Psilocybin significantly reduces major depressive disorder symptoms: Lancet

A new study by Robin von Rotz and team shows that for at least two weeks, a single modest dose of psilocybin dramatically lowers depressed symptoms. The findings of this study were published in eClinical medicine. 

Psilocybin has been proposed as a unique, fast-acting depression therapy. Two consecutive doses have been proven to considerably lessen symptom severity in an open-label scenario or when compared to a waiting list group. To the best of the researchers' knowledge, no other trial has compared a single moderate dose of psilocybin to a placebo condition; thus, the primary goal of this randomized clinical trial was to investigate the effect of a single moderate dose of psilocybin versus placebo (equal time spent with psychological support in both treatment conditions) in patients with major depressive disorder (MDD).

In this double-blind, randomized clinical experiment, 52 people with major depressive illness and no unstable somatic problems were randomly assigned to receive either a single, moderate dosage (0.215 mg/kg body weight) of psilocybin or placebo, along with psychological support. MADRS and BDI scores were used to quantify depression severity, with primary outcomes defined as changes from baseline to 14 days following the intervention. The experiment was held in the psychiatric university hospital in Zürich, Switzerland, between April 11th, 2019 and October 12th, 2021.

The key findings of this study were

The psilocybin condition had an absolute reduction in symptom severity of 13.0 points compared to baseline, which was significantly greater than 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 just after intervention. 

In the psilocybin condition, 14/26 (54%) subjects satisfied the MADRS remission criteria.

The current findings show that a single, medium dose of psilocybin may be equally effective in lowering depression symptoms as repeated greater doses delivered in prior research, while producing fewer side effects. This conclusion, however, must be verified in future dose-response studies that include long-term follow-up assessments. All individuals tolerated the intervention well. Secondary endpoints indicate widespread improvements in a number of mental disorders. Lastly, greater study into psilocybin's dose-dependent mechanisms of action is required to optimize the psychological treatment paradigm that incorporates psilocybin-assisted therapy.

Reference: 

von Rotz, R., Schindowski, E. M., Jungwirth, J., Schuldt, A., Rieser, N. M., Zahoranszky, K., Seifritz, E., Nowak, A., Nowak, P., Jäncke, L., Preller, K. H., & Vollenweider, F. X. (2023). Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial. In eClinicalMedicine (Vol. 56, p. 101809). Elsevier BV. https://doi.org/10.1016/j.eclinm.2022.101809