Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder

This randomized open-label study (n=24) found that two sessions with psilocybin (20 and 30mg/70kg) significantly improved depression scores for a population with major depressive disorder (MDD) up to 8 weeks later.

Abstract

Importance Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression.

Objective To investigate the effect of psilocybin therapy in patients with MDD.

Design, Setting, and Participants This randomized, waiting list–controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population).

Interventions Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay.

Main Outcomes and Measures The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR).

Results Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.2; 95% CI, 1.4-3.0; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.7-3.6; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 3.0; 95% CI, 1.9-4.0; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 3.1; 95% CI, 1.9-4.2; P < .001). In the overall sample, 17* participants (71%*) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score).

Conclusions and Relevance Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression.

Authors: Alan K. Davis, Frederick S. Barrett, Darrick G. May, Mary P. Cosimano, Nathan D. Sepeda, Matthew W. Johnson, Patrick H. Finan & Roland R. Griffiths

Notes

This paper is included in our ‘Top 10 Articles on Psychedelics in the Treatment of Depression and Top 10 Articles on Psychedelics in the Year 2020

The significance of this paper is that its the first to use psilocybin for major depressive disorder (MDD), a much broader category than treatment resistant depression (TRD).

“This study was funded in part by a crowd-sourced funding campaign organized by Tim Ferriss; a grant from the Riverstyx Foundation; and grants from Tim Ferriss, Matt Mullenweg, Craig Nerenberg, Blake Mycoskie, and the Steven and Alexandra Cohen Foundation…”

This paper was also reported on in New Atlas, Hopkins Medicine, Futurity, Scimex, NPR, Bezinga, Healthline,

From the Hopkins publication: “In a small study of adults with major depression, Johns Hopkins Medicine researchers report that two doses of the psychedelic substance psilocybin, given with supportive psychotherapy, produced rapid and large reductions in depressive symptoms, with most participants showing improvement and half of study participants achieving remission through the four-week follow-up.

You can find a talk by Alan Davis here, an interview with Roland Griffiths here, and that of a participant here.

In the first video, Roland Griffiths does note that much larger trials are needed and will take up to four years to be completed.

*There was a small correction to this study published that stated that this number should have been 71% (instead of the originally reported 67%, or 17 versus 16 of the participants).

Find this paper

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder

https://doi.org/10.1001/jamapsychiatry.2020.3285

Open Access | Google Scholar | Backup | 🕊

Published in
JAMA Psychiatry
November 4, 2020
397 citations

Study details

Compounds studied
Psilocybin

Topics studied
Depression

Study characteristics
Original Open-Label Randomized

Participants
24 Humans

Authors

Authors associated with this publication with profiles on Blossom

Frederick Barrett
Frederick Streeter Barrett is an Assistant Professor of Psychiatry and Behavioral Sciences and works at the Johns Hopkins University Center for Psychedelic and Consciousness Research.

Matthew Johnson
Matthew Johnson is an Associate Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University. His research is concerned with addiction medicine, drug abuse, and drug dependence.

Roland Griffiths
Roland R. Griffiths is one of the strongest voices in psychedelics research. With over 400 journal articles under his belt and as one of the first researchers in the psychedelics renaissance, he has been a vital part of the research community.

Institutes

Institutes associated with this publication

Johns Hopkins University
Johns Hopkins University (Medicine) is host to the Center for Psychedelic and Consciousness Research, which is one of the leading research institutes into psychedelics. The center is led by Roland Griffiths and Matthew Johnson.

National Institute on Drug Abuse
This company doesn't have a full profile yet, it is linked to a clinical trial.

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 20 - 30
mg | 2x

Linked Research Papers

Notable research papers that build on or are influenced by this paper

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up
This 12-month follow-up study (n=24) assessed the efficacy and safety of psilocybin in depressed participants from a previous trial. A durable antidepressant effect was observed with treatment response (⩾50% reduction in GRID-HAMD score from baseline, Cohen d = 2.4) and rate of remission at 75% and 58%, respectively, at 12 months. No serious adverse events related to psilocybin were observed.

Linked Clinical Trial

Effects of Psilocybin in Major Depressive Disorder
The proposed pilot study will assess whether people with major depressive disorder experience psychological and behavioral benefits and/or harms from psilocybin.