Cardiac Consequences Associated with Psychedelic Use: A Systematic Review of Lysergic Acid Diethylamide, 3,4-Methylenedioxymethamphetamine, and 5-Hydroxytryptamine 2B-Mediated Valvular Heart Disease.
Tianyi Xu, Sabrina Wong, Gia Han Le, Christine E. Dri, Kayla M Teopiz, Andy Lu, Serene Lee, Taeho Greg Rhee, Liyang Yin, Stavroula Bargiota, Roger Ho, Roger S McIntyre
Pharmacopsychiatry February 5, 2026 DOI: 10.1055/a-2794-6487 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Topics | LSD MDMA |
| Key findings | Lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine may promote cardiac valvulopathy via 5-hydroxytryptamine 2B receptor signaling, though no clinical cases of lysergic acid diethylamide-induced valvulopathy have been reported. |
Abstract
Serotonergic psychedelics, such as lysergic acid diethylamide, and psilocybin, and the entactogen 3,4-methylenedioxymethamphetamine exhibit agonist activity at the 5-hydroxytryptamine 2B receptor, a signalling pathway known to mechanistically mediate drug-induced valvular heart disease. This systematic review evaluates whether chronic or repeated use of psychedelics and 3,4-methylenedioxymethamphetamine may contribute to valvular heart disease through sustained 5-hydroxytryptamine 2B receptor activation. A systematic search of Google Scholar, OVID and PubMed was conducted from inception to June 1, 2025. We sought to include studies that reported an association between psychedelics or 3,4-methylenedioxymethamphetamine at 5-hydroxytryptamine 2B binding and molecular, cellular, structural, and/or functional evidence of cardiac valvulopathy. Seventeen studies were included in this review. No studies were found on psilocybin, dimethyltryptamine or mescaline. Both lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine have high affinity for 5-hydroxytryptamine 2B receptors and promote downstream signaling linked to mitogenic and fibrotic changes in valvular tissue. In vitro and structural studies show that lysergic acid diethylamide exhibits high affinity and induces β-arrestin-biased signaling in valvular interstitial cells, while 3,4-methylenedioxymethamphetamine displays moderate affinity and similar functional responses. In vivo studies confirm serotonin-induced valvulopathy, and chronic 3,4-methylenedioxymethamphetamine use has been associated with valvular abnormalities in humans. No clinical cases of lysergic acid diethylamide-induced valvulopathy have been reported, but preclinical data support its potential to engage fibrotic signaling pathways under sustained exposure. Preliminary converging mechanistic and preclinical evidence suggests that lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine may promote cardiac valvulopathy via 5-hydroxytryptamine 2B receptor signalling. This is consistent with existing Food and Drug Administration concerns and supports the need for ongoing cardiac and valvular safety monitoring in psychedelic research.
Comparable studies
Other systematic reviews and meta-analyses on LSD, most cited first.
Citations in the library
Cites 15
- Crystal structure of an LSD-bound human serotonin receptor Cell January 26, 2017
- Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD. Neuron October 5, 2022
- Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression CNS Drugs November 17, 2021
- Mescaline: The forgotten psychedelic Neuropharmacology October 14, 2022
- Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated Frontiers in Psychiatry March 25, 2022
and 10 more in the library