Assessing the Potential Cardiovascular Risk of Microdosing the Psychedelic LSD in Mice
Calderon, J. R., Effinger, D. P., King, J. L., Kopecky, B. J., McCorvy, J. D., O'Connell, C. K., Schalk, S. S., Thompson, S. M., Wallingford, J. R.
This pre-clinical mouse study tested chronic administration of serotonin, d-fenfluramine, or subhallucinogenic doses of LSD on cardiovascular health. Serotonin and d-fenfluramine caused ventricular thickening and valve regurgitation, respectively, while LSD produced no significant ventricular or valvular changes. Receptor binding assays showed LSD, psilocybin, and norfenfluramine had similar affinity for 5-HT2B, but LSD’s activation was short-lived, providing no evidence of heart remodeling with prolonged low-dose LSD.
Abstract
Microdosing, the prolonged ingestion of psychedelics at subhallucinogenic doses, has gained popularity for its perceived cognitive and emotional benefits. Psychedelics have high affinity for 5-HT2B receptors, a receptor known to cause human heart disease with strong chronic activation. We investigated the effects of microdosed psychedelics on cardiovascular health in mice using echocardiography after chronically administering either serotonin or d-fenfluramine as positive controls or lysergic acid diethylamide (LSD) at two subhallucinogenic doses. Serotonin produced significant ventricular thickening at 4- and 8-weeks, and d-fenfluramine caused aortic valve regurgitation at 4-weeks. No significant changes were observed in any vehicle or LSD group. 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 ventricular or valvular remodeling associated with prolonged administration of low-dose LSD in mice.