics. Testing data from decriminalized regions indicate more than 20-fold variability in psilocybin potency and inconsistent levels of minor tryptamines across mushroom strains. Clinical trial data on synthetic psilocybin do not generalize to public use due to strict participant selection and controlled environments. Co-use with cannabis is common and may increase the risk of adverse events. The expanding use of unregulated psilocybin mushrooms, combined with high variability in composition and common co-use with other substances, raises urgent public health concerns.
JAMA Psychiatry
March 18, 2026
9 citations
A phase 2b randomized clinical trial tested 25 mg of psilocybin with psychotherapy against a 5 mg dose and a placebo (nicotinamide) in 144 adults aged 25 to 65 with treatment-resistant depression who had stopped antidepressants. The primary outcome—a 50% or greater reduction in depression scores at six weeks—was not statistically significant: 17.0% of those receiving 25 mg responded, versus 12.5% on 5 mg and 10.6% on placebo. Exploratory analyses suggested a clinically meaningful reduction in depressive symptoms with the 25 mg dose. The treatment was generally well tolerated, but safety signals included higher reports of suicidal ideation on dosing days and two serious adverse reactions, one case of hallucinogen persisting perception disorder.
JAMA Psychiatry
December 1, 2023
Sanjay J. Mathew, Manish K. Jha, Amit Anand
8 citations
Electroconvulsive therapy (ECT) and ketamine are both used to treat treatment-resistant depression (TRD), but recent reports highlight important considerations when comparing them. This viewpoint examines key issues from several recent studies, including differences in how quickly each treatment works, their side effects, and the practical challenges of administering them. ECT remains highly effective but requires anesthesia and can cause memory problems, while ketamine offers rapid relief but its long-term effects and optimal dosing are still being studied. The authors suggest that neither treatment is clearly superior for all patients, and the choice depends on individual circumstances and preferences.
JAMA Psychiatry
December 10, 2024
Ethan G. Dutcher, Andrew D. Krystal
5 citations
People with major depressive disorder who had higher expectations for psilocybin treatment showed greater reductions in depression symptoms compared to those taking escitalopram, while expectations for escitalopram did not predict outcomes. The analysis used data from a randomized clinical trial and suggests that treatment expectancies may influence the relative effectiveness of psilocybin versus a standard antidepressant.
JAMA Psychiatry
November 4, 2020
Charles F. Reynolds
5 citations
No Summary