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
Lea J. Mertens, Michael Koslowski, Felix Betzler et al.
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
February 12, 2025
Brian S. Barnett, Roger D. Weiss, Gerard Sanacora
7 citations
Ketamine's use in psychiatry presents safety challenges, including risks of misuse, adverse effects, and lack of standardized protocols. Recommendations to optimize patient safety include careful patient selection, monitoring during and after administration, and establishing guidelines for appropriate use in clinical settings.
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
JAMA Psychiatry
April 15, 2026
Diana Orsini, Sabrina Wong, Sara Di Luch et al.
4 citations
In randomized clinical trials of psychedelic drugs for psychiatric disorders, the drugs' strong subjective effects often reveal which treatment participants or raters think they received, a phenomenon called functional unblinding. A systematic review of 112 trials found that only 29.5% assessed whether blinding was maintained, yet 57.1% cited blinding as a limitation. Blinding failure exceeded 90% in psilocybin, LSD, and ayahuasca studies and 85% in MDMA trials with inert placebos. Ketamine trials rarely assessed blinding but fared better when midazolam was used as an active comparator. No control strategy consistently preserved ideal blinding, raising concerns about the validity of efficacy estimates.
JAMA Psychiatry
August 1, 2021
James C. Harris
4 citations
No Summary
JAMA Psychiatry
March 25, 2026
Wiesław Jerzy Cubała, Malek Bajbouj, Michael Bauer et al.
3 citations
A single day of treatment with an inhaled synthetic formulation of mebufotenin (GH001) significantly reduced depression symptoms in adults with treatment-resistant depression compared to placebo. In a randomized, double-blind trial of 81 patients, those receiving up to three escalating doses of GH001 showed an average 15.5-point greater improvement on the Montgomery-Åsberg Depression Rating Scale by day 8 than those on placebo. Remission rates were 57.5% for GH001 and 0% for placebo. No severe or serious adverse events occurred. The findings suggest GH001 may be a rapid-acting, well-tolerated treatment option for treatment-resistant depression.
JAMA Psychiatry
February 10, 2021
Alan K. Davis, Roland R. Griffiths
3 citations
No Summary
JAMA Psychiatry
April 10, 2024
Eiko I. Fried, Ioana A. Cristea, Florian Naudet
2 citations
A letter to the editor raises three concerns about a published study that tested 25 mg of psilocybin in 15 patients with treatment-resistant type 2 bipolar depression. The authors of the letter identify specific methodological issues with the study protocol but do not present new data or findings.
JAMA Psychiatry
December 6, 2023
David B. Yaden, Natalie Gukasyan, Sandeep M. Nayak
2 citations
No Summary
JAMA Psychiatry
March 18, 2026
James I. Hudson, Harrison G. Pope
1 citation
A guided psychedelic experience with psilocybin may treat refractory depression by inducing a mystical experience, rather than through a simple biological drug effect. The text suggests that the therapeutic benefit could stem from the profound, transformative nature of the experience, as conceptualized by William James.
JAMA Psychiatry
April 10, 2024
Scott T. Aaronson, Andrew van der Vaart, Harold A. Sackeïm
No Summary
JAMA Psychiatry
December 1, 2023
Chittaranjan Andrade
Ketamine, an anesthetic with a history of recreational use, is being investigated for new on- and off-label indications across medical disciplines, including treatment-resistant depression, chronic pain, and other conditions. The article discusses the expanding experimental and clinical applications of ketamine, highlighting its potential benefits and risks as research progresses.
JAMA Psychiatry
July 15, 2026
No Summary
JAMA Psychiatry
July 15, 2026
No Summary
JAMA Psychiatry
July 15, 2026
Brian S. Barnett, Franklin King
The regulation of Schedule I substances like psychedelics can follow a pathway similar to that of sodium oxybate, a product of gamma-hydroxybutyrate (GHB). This Viewpoint reviews the case of sodium oxybate to illustrate how such substances might navigate regulatory approval despite their current legal status.
JAMA Psychiatry
July 15, 2026
This commentary examines the design and interpretation of clinical trials involving psychedelics, highlighting methodological challenges such as blinding, expectancy effects, and the influence of the therapeutic setting on outcomes. It argues that these factors complicate the attribution of therapeutic benefits solely to the drug itself and calls for more rigorous and nuanced approaches in future research.
JAMA Psychiatry
January 1, 2026
Jack D. C. Dahan, Jasper B. Zantvoord, Anja Lok et al.
A rigorous investigation of psychedelic experience requires studying both its neurobiological changes and its subjective dimensions, as these two domains are equally important for understanding the full effects of psychedelics.
JAMA Psychiatry
August 1, 2025
Christopher Poppe, Jan Christoph Bublitz, Dimitris Repantis
The viewpoint argues that psychedelic treatment should be offered to individuals with psychiatric conditions as a form of life-preserving care prior to physician-assisted death, suggesting it may provide relief and reduce suffering, potentially altering the trajectory toward assisted death.
JAMA Psychiatry
November 1, 2024
Ioana Alina Cristea, Pim Cuijpers, Joar Øveraas Halvorsen
The validity of clinical trials of MDMA-assisted psychotherapy for PTSD depends heavily on the quality of the psychotherapy component, which has been underappreciated in evaluations of the evidence. The authors argue that the psychotherapy itself must be carefully examined to properly interpret trial results and that its role is critical yet often overlooked.
JAMA Psychiatry
September 1, 2023
Luana Colloca, Sina Nikayin, Gerard Sanacora
Expectations—what patients believe will happen—can powerfully shape the outcomes of psychedelic drug therapy. The article discusses how these beliefs interact with the pharmacological effects of psychedelics, potentially amplifying or diminishing therapeutic benefits. It suggests that managing expectations through preparation and the therapeutic setting may be as important as the drug itself. The authors argue that understanding this interplay is crucial for designing effective treatments and for interpreting clinical trial results.