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.
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.
The Journal of clinical psychiatry
March 3, 2025
Guy M Goodwin, Ania Nowakowska, Merve Atli et al.
14 citations
A single 25 mg dose of the synthetic psilocybin formulation COMP360 showed a longer time before depressive events recurred over 52 weeks compared with 1 mg and 10 mg doses in people with treatment-resistant depression. In the full group of 233 participants, the median time to a depressive event was 92 days for the 25 mg group, 83 days for the 10 mg group, and 62 days for the 1 mg group. Most participants had a depressive event by 12 weeks. Adverse events were rare; one case of mild suicidal ideation in the 1 mg group was considered possibly related to the drug. Larger long-term studies are needed to confirm these results.
Journal of affective disorders
May 1, 2023
Guy M Goodwin, Megan Croal, Lindsey Marwood et al.
13 citations
Blinding in psychiatric clinical trials is considered ideal, but unblinding due to subjective drug effects raises concerns about demand characteristics undermining research findings. For conventional antidepressants, the strong link between dose and subjective effects does not correspond to a strong relationship with efficacy in randomized controlled trials, disproving the idea that unblinding primarily drives trial outcomes. Instead, early changes in brain function predict treatment outcomes and align with neuroscience. For psychedelic treatment of depression, unblinding is inevitable, but the therapeutic effect stems directly from serotonin receptor activation and altered brain connectivity, not just expectancy. A dose-response relationship is expected with novel mechanisms. Unblinding does not invalidate genuine recovery.
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.
EClinicalMedicine
December 1, 2025
Nadav Liam Modlin, Victoria Williamson, Guy M Goodwin et al.
2 citations
Psilocybin treatment for post-traumatic stress disorder, when delivered with standardized preparation and support, may allow patients to engage with trauma-related material indirectly through affective, somatic, and self-transcendent experiences, such as feelings of unity or dissolution of self, rather than requiring direct confrontation with traumatic memories as in standard therapies. This qualitative study, nested within a phase 2 trial involving 21 adults with PTSD, identified four core themes: non-pharmacological factors for psychological safety and trust, the experiential nature of psilocybin treatment, engagement with trauma-related material, and comparative reflections on prior therapies. The findings suggest psilocybin offers a meaningful therapeutic opportunity, but larger controlled studies are needed.