Age- and estrous-dependent effects of psilocybin in rats.
Alexia L Zylko, Ryan J. Rakoczy, Brianna F Roberts, M Wilson, A Powell, A Page, M Heitkamp, D Feist, J A Jones, Matthew S. Mcmurray
Neuropharmacology November 15, 2025 DOI: 10.1016/j.neuropharm.2025.110619 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Adolescent and adult rats |
| Intervention | Psilocybin |
| Dose | 1 mg/kg intragastric |
| Topics | Psilocybin |
| Citations | 4 |
| Key points | Psilocybin-induced head twitch responses are age- and sex-dependent, with no long-term effects on anxiety or behavioral flexibility after adolescent exposure. |
Abstract
Psilocybin, a psychedelic compound in "magic" mushrooms, has promise as a novel treatment for psychiatric disorders, many of which are more prevalent in females and have onsets during adolescence. However, there is a lack of research about how factors such as sex and age affect responses to psilocybin, as well as potential safety concerns with developmental exposure. The primary objectives of this preclinical study were to determine if psilocybin-induced head twitch responses differ between adolescent and adult rats, and if estrous phase contributes to variation in female head twitch responses. Secondarily, this study sought to determine if treatment with psilocybin during adolescence has long-term effects on anxiety-associated behaviors and behavioral flexibility. Results showed that 1 mg/kg intragastric psilocybin failed to elicit head twitch responses in adolescents (P35 and P45) but elicited robust responses in adult rats. Further, adolescent psilocybin exposure did not cause long-term differences in performance on the elevated zero maze or probabilistic reversal learning tasks. Lastly, adult females in diestrus showed increased head twitch responses after 1 mg/kg psilocybin compared to females in proestrus. Collectively, these results highlight the existence of age- and sex-dependent differences in the effects of psychedelics, while finding no long-term effects on selected behaviors after adolescent exposure. These findings have implications on psychedelic study design, emphasizing the need for inclusive research considering age, sex, and hormonal status.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 6
- Hormonal Influences on Psilocybin Responsivity Across the Female Lifespan: Toward Personalized Psychedelic-Assisted Therapy Psychoactives November 2, 2025
- Dual Modulation of 5-HT2A Receptors and SERT by α-Ethyltryptamine and Its Optical Isomers. ACS Chemical Neuroscience December 17, 2025
- Sex-dependent effects of psychedelics: review of evidence from rodent models Frontiers in Psychiatry July 15, 2026
- Pretreatment with the psychedelic DOI mitigates LPS-induced hippocampal inflammation and behavioral impairments in mice BMC Neuroscience March 24, 2026
- Psilocybin and Chronic Pain: A New Perspective for Future Pain Therapists? Medical Sciences November 20, 2025
and 1 more in the library
Cites 33
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Single-Dose Psilocybin Treatment for Major Depressive Disorder JAMA August 31, 2023
and 28 more in the library