Characterizing psilocybin as an antidepressant for adolescence in male and female rats
OpenAlex – December 22, 2024
Source: OpenAlex
Summary
Psilocybin, a potent hallucinogen, showed rapid antidepressant-like effects in adolescent Sprague-Dawley rats within 30 minutes, a crucial finding for mental health research. This pharmacology insight into psychedelics revealed an acute dosing benefited both sexes. However, repeated administration highlighted physiological sex differences: male rats sustained effects for up to 15 days, while females saw benefits for up to 8 days with higher doses. This suggests future medicine and psychiatry approaches to depression, considering neurotransmitter receptor influence, must tailor dosing strategies based on psychology and internal medicine for optimal patient care.
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.