Effects of hallucinogenic drugs on the human heart
This review summarises evidence that classic hallucinogens (bufotenin, psilocin/psilocybin, LSD, ergotamine/ergometrine, DMT and 5‑MeO‑DMT) act via cardiac 5‑HT receptors to produce positive inotropic and chronotropic effects in humans, increasing contractile force and heart rate and potentially provoking arrhythmias. It highlights these cardiovascular actions as an under‑appreciated risk of hallucinogen use.
Authors
- Neumann, J.
- Dhein, S.
- Kirchhefer, U.
Published
Abstract
Hallucinogenic drugs are used because they have effects on the central nervous system. Their hallucinogenic effects probably occur via stimulation of serotonin receptors, namely, 5-HT2A-serotonin receptors in the brain. However, a close study reveals that they also act on the heart, possibly increasing the force of contraction and beating rate and may lead to arrhythmias. Here, we will review the inotropic and chronotropic actions of bufotenin, psilocin, psilocybin, lysergic acid diethylamide (LSD), ergotamine, ergometrine, N,N-dimethyltryptamine, and 5-methoxy-N,N-dimethyltryptamine in the human heart.
Research Summary of 'Effects of hallucinogenic drugs on the human heart'
Introduction
Neumann and colleagues frame this review around a group of structurally related tryptamine-derived hallucinogenic compounds: bufotenin, psilocin, psilocybin, lysergic acid diethylamide (LSD), ergotamine, ergometrine, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). These molecules resemble serotonin (5-HT) and therefore interact with cardiac serotonin and histamine receptors. Earlier work shows that, in humans, 5-HT increases cardiac force and rate primarily via 5-HT4 receptors rather than the 5-HT2A/3 subtypes that mediate effects in some other species; histamine acts via H2 receptors. Species differences in receptor expression complicate extrapolation from common laboratory animals to human cardiac physiology. This paper aims to consolidate available evidence on the inotropic (force) and chronotropic (rate) effects of the listed hallucinogens on the mammalian, and specifically the human, heart. Neumann and colleagues present mechanistic considerations (receptor binding and intracellular cAMP/PKA signalling), animal and transgenic mouse data, isolated human tissue experiments, clinical pharmacokinetics and small human studies, and case reports to identify potential cardiac risks and therapeutic countermeasures when these agents are used clinically or recreationally.
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Neumann, J., Dhein, S., Kirchhefer, U., Hofmann, B., & Gergs, U. (2024). Effects of hallucinogenic drugs on the human heart. Frontiers in Pharmacology, 15. https://doi.org/10.3389/fphar.2024.1334218
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