A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder
Raul Escamilla, María Eva González-Trujano, Jesús M. González Mariscal, Jesús Martín Torres-Valencia, Héctor Guzmán-González, José Luis Vega, Anja Loizaga-Velder
Journal of Psychoactive Drugs August 18, 2023 DOI: 10.1080/02791072.2023.2246459 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Research project design with preclinical and clinical experimental components Peer reviewed |
|---|---|
| Population | Healthy adults and patients with major depressive disorder |
| Topics | Psilocybin Psychedelic-assisted therapy Depression |
| Keywords | Major depression Psilocybe mushrooms Psychedelic medicine Mental health treatments Psilocybin therapy Depression research |
| Citations | 7 |
| Key findings | Psilocybin is a novel and breakthrough therapy for major depression, but research in Mexican populations is lacking, and this proposal outlines a preclinical and clinical study design. |
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.
Comparable studies
Other preclinical and animal studies on psilocybin and psychedelic-assisted therapy, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories. Male and female Marchigian Sardinian alcohol-preferring (msP) rats | 2023 | Preclinical experimental study | |
| Synergistic behavioral and neuroplastic effects of psilocybin-NMDAR modulator administration ICR male mice | 2025 | Observational study | |
| Efficient Acyloxymethylation of Psilocin and Other Tryptamines Yielding ACOM Prodrugs for Psychedelic-Assisted Therapy. | 2025 | In vitro study |
Citations in the library
Cited by 7
- “The mushroom was more alive and vibrant”: Patient reports of synthetic versus organic forms of psilocybin Journal of Psychedelic Studies October 29, 2024
- Psilocybin Mushrooms and Public Health in Brazil: Insights from a Retrospective Analysis of Adverse Events and Their Implications for Regulatory Discussions. International journal of medicinal mushrooms 2025
- Psilocybin mushrooms and public health in Brazil: a low-risk adverse event profile calls for evidence-based regulatory discussions medRxiv July 12, 2024
- Naturally Derived Psilocybin for Therapeutic Use: A Six-Criterion Framework for Evidence, Safety, and Benefit–Risk Considerations in Policy and Clinical Development Biomolecules July 3, 2026
- Usos recreativos, medicinales y etnobotánicos de hongos alucinógenos: una revisión Multidisciplinary Collaborative Journal July 1, 2026
and 2 more in the library
Cites 44
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
and 39 more in the library