Effinger, D.; Schalk, S. S.; King, J. L.; Strong, J. R.; O'Connell, C. K.; Calderon, J. R.; McCorvy, J.; Thompson, S. M.

Microdosing, the prolonged ingestion of psychedelics at sub-hallucinogenic doses, has gained popularity for its perceived cognitive and emotional benefits. Psychedelics have high affinity for 5-HT2B receptors, which cause heart disease with strong chronic activation. We investigated the effects of microdosed psychedelics on cardiovascular health in mice using electrocardiography after chronically administering either serotonin as a positive control or lysergic acid diethylamide (LSD) at two sub-hallucinogenic doses. Serotonin produced significant ventricular thickening at 4- and 8-weeks. No significant changes were observed in vehicle or LSD groups. We determined the affinity and potency of LSD, psilocybin, and norfenfluramine at mouse and human 5-HT2BRs and observed no significant differences. We calculated that levels of 5-HT2B activation by low-dose LSD were substantial, but short-lived, compared to the cardiotoxin d-fenfluramine. Together, these data provide no evidence of cardiovascular risk associated with prolonged administration of low-dose LSD in mice.