Behavioral effects of psychedelic and non-psychedelic serotonin 2A receptor agonist drugs in pigs
Neuroscience Applied January 1, 2026 CA Madsen, M. Navarro, E. Kolesnik et al.
By measuring brain serotonin 2A receptor occupancy with PET scans and relating it to plasma drug levels, the authors established dose-occupancy relationships for DMT, psilocybin, LSD, and lisuride in pigs. At doses producing 60–70% occupancy, all drugs elicited headshakes, a behavioral proxy for psychedelic effects. Lisuride produced the most headshakes (16.5 ± 9.4 in 30 min), while psilocybin, DMT, and LSD produced fewer (5.7–6.9). The time course of headshakes matched each drug's plasma pharmacokinetics. The authors argue that comparing 5-HT2AR agonists at similar receptor occupancy is a valid approach for assessing their biochemical and behavioral effects.