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.
Current psychiatry reports
October 1, 2022
Gregory S Barber, Scott T Aaronson
56 citations
For patients with mood disorders or PTSD who have not responded to multiple treatments, few options exist. After decades of federal restrictions on psychedelic research, recent studies have re-examined compounds like MDMA and psilocybin. These investigations involve safe administration in controlled settings, preceded by hours of participant preparation and followed by integration sessions. The improvements participants experience appear linked to profound shifts in perspective, distinct from those achieved with current standard care. Studies have addressed treatment-resistant depression, end-of-life despair, and PTSD. Psychedelic psychotherapy, combining biological therapy with psychotherapy, may transform mental health care.
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.
American Journal of Psychiatry
January 1, 2025
Scott T Aaronson, Andrew van der Vaart, Tammy Miller et al.
31 citations
In an open-label study, psilocybin appears effective and safe for people with severe treatment-resistant depression, supporting further research into psychedelics for this group, including how post-traumatic stress disorder may affect outcomes.
Journal of affective disorders
April 1, 2023
Nadav Liam Modlin, Tammy M Miller, James J Rucker et al.
30 citations
Psilocybin therapies show promise for conditions like major depressive disorder, end-of-life anxiety, and obsessive-compulsive disorder. However, little attention has been paid to intrapersonal and interpersonal factors that influence a patient's readiness for such interventions. This paper proposes that readiness assessment should include both intrapersonal and interpersonal factors to improve safety, patient care, and treatment outcomes. Although no reliable and valid instrument currently exists, the authors suggest three areas of focus—patient presentation, therapeutic alliance, and patient safety—to establish readiness and optimize and personalize psilocybin therapy.
Brain stimulation
January 1, 2024
Charles R Conway, Scott T Aaronson, Harold A Sackeim et al.
16 citations
Patients with treatment-resistant unipolar major depressive disorder who qualified for the RECOVER trial—the largest randomized sham-controlled study of vagus nerve stimulation for a psychiatric condition—had severe disability, a median of 11.0 prior failed antidepressant treatments, and high rates of suicidality (77% with suicidal ideation, 40% with previous suicide attempts). Seventy-one percent had received at least one prior interventional psychiatric treatment (electroconvulsive therapy, transcranial magnetic stimulation, or esketamine). Compared to those without such history, recipients of interventional treatments were younger, more severely depressed, had greater suicidal ideation, earlier onset of depression, and more failed medication trials.
Expert Opinion on Investigational Drugs
October 3, 2023
Zofia Kozak, Matthew W Johnson, Scott T Aaronson
10 citations
Patients with treatment-resistant depression may be the most suitable candidates for psilocybin treatment when weighing known risks and benefits against existing standards of care. Much remains unknown about the risks of psilocybin treatment.
Journal of psychiatric practice
September 1, 2023
Amir Garakani, Jeanne L Alexander, Calvin R Sumner et al.
6 citations
Public and clinical interest in psychedelics is growing, with many studies underway for depression, anxiety, PTSD, and substance use disorders. This paper focuses on psilocybin, explaining its mechanism, psychedelic effects, and dosing. It reviews treatment studies, primarily for treatment-resistant depression and cancer-related anxiety, and discusses future directions and potential limitations in studying and regulating psilocybin and other psychedelics.
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.
The Journal of clinical psychiatry
May 13, 2026
Andrew van der Vaart, Jeffrey LaPratt, Kimberly Swartz et al.
A single 25-mg dose of a synthetic psilocybin formulation, combined with psychological support, rapidly and durably reduced chronic suicidal ideation and depressive symptoms in 20 adults with major depressive disorder who had not responded to at least two prior antidepressant treatments. Suicidal ideation scores dropped significantly by week 1, remained reduced at week 3 (the primary endpoint), and were still lower at week 12, when 70% of participants had minimal or no suicidal ideation. Depressive symptoms also improved substantially. No serious adverse events occurred. The findings are preliminary and require confirmation in larger randomized trials.