Download PDF
Pharmacopsychiatry
DOI: 10.1055/a-2794-6487
Review

Cardiac Consequences Associated with Psychedelic Use: A Systematic Review of Lysergic Acid Diethylamide, 3,4-Methylenedioxymethamphetamine, and 5-Hydroxytryptamine 2B-Mediated Valvular Heart Disease

Authors

  • Tianyi Xu

    1   Brain and Cognition Discovery Foundation, Toronto, Canada (Ringgold ID: RIN7938)
    2   Department of Pharmacology and Toxicology, University of Toronto- St George Campus, Toronto, Canada (Ringgold ID: RIN654596)

  • Sabrina Wong

    1   Brain and Cognition Discovery Foundation, Toronto, Canada (Ringgold ID: RIN7938)
    2   Department of Pharmacology and Toxicology, University of Toronto- St George Campus, Toronto, Canada (Ringgold ID: RIN654596)
    3   Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Canada (Ringgold ID: RIN7989)

  • Gia Han Le

    1   Brain and Cognition Discovery Foundation, Toronto, Canada (Ringgold ID: RIN7938)
    3   Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Canada (Ringgold ID: RIN7989)
    4   Institute of Medical Science, University of Toronto, Toronto, Canada (Ringgold ID: RIN686133)

  • Christine E. Dri

    1   Brain and Cognition Discovery Foundation, Toronto, Canada (Ringgold ID: RIN7938)

  • Kayla M. Teopiz

    1   Brain and Cognition Discovery Foundation, Toronto, Canada (Ringgold ID: RIN7938)
    3   Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Canada (Ringgold ID: RIN7989)
    4   Institute of Medical Science, University of Toronto, Toronto, Canada (Ringgold ID: RIN686133)

  • Andy Lu

    1   Brain and Cognition Discovery Foundation, Toronto, Canada (Ringgold ID: RIN7938)
    5   Department of Psychology, University of Western Ontario, London, Canada (Ringgold ID: RIN6221)

  • Serene Lee

    6   Department of Health Sciences, Queen’s University, Kingston, Canada (Ringgold ID: RIN4257)

  • Taeho Greg Rhee

    7   Department of Psychiatry, Yale School of Medicine, New Haven, United States (Ringgold ID: RIN12228)
    8   Department of Public Health Sciences, University of Connecticut School of Medicine, Farmington, United States (Ringgold ID: RIN12227)

  • Liyang Yin

    1   Brain and Cognition Discovery Foundation, Toronto, Canada (Ringgold ID: RIN7938)

  • Stavroula Bargiota

    9   Department of Psychiatry, University of Thessaly, Larissa, Greece (Ringgold ID: RIN393317)

  • Roger Ho

    10   Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore (Ringgold ID: RIN63751)
    11   Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore (Ringgold ID: RIN607105)
    12   Division of Life Science (LIFS), Faculty of Science, Hong Kong University of Science and Technology, Hong Kong, Hong Kong (Ringgold ID: RIN58207)

  • Roger S. McIntyre 

    2   Department of Pharmacology and Toxicology, University of Toronto- St George Campus, Toronto, Canada (Ringgold ID: RIN654596)
    13   Department of Psychiatry, University of Toronto, Toronto, Canada (Ringgold ID: RIN7938)
Further Information
Also available at
   Permissions and Reprints

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.

Keywords

Cardiovascular effects - serotonin receptors - LSD - psychedelics - MDMA


Publication History

Received: 19 July 2025

Accepted after revision: 21 January 2026

Article published online:
05 February 2026

© 2026. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany