Psilocybin and Psilocybe cubensis extract exhibit divergent behavioural and toxicological effects in rats

Background: Psilocybin, a key psychoactive compound found in Psilocybe mushrooms, has gained increasing attention due to its therapeutic potential in neuropsychiatric disorders [1]. However, comparative preclinical data between isolated psilocybin and whole mushroom extracts remain scarce, particularly regarding behavioural reinforcement and peripheral toxicity [2,3]. Objective: To compare the behavioural and toxicological effects of pure psilocybin and Psilocybe cubensis extract in Wistar Han rats. Methods: Male Wistar Han rats (n=18) were randomly assigned to control (0.9% NaCl), pure psilocybin (3 mg.kg⁻¹), or P. cubensis extract (equivalent to 3 mg·kg⁻¹ psilocybin/psilocin) groups. Treatments were administered orally. Behavioural effects were assessed using a conditioned place preference (CPP) paradigm, with evaluations at 1, 7, and 14 days post-treatment. Locomotor/exploratory activity was estimated by compartment entries. Peripheral effects were evaluated through relative organ weights and lipid peroxidation (TBARS assay) in the heart, brain, liver, and kidney. Statistical analysis was performed using ANOVA (p