A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder

Psilocybin, a natural alkaloid in Psilocybe mushrooms endemic to Mexico, represents a novel and breakthrough therapy for major depression. Current antidepressant treatments require prolonged use with modest effects, adverse effects, and relapse upon discontinuation. This report presents a research project design that includes preclinical toxicity and pharmacological evaluation of a Psilocybe cubensis extract in mice, chemical analysis of the mushroom's constituents, and a clinical study. The clinical component will assess safety and tolerated doses in healthy adults via pharmacokinetic measurements, followed by an open trial in patients with major depressive disorder comparing two single doses of Psilocybe cubensis with assisted psychotherapy to traditional care at a Mexican institute.

Study at a glance

Abstract

The pharmacological treatment of depression consists of taking antidepressant drugs for prolonged periods; its modest therapeutic effect can often be associated with significant adverse effects, while its discontinuation can lead to relapses. Psilocybin is today a novel and breakthrough therapy for major depression. It is a natural alkaloid in Psilocybe mushrooms, which are endemic to Mexico. Research on a larger scale is lacking in various populations, including the Mexican people. This proposal contemplates the experimental design of a preclinical (toxicity and pharmacological evaluation of an extract in mice) and clinical study by including the chemical analysis of a species of Psilocybe cubensis mushroom to characterize its main constituents. The clinical study will consider the safety evaluation by exploring tolerated doses of Psilocybe cubensis by measuring pharmacokinetic parameters after oral administration in healthy adults and an open trial on a sample of patients with major depressive disorder to assess the safety and efficacy of fully characterized Psilocybe cubensis in a two-single doses treatment, (with assisted psychotherapy), compared with the traditional care model at the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz in Mexico City. This report presents the design of a research project with preclinical and clinical experimental components.