The psychedelic (-)-2,5-dimethoxy-4-iodoamphetamine [(-)-DOI] demonstrates efficacy in reducing cocaine reward and motivation in male rats.
Psychopharmacology August 1, 2025 Leah M Salinsky, Christina R Merritt, Erik J Garcia et al. 8 citations
A single dose of the psychedelic compound (-)-DOI, which activates the 5-HT2A serotonin receptor, reduced cocaine intake and motivation for cocaine in male rats. The drug made cocaine less rewarding and made rats more sensitive to price increases, effectively devaluing the drug. Blocking the 5-HT2A receptor with M100907 eliminated these effects, confirming the receptor's role. The findings suggest that 5-HT2A receptor-acting psychedelics may hold promise for reducing cocaine use, warranting further preclinical research into their effects on intake and relapse.