Age- and estrous-dependent effects of psilocybin in rats.
A L Zylko, R J Rakoczy, B F Roberts, M Wilson, A Powell, A Page, M Heitkamp, D Feist, J A Jones, M S Mcmurray
Neuropharmacology November 15, 2025 Peer reviewed DOI: 10.1016/j.neuropharm.2025.110619 via PubMed
Summary
Psilocybin, a psychedelic from 'magic' mushrooms, did not induce head twitch responses in adolescent rats but did in adults. Additionally, female rats showed increased head twitch responses based on their estrous phase. Importantly, exposure to psilocybin during adolescence did not result in long-term effects on anxiety-related behaviors or behavioral flexibility. These findings indicate that age and sex influence the effects of psychedelics, highlighting the need for inclusive research in this area.
Study at a glance
| Design | preclinical study |
|---|---|
| Population | adolescent and adult rats |
| Key finding | Adolescent rats did not exhibit head twitch responses to psilocybin, while adult rats did, and there were no long-term behavioral effects from adolescent psilocybin 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.