Characterizing psilocybin as an antidepressant for adolescence in male and female rats
Rubén García‐cabrerizo, Itziar Beruete-Fresnillo, M. Julia García‐fuster
bioRxiv (Cold Spring Harbor Laboratory) December 22, 2024 preprint DOI: 10.1101/2024.12.20.629571 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study |
|---|---|
| Population | Adolescent Sprague-Dawley rats |
| Intervention | Psilocybin |
| Duration | Acute (30 minutes post-treatment) and repeated daily over 7 days with follow-up up to 15 days post-treatment |
| Topics | Anxiety Psilocybin |
| Keywords | Antidepressant Dosing Depression economics Imipramine Pharmacology Physiology Hallucinogen |
| Citations | 2 |
| Key findings | A single dose of psilocybin produced rapid antidepressant-like effects in both male and female adolescent rats, but repeated daily dosing revealed sustained effects in males and shorter, dose-dependent effects in females. |
Abstract
Abstract Adolescent depression is a significant public health concern, yet treatment options remain limited, particularly due to age- and sex-related differences in antidepressant efficacy. This study explored the rapid and long-lasting antidepressant-like potential of psilocybin in adolescent Sprague-Dawley rats, examining acute and repeated oral dosing effects while incorporating sex as a biological variable. An acute administration of psilocybin produced rapid antidepressant-like effects 30 minutes post-treatment in both male and female rats, demonstrated by reduced immobility and increased escape-related behaviour in the forced swim test. However, repeated daily administrations over 7 days revealed notable sex differences. In males, the antidepressant-like effects were sustained, at least, for up to 15 days post-treatment at both tested doses. In contrast, in females, the effects were dose-dependent and less enduring, persisting only up to 8 days at the highest dose tested. To the best of our knowledge, these results are the first ones to underscore psilocybin’s potential as a fast-acting and long-lasting antidepressant during adolescence, a developmental stage marked by high vulnerability to depression and reduced response to conventional treatments, while also emphasizing the importance of tailoring therapeutic approaches to individual biological factors such as sex.