Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
September 1, 2023
Guy M Goodwin, Megan Croal, David Feifel et al.
166 citations
A single 25 mg dose of synthetic psilocybin (COMP360) given alongside psychological support to adults with treatment-resistant depression who continued taking a selective serotonin reuptake inhibitor led to a mean reduction of 14.9 points on the Montgomery-Åsberg Depression Rating Scale at three weeks. Twelve of nineteen participants (63.2%) experienced mild treatment-emergent adverse events that resolved the same day, with no serious events or increased suicidal ideation. Response and remission occurred in 8 participants (42.1%). The authors suggest larger controlled trials are needed to determine whether this approach can benefit patients who cannot safely withdraw from antidepressants.
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
August 29, 2025
Niall M. Mcgowan, James Rucker, Rachel Yehuda et al.
10 citations
A single 25 mg dose of psilocybin, given with psychological support, was safe and well-tolerated in 22 adults with PTSD. No serious adverse events occurred, and most side effects (headache, nausea, crying, fatigue) resolved within a day. PTSD symptoms, measured by the CAPS-5 scale, showed a clinically meaningful average decrease of nearly 30 points at 4 and 12 weeks after the dose, and this improvement was linked to the intensity of the psychedelic experience. Functional impairment and quality of life also improved. The open-label design and small sample size mean further controlled trials are needed to confirm efficacy.
Journal of psychiatric research
December 1, 2024
Lindsey Marwood, Megan Croal, Sunil Mistry et al.
9 citations
In a phase II randomized controlled trial of 233 participants with treatment-resistant depression, those who discontinued antidepressant drugs before receiving psilocybin showed no worsening of depression severity during the discontinuation period, comparable baseline suicidality, and no compromise in psilocybin's treatment efficacy or subjective psychedelic effects relative to those who entered the trial antidepressant-free. The findings suggest that antidepressant discontinuation does not limit the feasibility of psilocybin treatment for treatment-resistant depression and support the homogeneity of psilocybin's effects as a monotherapy.
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.