Assessing the Potential Cardiovascular Risk of Microdosing the Psychedelic LSD in Mice
Devin P. Effinger, Serena S. Schalk, Jillian L. King, Janae R. Wallingford, Casey L. O’connell, Joselynn R. Calderon, Benjamin J. Kopecky, John D. Mccorvy, Scott M. Thompson
ACS Pharmacology & Translational Science August 22, 2025 DOI: 10.1021/acsptsci.5c00202 via OpenAlex
Summary
AI-generated from the abstractMicrodosing involves taking psychedelics at doses too low to cause hallucinations, and is popular for supposed cognitive and emotional benefits. Psychedelics bind strongly to 5-HT 2B receptors, which can cause heart disease when chronically activated. In mice, researchers gave either serotonin or d-fenfluramine as positive controls, or low doses of LSD. Serotonin caused significant ventricular thickening at 4 and 8 weeks; d-fenfluramine caused aortic valve regurgitation at 4 weeks. No significant heart changes appeared in any LSD group. LSD, psilocybin, and norfenfluramine had similar affinity and potency at mouse and human 5-HT 2B receptors. Low-dose LSD produced substantial but short-lived receptor activation compared to d-fenfluramine. These data provide no evidence that prolonged low-dose LSD causes heart remodeling in mice.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice |
| Keywords | Pharmacology Medicine |
| Citations | 3 |
| Key finding | Prolonged administration of low-dose LSD in mice produced no evidence of ventricular or valvular heart remodeling. |
Abstract
High Resolution Image Download MS PowerPoint Slide 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-HT 2B 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-HT 2B Rs and observed no significant differences. We calculated that levels of 5-HT 2B 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.