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
February 15, 2023
Priel Meir, Leslie Taylor, Jair C Soares et al.
25 citations
Most psychologists are willing to inform eligible patients about psilocybin-assisted therapy if it becomes FDA-approved, but over 90% would still recommend non-psilocybin psychotherapies first. Among 119 surveyed psychologists, 77.4% agreed they would inform patients about PAT, yet 91.6% would prioritize other therapies. Three-quarters endorsed that more knowledge about psilocybin would increase their likelihood of informing patients. Greater openness to engaging patients with PAT was associated with more positive attitudes and beliefs about psilocybin, greater self-reported knowledge, personal psychedelic use, and positive attitudes toward medical cannabis. Attitudes toward medical cannabis and beliefs about psilocybin were the only significant predictors of openness in regression analysis.
The Journal of clinical psychiatry
April 24, 2024
Gregory H Jones, Courtney M Vecera, Ana C Ruiz et al.
13 citations
A single dose of intranasal ketamine (50 mg) produced rapid antidepressant effects compared to placebo in unmedicated inpatients with major depression and current suicidal ideation, but did not significantly reduce suicidal thoughts. Patients with comorbid alcohol use disorder showed a statistical trend toward greater improvement in suicidality, though the primary outcome was not met. The treatment was well tolerated. The antidepressant benefit was largely unaffected by the presence of alcohol use disorder or the type of mood disorder (unipolar or bipolar). Among those receiving ketamine, improvement in depression correlated with reduced suicidal ideation only in patients without alcohol use disorder.
Journal of affective disorders
March 15, 2025
Thomas D Meyer, Maya Ibrahim, Lauren N Vale et al.
6 citations
People with bipolar disorder have been excluded from most psychedelic research due to concerns about triggering mania or psychosis. This study used the Timeline Followback method to assess mood symptoms, substance use, and mental health in individuals with bipolar disorder one month before and three months after their most recent recreational psychedelic experience. Depressive symptoms and cannabis use significantly decreased, and the number of days without mental health symptoms increased. There were no significant changes in manic, psychotic, or anxiety symptoms. The findings suggest psychedelics may be safe and potentially beneficial for bipolar disorder, but randomized controlled trials are needed.
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.
Journal of affective disorders
February 1, 2026
Lauren N Vale, Maya Ibrahim, Leonardo Fávaro-pereira et al.
1 citation
People with bipolar disorder who have used classic psychedelics like psilocybin or LSD hold more positive attitudes toward these substances and score higher on openness to experience compared to those who are only considering use. The two groups do not differ in sociodemographic background or mental health status. Those who have used psychedelics endorse certain motives for use more strongly, while those contemplating use express greater concerns about potential negative effects. The findings suggest that prior psychedelic experience shapes perceptions and motivations, and highlight topics for discussion with individuals with bipolar disorder who may consider psychedelic use, including in clinical trials.
BMJ open
July 13, 2026
Thomas D Meyer, Lauren N Vale, Maya Ibrahim et al.
A protocol describes an upcoming feasibility study testing psilocybin-assisted therapy in 10 outpatients with bipolar II disorder who have mild to moderate passive suicidal thoughts. Participants may receive two oral doses of 25 mg psilocybin about four weeks apart, combined with a structured mindfulness-based cognitive-behavioral therapy protocol. The study aims to assess the acceptability and safety of this approach, measuring changes in suicidality and depressive symptoms, and to gather preliminary data for a future randomized trial. Individuals with bipolar disorder and suicidality have typically been excluded from psilocybin trials due to safety concerns.
Journal of affective disorders
December 15, 2024
Rodrigo Machado-Vieira, Gregory H Jones, Alan C Courtes et al.
Fatigue, a multidimensional condition that often overlaps with depression, responds only modestly to standard antidepressants and mood stabilizers but has shown positive response to intravenous ketamine, which is limited by cost and access. This study evaluated a single 50 mg dose of intranasal ketamine in 28 individuals with major depressive disorder or bipolar depression, about 60% of whom also had alcohol use disorder. The group by time interaction for the NIH-Brief Fatigue Inventory score was significant, favoring intranasal ketamine over placebo at 4, 24, and 48 hours post-treatment. Intranasal ketamine was well-tolerated with minimal adverse effects. The findings suggest intranasal ketamine induces rapid anti-fatigue effects and may serve as an alternative rapid-acting option for fatigue across different medical conditions.