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.
In rats that self-administered oxycodone, the psychedelic compound DOI reduced how much they valued the drug, but the effect depended on dose, sex, and how much prior access to oxycodone they had. In rats with short access, DOI lowered demand by decreasing consumption at low prices and making demand more elastic. In rats with long access, low doses of DOI still reduced demand, but high doses increased it. Most of DOI's effects were blocked by a 5-HT2A receptor antagonist, but this antagonist alone also reduced demand in long-access rats. A 5-HT2C receptor antagonist did not block DOI's effects and sometimes added to them.