Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

Document Type

Article

Publication Date

9-5-2023

Publication Title

JAMA : the journal of the American Medical Association

Keywords

california; pni; Adult; Humans; Female; Male; Depressive Disorder, Major; Hallucinogens; Psilocybin; Mental Health; Niacin

Abstract

IMPORTANCE: Psilocybin shows promise as a treatment for major depressive disorder (MDD).

OBJECTIVE: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD.

DESIGN, SETTING, AND PARTICIPANTS: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing.

INTERVENTIONS: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment.

RESULTS: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P

CONCLUSIONS AND RELEVANCE: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03866174.

Clinical Institute

Neurosciences (Brain & Spine)

Clinical Institute

Mental Health

Specialty

Neurosciences

Specialty

Behavioral Health

Specialty

Pharmacy

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