Depressive Symptoms Significantly Reduced With Psilocybin Single Moderate Dose

Two weeks after a single moderate dose of psilocybin was administered to patients with major depressive disorder, their depressive symptoms significantly improved.

A single, moderate dose of psilocybin in patients with major depressive disorder (MDD) and no unstable somatic conditions significantly reduces depressive symptoms for at least 2 weeks, according to study findings published in eClinicalMedicine.

Researchers sought to evaluate the effect of a single moderate dose of psilocybin vs placebo in patients with MDD. They hypothesized the single, moderate dose of psilocybin to be more efficacious than placebo. The primary outcomes were changes in depression severity from baseline to 14 days after intervention.

This double-blind, placebo-controlled, randomly assigned clinical single-center trial ( Identifier: NCT03715127) included 52 participants diagnosed with MDD and no unstable somatic conditions at the psychiatric university hospital in Zürich, Switzerland between April 2019 and October 2021. Depression severity was assessed with scores from the Montgomery-Åsberg Depression Rating Scale (MADRS) (psilocybin, 24.3; placebo, 24.1) and Beck’s Depression Inventory (BDI) (psilocybin, 26.9; placebo, 25.8).

Participants were randomly assigned 1:1 to receive either a single, moderate dose (0.215 mg/kg body weight) of psilocybin (n=26; 61.5% women; 100% White) or placebo (n=26; 65.4% women; 88.4% White). Patients already taking psychiatric medication were required to discontinue that medication for at least 2 weeks or 5 half-lives of their current antidepressant before beginning this trial treatment.

The results of the present study suggest that a single, moderate dose of psilocybin may be as efficacious in reducing depressive symptoms as the repeated higher doses administered in previous studies while at the same time inducing less adverse events.

Credible absence of suicidal ideation was confirmed before inclusion. Additional requirements included understanding the German language on level C2, being aged 20 to 60 years, and no use of alcohol or psychotropic substances during the study period. Exclusion criteria included alcohol or drug dependence within 3 months of trial, psychosis spectrum disorders and/or mania symptoms in participants or first-degree relatives, anxiety disorders with panic attacks, and anxiety disorders without panic attacks that required pharmacologic treatment. Other than the resident pharmacist, study personnel and participants were blinded to treatment allocation.

Researchers found an absolute decrease in symptom severity 14 days after the intervention in the psilocybin group compared with baseline, significantly larger than decreases in the placebo group; -13.0 points in the MADRS score (95% CI, -15.0 to -1.3; Cohen’s d=0.97; P =.0011), and -13.2 points in the BDI score (95% CI, -13.4 to -1.3; Cohen’s d=0.67; P =.019).

They noted 54% of participants in the psilocybin group met MADRS remission criteria and 46% met BDI remission criteria. There were no reports of serious adverse events. At the 14-day follow-up, they found 58% (MADRS) and 54% (BDI) of the psilocybin group met criteria for treatment response vs 16% (MADRS) and 12% (BDI) of the placebo group. Their hypothesis that a single, moderate dose of psilocybin produces clinically significant antidepressant effects in patients with MDD compared with placebo and controlling for adjunctive psychological therapy is supported.

Researchers found most of the psilocybin group experienced substantial treatment-induced subjective effects measured by the Altered States of Consciousness (ASC) questionnaire, and most of the placebo group reported only minor subjective effects, however 4 participants in the placebo group responded to treatment, 2 of whom showed marked subjective effects on the ASC scale.

Study limitations include a preponderance of White participants limiting generalizability, the single-center design, and lack of empiric control for nonpharmacologic aspects of treatment.

Researchers concluded, “The results of the present study suggest that a single, moderate dose of psilocybin may be as efficacious in reducing depressive symptoms as the repeated higher doses administered in previous studies while at the same time inducing less adverse events.” They wrote, “Existing data on safety and efficacy uniformly suggest that psilocybin-assisted therapy could emerge as an additional option for existing treatments of depression.” They believe larger, multi-center trials are warranted with longer-term follow-ups. This intervention was well-tolerated by all participants.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Psychiatry Advisor


von Rotz R, Schindowski EM, Jungwirth J, et al. Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomized clinical trial. eClinicalMedicine. Published online December 28, 2022. doi:10.1016/j.eclinm.2022.101809