LSD's rapid antidepressant effects are modulated by 5-HT2B receptors.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 16, 2025 Amel Bouloufa, Sarah Delcourte, Renaud Rovera et al. 12 citations
Acute administration of LSD produces fast antidepressant- and anxiolytic-like effects in rats, along with hallucinatory-like effects and suppression of serotonin neuron activity. These effects are blocked by a selective 5-HT2B receptor antagonist, indicating they depend on activation of 5-HT2B receptors. Depletion of serotonin also prevents LSD's effects in the forced swim test and head-twitch response. In mice, LSD fails to produce antidepressant- or anxiolytic-like effects, and its hallucinogenic-like effect is not altered by 5-HT2B receptor blockade. The findings suggest LSD acts as a rapid-onset antidepressant in rats but not in mice, through mechanisms involving 5-HT2B receptor activation.