Age- and estrous-dependent effects of psilocybin in rats.

Psilocybin, the psychedelic compound in magic mushrooms, may treat psychiatric disorders, but little is known about how sex and age influence its effects. In a preclinical study on rats, a 1 mg/kg dose of psilocybin did not cause head twitch responses in adolescents but did in adults. Adolescent exposure did not lead to lasting changes in anxiety or behavioral flexibility. Adult females in diestrus had stronger head twitch responses than those in proestrus. The findings indicate age- and sex-dependent differences in psilocybin's effects, with no long-term effects on certain behaviors after adolescent exposure, highlighting the need for inclusive research on age, sex, and hormonal status.

Study at a glance

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.