Potential Differences in Psychedelic Actions Based on Biological Sex.
Sheida Shadani, Kyna Conn, Zane B. Andrews, Claire J. Foldi
Endocrinology July 1, 2024 DOI: 10.1210/endocr/bqae083 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Psilocybin Serotonin |
| Keywords | Cognition Learning Sex differences Psychedelics hallucinogens Entheogens Psychoactive drugs Hormones estrogen Progesterone Endocrine Neuroscience brain chemistry Neurotransmitters |
| Citations | 49 |
| Key findings | Estrogen-serotonin interactions may influence the efficacy of psychedelics in female participants, potentially modifying therapeutic effects across menstrual cycles and developmental stages. |
Abstract
The resurgence of interest in psychedelics as treatments for psychiatric disorders necessitates a better understanding of potential sex differences in response to these substances. Sex as a biological variable (SABV) has been historically neglected in medical research, posing limits to our understanding of treatment efficacy. Human studies have provided insights into the efficacy of psychedelics across various diagnoses and aspects of cognition, yet sex-specific effects remain unclear, making it difficult to draw strong conclusions about sex-dependent differences in response to psychedelic treatments. Compounding this further, animal studies used to understand biological mechanisms of psychedelics predominantly use one sex and present mixed neurobiological and behavioral outcomes. Studies that do include both sexes often do not investigate sex differences further, which may hinder the translation of findings to the clinic. In reviewing sex differences in responses to psychedelics, we will highlight the direct interaction between estrogen (the most extensively studied steroid hormone) and the serotonin system (central to the mechanism of action of psychedelics), and the potential that estrogen-serotonin interactions may influence the efficacy of psychedelics in female participants. Estrogen influences serotonin neurotransmission by affecting its synthesis and release, as well as modulating the sensitivity and responsiveness of serotonin receptor subtypes in the brain. This could potentially influence the efficacy of psychedelics in females by modifying their therapeutic efficacy across menstrual cycles and developmental stages. Investigating this interaction in the context of psychedelic research could aid in the advancement of therapeutic outcomes, especially for conditions with sex-specific prevalence.
Comparable studies
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Citations in the library
Cited by 55
- Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Neuroscience & Biobehavioral Reviews September 20, 2024
- Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications Pharmaceuticals January 19, 2025
- Psilocybin as a novel treatment for chronic pain British Journal of Pharmacology November 29, 2024
- Clinical and preclinical evidence of psilocybin as antidepressant. A narrative review Progress in Neuro-Psychopharmacology and Biological Psychiatry 2025
- Females in Psychedelic Research: A Perspective for Advancing Research and Practice. ACS Pharmacology & Translational Science July 11, 2025
and 50 more in the library
Cites 63
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- 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
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