The New England journal of medicine
November 3, 2022
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
1,095 citations
A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.
Journal of Affective Disorders
February 3, 2023
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
168 citations
Three weeks after a single dose, 25 mg of psilocybin, and to a lesser extent 10 mg, improved patient-reported measures of depression severity, anxiety, affect, and functioning in people with treatment-resistant depression. These findings extend the primary results from the largest randomized clinical trial of psilocybin for TRD, highlighting outcomes that matter to patients.
Frontiers in Psychiatry
February 9, 2023
Kees Kramers, Arnt Schellekens, Metten Somers et al.
119 citations
A systematic review of psilocybin-assisted therapy for substance use disorders identified four clinical trials (six articles) involving 151 patients, with doses from 6 to 40 mg. Three studies focused on alcohol use disorder and one on tobacco use disorder. In a pilot study (n=10), heavy drinking days decreased significantly. In another single-arm study (n=31), 32% achieved complete alcohol abstinence over an average of 6 years. A double-blind, placebo-controlled RCT (n=95) found significantly fewer heavy drinking days with psilocybin versus placebo. In a pilot study (n=15), smoking abstinence at 26 weeks was 80% and at 52 weeks 67%. All trials indicated beneficial effects, but larger RCTs are needed.
Journal of affective disorders
March 1, 2025
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
35 citations
In treatment-resistant depression, a single dose of 25 mg of psilocybin produced stronger correlations between certain psychedelic experiences and depression improvement three weeks later than lower doses. The intensity of psychedelic effects was dose-related, but scores for different doses overlapped considerably. At the 25 mg dose, dimensions of oceanic boundlessness and visual restructuralization, along with emotional breakthrough, showed the strongest correlations with reduced depression scores. The study does not establish causation and requires replication. The overlap in experience intensity across doses suggests unblinding to dose is less likely. Correlations between psychedelic experience and outcome indicate specificity in psilocybin's mechanism of action.
Journal of Psychopharmacology
December 10, 2024
Mattia Marchi, Riccardo Farina, Karim Rachedi et al.
13 citations
A systematic review and network meta-analysis of nine randomized controlled trials involving 606 participants with terminal illnesses found that psychedelic compounds—psilocybin, ketamine, MDMA, and LSD—significantly reduced depression (standardized mean difference −0.80) and anxiety (standardized mean difference −0.84) compared to control conditions. Psilocybin appeared most effective for depression, and LSD for anxiety, though direct comparisons between psychedelics did not show statistically significant differences. Rates of treatment discontinuation and adverse events were similar between psychedelic and control groups. The findings suggest psychedelics, particularly psilocybin and LSD, may help alleviate existential distress in end-of-life care, but limitations include few trials, blinding challenges, and a lack of head-to-head comparisons.
Neuroscience & Biobehavioral Reviews
December 16, 2025
Rivka Vollebregt, A. J. Storm, Paul J. Lucassen et al.
3 citations
Classical psychedelics such as LSD, DMT, and psilocybin primarily act as serotonin 5-HT2A receptor agonists, initiating intracellular signaling that modulates neuroplasticity, glutamate release, and cortical excitability. They disrupt functional network connectivity, especially within the default mode network, while enhancing global integration across brain regions. These effects are linked to subjective experiences like ego dissolution and altered perception, which may contribute to therapeutic benefits in conditions such as treatment-resistant depression. The review synthesizes molecular and network-level findings from 1990 onward, noting that overlapping theories are beginning to bridge receptor activity with large-scale brain connectivity changes, though no single model explains all effects.
Journal of affective disorders
August 1, 2026
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
2 citations
In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.
American Journal of Psychiatry
March 1, 2025
Metten Somers, Floortje E. Scheepers
1 citation
No Summary
The Journal of Clinical Psychiatry
October 13, 2025
Pim B. van der Meer, Sebastiaan O Verboeket, Arjen J. C. Slooter et al.
NMDA receptor antagonists like ketamine may help treat catatonia. This systematic review evaluated the efficacy and safety of ketamine and esketamine for catatonia, finding that the available evidence suggests these drugs could be beneficial, but the data are limited and further research is needed to confirm their role.
Psychedelic Medicine
October 8, 2025
Pim B. van der Meer, Nout Schukking, Miranda G. Dik et al.
A systematic review of clinical trials found limited evidence that psychoactive tryptamines other than psilocybin and ibogaine are effective for treating substance use disorders. Four trials involving 176 patients with alcohol use disorder tested dipropyltryptamine and diethyltryptamine. Abstinence rates ranged from 10% to 38% at 26 weeks of follow-up, and severity of alcohol use did not differ between the tryptamine and control groups. Adverse effects were poorly reported. The review concludes that studies are scarce and show limited evidence for effectiveness in treating addictive disorders.