ACS Pharmacology & Translational Science
August 22, 2025
Devin P. Effinger, Serena S. Schalk, Jillian L. King et al.
3 citations
Microdosing 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.
bioRxiv (Cold Spring Harbor Laboratory)
April 14, 2025
Devin P. Effinger, Serena S. Schalk, Jillian L. King et al.
2 citations
preprint
Chronic administration of low-dose LSD in mice does not produce the cardiovascular damage seen with serotonin, a known cardiotoxin. Serotonin caused significant ventricular thickening after 4 and 8 weeks, while LSD at two sub-hallucinogenic doses showed no such changes. Although LSD activates 5-HT 2B receptors—the same receptors linked to heart disease from chronic activation—the activation is substantial but short-lived compared to the cardiotoxin d-fenfluramine. Affinity and potency of LSD, psilocybin, and norfenfluramine at mouse and human 5-HT 2B receptors were similar. These findings indicate no evidence of cardiovascular risk from prolonged low-dose LSD in mice.
ACS Chemical Neuroscience
May 27, 2026
Grant C. Glatfelter, Serena S. Schalk, Donna Walther et al.
Tryptamine psychedelics produce their effects mainly by activating serotonin 2A receptors, but many also affect other targets. 4-MeO-MiPT, a compound that both activates 5-HT2A receptors and blocks the serotonin transporter (SERT), produces blunted psychedelic effects in humans. In mice, 4-MeO-MiPT and its analogs with stronger SERT blockade showed fewer head twitch responses (a proxy for psychedelic-like effects) than their 4-hydroxy counterparts. Pretreating mice with the SERT inhibitor fluoxetine reduced head twitch responses from 4-hydroxy compounds to levels seen with the 4-methoxy analogs. The findings suggest that dual 5-HT2A/SERT ligands may have therapeutic potential with reduced acute psychedelic effects.