Differential effects of psilocybin derivatives on fentanyl-induced conditioned place preference in male and female mice
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Updated: Sep 2, 2026
Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
Tiffini N Lovell1, Peter B James2, Skylar L Hodgins2
1Department of Biomedical Sciences, Colorado State University, Fort Collins, USA.
Background:
Fentanyl is the leading cause of fatal overdoses worldwide, and repeated use may lead to substance use disorder (SUD). In SUD, drug-associated contexts can trigger reward-related behavior even in the absence of the drug. Psychedelic compounds may weaken context-drug associations, reducing reward-related behavior to fentanyl.
Aims:
We evaluated the effects of the psychedelic psilocin and its derivatives, 4-MeO-MiPT and 4-HO-MiPT, on fentanyl-induced conditioned place preference (CPP) in male and female C57BL/6J mice.
Methods:
Mice were conditioned to distinct fentanyl and saline control contexts, then assessed for fentanyl place preference before and after treatment with one of the test compounds. Anxiety-related side effects of each compound were evaluated using an elevated plus maze (EPM) model.
Results:
Psilocin reduced fentanyl CPP exclusively in females, 4-MeO-MiPT in both sexes, and 4-HO-MiPT had no effect. None of the compounds significantly altered anxiety-like behaviors in EPM.
Conclusion:
These findings support further preclinical investigations of the sex-dependent effects of psilocin and 4-MeO-MiPT on fentanyl reward behavior.
