Time to embrace the whole: considering the replacement of psilocybin with Psilocybe spp. in psychedelic research and therapy.
Genís Ona, Cristina Llagostera, Oscar Alvarez, Rosa M Dueñas, Débora González, Oscar Soto-Angona
Natural Product Research June 2, 2026 DOI: 10.1080/14786419.2026.2683121 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Perspective or review Peer reviewed |
|---|---|
| Topics | Psilocybin Psychedelic-assisted therapy |
| Keywords | Psychedelics Mushrooms Psilocybe cubensis |
| Key findings | Argues that whole-mushroom extracts from Psilocybe cubensis show enhanced or distinct preclinical effects compared to pure psilocybin and could enable more equitable treatment models. |
Abstract
Psilocybin, the main psychoactive compound in Psilocybe cubensis mushrooms, has gained considerable attention for its therapeutic potential. Current research focuses only on isolated psilocybin, neglecting the broader pharmacological and cultural use of the whole mushroom. This perspective advocates for an integrative approach that includes standardised P. cubensis extracts within the psychedelic research agenda. We review preclinical studies comparing whole-mushroom extracts with pure psilocybin, showing enhanced or distinct effects on synaptic proteins, metabolomic profiles, and behavioural outcomes, including in models of depression and obsessive-compulsive disorder. Furthermore, the use of whole extracts may promote more affordable, equitable, and publicly accessible treatment models, in contrast to high-cost synthetic psilocybin formulations. This article argues for the urgent need to explore whole-mushroom therapeutics, ensuring that decisions in psychedelic medicine are based on a full spectrum of evidence rather than solely on pharmaceutical feasibility.
Comparable studies
Other narrative reviews on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| The pharmacology of psilocybin | 2002 | Review | |
| Serotonin research: contributions to understanding psychoses | 2008 | Review | |
| Psychedelics, Meditation, and Self-Consciousness | 2018 | Review | |
| The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act | 2018 | Review |
Citations in the library
Cites 25
- The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects ACS Pharmacology & Translational Science December 10, 2020
- Serotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response Biomedicine & Pharmacotherapy August 29, 2022
- Toward a Comparative Overview of Dependence Potential and Acute Toxicity of Psychoactive Substances Used Nonmedically The American Journal of Drug and Alcohol Abuse 1993
- Treatment with psychedelics is psychotherapy: beyond reductionism The Lancet Psychiatry December 12, 2023
- Simultaneous Production of Psilocybin and a Cocktail of β‐Carboline Monoamine Oxidase Inhibitors in “Magic” Mushrooms Chemistry - A European Journal November 14, 2019
and 20 more in the library