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.
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.
Therapeutic Advances in Psychopharmacology
January 1, 2022
Caroline Hayes, Mourad Wahba, Stuart Watson
17 citations
Psilocybin-assisted psychotherapy faces unique challenges as it moves from research into clinical practice. Patients often arrive with overly positive expectations shaped by media coverage, and the drug's effects can increase suggestibility, requiring specially trained therapists. The authors recommend measures for phase 3 trials and clinicians to address these issues, aiming to help psilocybin become a licensed medication that suitable patients can access relatively easily. Practicing psychiatrists should be aware of these potential pitfalls, as they will be responsible for future prescribing.
BJPsych Open
November 1, 2024
Mourad Wahba, Caroline Hayes, Maartje Kletter et al.
6 citations
A participant in a phase 2b clinical trial of psilocybin for treatment-resistant depression experienced increased suicidal ideation and a prolonged period of severely restricted eating after administration, leading to destabilization and need for support. Despite limited improvement on depression rating scales, the participant found the experience helpful and made beneficial life changes. The case suggests psilocybin can temporarily worsen suicidal ideation and cause prolonged adverse events beyond acute effects, while paradoxically improving functional outcomes not captured by standard scales. Qualitative exploration of serious adverse events and participant accounts is needed to better understand psilocybin's varied outcomes.
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.