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.
Translational Psychiatry
September 15, 2015
Matthew B Young, Raül Andero, Kerry J. Ressler et al.
137 citations
MDMA (ecstasy) enhances the extinction of fear memories in mice through a mechanism dependent on brain-derived neurotrophic factor (BDNF). When administered before extinction training, MDMA persistently improved long-term extinction of conditioned fear. The drug increased Fos expression in the amygdala and medial prefrontal cortex, while BDNF expression rose specifically in the amygdala after extinction training. Direct infusion of MDMA into the basolateral amygdala recapitulated the extinction enhancement, and blocking BDNF signaling abolished it. These findings suggest MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders involving altered fear learning.
Psychopharmacology
July 24, 2017
Matthew B Young, Seth D. Norrholm, Lara M. Khoury et al.
103 citations
MDMA enhances the extinction of fear memories in a translational behavioral model, an effect that depends on the serotonin transporter (5-HTT) and the 5-HT2A receptor. These findings support the potential use of MDMA as an adjunct to exposure therapy for fear-related disorders and highlight important pharmacological considerations for patients who are often treated with serotonin reuptake inhibitors.
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 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.
European Psychiatry
March 1, 2023
Guy M. Goodwin, Lindsey Marwood, S. Mistry et al.
1 citation
A single dose of COMP360 psilocybin 25mg, a synthetic form of psilocybin, rapidly improved symptoms of depressed mood and anhedonia in adults with treatment-resistant depression, compared with a 1mg dose. Improvements were apparent by the day after administration and lasted up to 12 weeks for some symptoms. At Week 3, the largest differences on the clinician-rated MADRS scale were for Inability to Feel, Apparent Sadness, Lassitude, and Reported Sadness; on the self-rated QIDS-SR16, the largest difference was for Feeling Sad. The 10mg dose showed intermediate effects, suggesting a dose-related response.
J Affect Disord
October 10, 2025
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
correction
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