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 of Assessing the Potential Cardiovascular Risk of Microdosing the Psychedelic LSD in Mice
“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.”
Authors: Devin P. Effinger, Serena S. Schalk, Jillian L. King, Janae R. Wallingford, Caden K. O’Connell, Joselynn R. Calderon, Benjamin J. Kopecky, John D. McCorvy & Scott M. Thompson
Summary of Assessing the Potential Cardiovascular Risk of Microdosing the Psychedelic LSD in Mice
Effinger and colleagues begin by situating their study within the rising interest in psychedelic use, particularly microdosing practices. Microdosing refers to the repeated consumption of very small, subhallucinogenic doses of psychedelics such as LSD or psilocybin, often claimed to improve mood, cognition, and creativity. Between 2015 and 2023, internet searches for microdosing increased more than thirteenfold, especially in US states where psychedelics have been decriminalised, such as Oregon and Colorado. Despite this surge in popularity, the long-term safety of microdosing remains poorly understood.
The authors emphasise a key concern: the role of the serotonin 5-HT2B receptor. Psychedelics strongly activate several serotonin receptors, including 5-HT2A (responsible for hallucinogenic effects) and 5-HT2B (implicated in cardiac health). Previous research on appetite-suppressing drugs like d-fenfluramine showed that chronic activation of 5-HT2B receptors can cause serious heart problems, including valvular disease (where the heart valves do not close properly) and pulmonary hypertension. These findings raise questions about whether long-term microdosing of psychedelics could lead to similar risks.
Although a single high dose of a psychedelic is unlikely to cause cardiovascular damage due to the short duration of receptor activation, chronic low-dose exposure—typical of microdosing—may present a different risk profile. The study therefore set out to investigate whether prolonged administration of microdosed LSD in mice produces measurable signs of cardiac pathology, using both echocardiography (heart imaging) and receptor-binding assays.
Results
Effects of LSD and Serotonin on Behaviour, Heart Rate, and Body Weight
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Assessing the Potential Cardiovascular Risk of Microdosing the Psychedelic LSD in Mice
https://pubs.acs.org/action/showCitFormats?doi=10.1021/acsptsci.5c00202&ref=pdf
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Cite this paper (APA)
Effinger, D. P., Schalk, S. S., King, J. L., Wallingford, J. R., O’Connell, C. K., Calderon, J. R., ... & Thompson, S. M. (2025). Assessing the potential cardiovascular risk of microdosing the psychedelic LSD in mice. ACS Pharmacology & Translational Science.
Study details
Compounds studied
LSD
Topics studied
Microdosing
Safety
Neuroscience
Study characteristics
Animal Study
Bio/Neuro
Compound Details
The psychedelics given at which dose and how many times
LSD 0.01 - 0.03mg | 40x