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bioRxiv · 10.1101/2025.04.08.647757

Assessing the potential cardiovascular risk of microdosing the psychedelic LSD in mice

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

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.

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Effinger, D., Schalk, S. S., King, J. L., Strong, J. R., O'Connell, C. K., Calderon, J. R., McCorvy, J., Thompson, S. M.. 2025-04-14. Assessing the potential cardiovascular risk of microdosing the psychedelic LSD in mice. https://doi.org/10.1101/2025.04.08.647757

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