Hormonal Influences on Psilocybin Responsivity Across the Female Lifespan: Toward Personalized Psychedelic-Assisted Therapy
Response to psilocybin may vary across a woman’s lifespan, mediated by the impact of Oestrogen - review of current literature suggests more research is needed on the impact of sex hormones
Today’s research highlights the therapeutic potential of the hallucinogen psilocybin in the treatment of pathologies associated with mood, cognitive, and affective dysregulation. These domains of function are regulated by the serotonergic system, which can be influenced by sex hormones, like estrogen and testosterone, and psychedelic compounds including psilocybin.
Current evidence supports a higher prevalence of affective disorders in females, and a growing awareness of sex-based differences in response to drug therapy. Estrogen’s influence on serotonin physiology is an aspect that must be accounted for when planning a treatment regimen that includes a psychoactive drug such as psilocybin.
A review of the current literature was conducted, and an analysis of how the fluid hormonal states in females across their different reproductive phases may impact serotonin dynamics, synaptic plasticity, and therapeutic timing of psilocybin use is discussed. Future research should focus on the influence of sex hormones on psychedelic-assisted therapy in the effort to further personalise treatment plans for these pathologies.
Comments - This review by Ekoh et al. (2025) explores how fluctuations in sex hormones across the female lifespan may modulate responsiveness to psilocybin-assisted therapy. The authors highlight that oestradiol, progesterone, and testosterone influence serotonergic signalling, particularly 5-HT₂A receptor density, serotonin transporter activity, and neuroplasticity pathways such as BDNF and mTOR, which are also key targets of psilocin, the active metabolite of psilocybin. They propose that hormonal states during puberty, menstrual cycling, pregnancy, postpartum, perimenopause, and menopause could affect both the efficacy and subjective experience of psilocybin treatment. Despite growing evidence of sex differences in depression and serotonergic function, most psychedelic trials have not stratified by sex, menstrual phase, hormonal contraceptive use, or menopausal status. The paper calls for sex- and hormone-informed study designs to advance personalised psychedelic therapy, particularly to address mental-health vulnerabilities during hormonally dynamic periods such as perimenopause.
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