Pharmacological characterisation of psilocybin and 5-MeO-DMT discriminative cues in the rat and their translational value for identifying novel psychedelics
Journal of Psychopharmacology August 27, 2025 Guy A. Higgins, Cam Macmillan, Inés de Lannoy et al. 1 citation
Drug discrimination procedures in rats confirm that hallucinogenic effects of psychedelics like psilocybin, LSD, DMT, and 5-MeO-DMT are mediated primarily by 5-HT2A and 5-HT1A receptors. Plasma levels of psilocin required for generalization in rats (5–52 ng/mL) overlapped with human perceptual effects, while DMT and LSD needed higher exposures in rats than in humans. The duration of drug-lever generalization followed LSD > psilocybin > 5-MeO-DMT ≥ DMT, matching clinical experience. LSD showed a disconnect between plasma exposure and generalization, similar to clinical findings. These results support the translational value of drug discrimination assays for studying psychedelics.