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Review
. 2024 Feb 2:15:1334218.
doi: 10.3389/fphar.2024.1334218. eCollection 2024.

Effects of hallucinogenic drugs on the human heart

Joachim Neumann  1 , Stefan Dhein  2 , Uwe Kirchhefer  3 , Britt Hofmann  1 , Ulrich Gergs  1
Affiliations
Review

Effects of hallucinogenic drugs on the human heart

Joachim Neumann et al. Front Pharmacol. .

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.

Keywords: LSD; N,N-dimethyltryptamine; bufotenin; ergometrine; ergotamine; psilocin; psilocybin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) Structural formulae of tryptamine derived hallucinogenic compounds. (B) Schematic drawing of the proposed signalling of hallucinogenic compounds in cardiac myocytes. Ca2+ enters the mammalian heart cell via the L-type Ca2+ channel (LTCC). This process can be enhanced by hallucinogenic compounds via a cascade starting in the sarcolemma via stimulation of Gs-protein (Gs)-coupled 5-HT4 serotonin or H2 histamine receptors. Activation of adenylyl cyclase (AC) elevates subsequent production of cAMP and thereby activates cAMP-dependent protein kinase (PKA). PKA increases cardiac force generation and relaxation by increasing the phosphorylation state (P) of the L-type calcium channel (LTCC), of phospholamban (PLB) and of the inhibitory subunit of troponin (TnI). Trigger Ca2+ initiates release of Ca2+ from the sarcoplasmic reticulum via ryanodine receptors (RYR) into the cytosol. There, Ca2+ activates myofilaments and this activation leads to increased inotropy. In diastole, Ca2+ is taken up into the sarcoplasmic reticulum via a sarcoplasmic reticulum Ca2+-ATPase (SERCA), the activity of which is enhanced due to an increased phosphorylation state of PLB.
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