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.
bioRxiv (Cold Spring Harbor Laboratory)
April 29, 2022
Devin P. Effinger, Sema G. Quadir, M. C. Ramage et al.
2 citations
preprint
A single dose of psilocin, the active metabolite of psilocybin, produces sex-specific, time-dependent, and lasting changes in central amygdala (CeA) activity and reactivity to an aversive air-puff stimulus in mice. Psilocin acutely increased CeA activity in both sexes and increased stimulus-specific CeA reactivity in females but not males. In males, psilocin caused time-dependent decreases in reactivity from 2 to 28 days after administration, while females showed no such decrease. Behavioral threat responses also changed in a sex-dependent manner, with no effects on exploratory behavior or locomotion. These findings suggest enduring, sex-specific alterations in CeA function underlie psilocin's therapeutic effects in affective disorders.
Translational Psychiatry
June 13, 2026
Jillian L. King, Devin P. Effinger, Cameron Basquez-Pfeifer et al.
The head-twitch response (HTR) in mice, a standard test for hallucinogenic potential, fails to reliably indicate overall psychoactivity. Lisuride, which did not produce HTR, caused impaired movement, coordination, stress, cognitive disruption, and reduced prefrontal cortex EEG power. LSD, which triggered strong HTR, had minimal effects on these measures. Neither compound's effects beyond HTR depended on 5-HT₂A receptors. The HTR alone is insufficient and should be combined with other assessments.