Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial

This double-blind placebo-controlled study (n=56) found that one psilocybin-assisted therapy (16mg/70kg, 2 prep + 3 integration meetings) session significantly reduced depressive symptoms (MADRS & BDI) in those suffering from a major depressive disorder (MDD, n=26). Fourteen days after the intervention, 54% of those in the psilocybin group met remission criteria (<10 on MADRS).

Abstract

“Background Psilocybin has been suggested as a novel, rapid-acting treatment for depression. Two consecutive doses have been shown to markedly decrease symptom severity in an open-label setting or when compared to a waiting list group. To date, to our knowledge, no other trial compared a single, moderate dose of psilocybin to a placebo condition.

Methods In this double-blind, randomised clinical trial, 52 participants diagnosed with major depressive disorder and no unstable somatic conditions were allocated to receive either a single, moderate dose (0.215 mg/kg body weight) of psilocybin or placebo in conjunction with psychological support. MADRS and BDI scores were assessed to estimate depression severity, while changes from baseline to 14 days after the intervention were defined as primary endpoints. The trial took place between April 11th, 2019 and October 12th, 2021 at the psychiatric university hospital in Zürich, Switzerland and was registered with clinicaltrials.gov (NCT03715127).

Findings The psilocybin condition showed an absolute decrease in symptom severity of −13.0 points compared to baseline and were significantly larger than those in the placebo condition (95% CI −15.0 to −1.3; Cohens’ d = 0.97; P = 0.0011; MADRS) and −13.2 points (95% CI; −13.4 to −1.3; Cohens’ d = 0.67; P = 0.019; BDI) 14 days after the intervention. 14/26 (54%) participants met the MADRS remission criteria in the psilocybin condition.

Interpretation These results suggest that a single, moderate dose of psilocybin significantly reduces depressive symptoms compared to a placebo condition for at least two weeks. No serious adverse events were recorded. Larger, multi-centric trials with longer follow-up periods are needed to inform further optimisation of this novel treatment paradigm.”

Authors: Robin von Rotz, Eva M. Schindowski, Johannes Jungwirth, Anna Schuldt, Nathalie M. Rieser, Katharina Zahoranszky, Erich Seifritz, Albina Nowak, Peter Nowak, Lutz Jäncke, Katrin H. Preller & Franz X. Vollenweider

Summary of Single-dose psilocybin-AT in MDD: RCT

Major depressive disorder (MDD) affects more than 300 million people worldwide, and conventional antidepressants are ineffective. There is a clear need for more effective and rapid-acting antidepressants.

A pilot study and two controlled clinical trials have shown that psilocybin, a preferential serotonin 1A/2A receptor agonist, rapidly and sustainably alleviates depressive symptoms in MDD. However, the primary efficacy endpoint did not reach statistical significance.