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.
Comparable studies
Other preclinical and animal studies on psilocybin for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats Wistar rats | 2018 | Experimental study | n = 40 |
| Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming SAPAP3 knockout mice | 2024 | Randomized controlled trial | n = 50 |
| Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder. Male rats | 2024 | Preclinical study | |
| Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor Mice | 2024 | Experimental study |
Citations in the library
Cited by 3
- Sex-dependent developmental changes in behavior, brain structure, functional connectivity, and sensory perception following exposure to psilocybin during adolescence Neuropsychopharmacology February 18, 2026
- Short- and Long-Acting Psychedelics: Structure-Activity Relationships, Pharmacology, and Implications for Neuropsychiatric Therapeutics. ACS Chemical Neuroscience June 17, 2026
- Beyond head-twitch response: Acute psilocybin affects spontaneous behaviors in rats in a dose-dependent manner. Journal of Psychopharmacology August 25, 2026
Cites 28
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Single-Dose Psilocybin Treatment for Major Depressive Disorder JAMA August 31, 2023
- Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up Journal of Psychopharmacology February 1, 2022
- Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Proceedings of the National Academy of Sciences April 13, 2021
and 23 more in the library