The risk of chronic psychedelic and MDMA microdosing for valvular heart disease
This review (2023) covers in vitro, animal, and clinical studies to assess the potential risk of valvular heart disease (VHD) from microdosing psychedelic substances, focusing on LSD, psilocybin, mescaline, DMT, and MDMA due to their interaction with the serotonin 5-HT2B receptor. Findings show that all these compounds, except mescaline (due to low potency), were partial agonists at the 5-HT2B receptor. While safety margins from typical microdoses were greater than known valvulopathogens, there remains a potential risk. No studies directly evaluated VHD risk for the four psychedelics, but some evidence suggests chronic ingestion of full doses of MDMA might be linked to VHD.
Authors
- Tagen, M.
- Mantuani, D.
- Van Heerden, L.
Published
Abstract
Psychedelic microdosing is the practice of taking very low doses of psychedelic substances, typically over a longer period of time. The long-term safety of chronic microdosing is relatively uncharacterized, but valvular heart disease (VHD) has been proposed as a potential risk due to activation of the serotonin 5-HT2B receptor. However, this risk has not yet been comprehensively assessed. This analysis searched for all relevant in vitro, animal, and clinical studies related to the VHD risk of lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT), and the non-psychedelic 3,4-methylenedioxymethamphetamine (MDMA). All five compounds and some metabolites could bind to the 5-HT2B receptor with potency equal to or greater than that of the 5-HT2A receptor, the primary target of psychedelics. All compounds were partial agonists at the 5-HT2B receptor with the exception of mescaline, which could not be adequately assessed due to low potency. Safety margins relative to the maximum plasma concentrations from typical microdoses were greater than known valvulopathogens, but not without potential risk. No animal or clinical studies appropriately designed to evaluate VHD risk were found for the four psychedelics. However, there is some clinical evidence that chronic ingestion of full doses of MDMA is associated with VHD. We conclude that VHD is a potential risk with chronic psychedelic microdosing, but further studies are necessary to better define this risk.
Research Summary of 'The risk of chronic psychedelic and MDMA microdosing for valvular heart disease'
Introduction
Tagen and colleagues introduce the practice of psychedelic microdosing—regular use of sub-hallucinogenic doses of psychedelic substances—and note that its long-term safety is poorly characterised. Surveys indicate that microdoses are typically around 5–10% of a full psychedelic dose and are used for diverse goals such as improving mood, cognition, or creativity. Most clinical research has evaluated single or short courses of full doses, and observational surveys predominate for microdosing; neither approach reliably addresses rare or delayed adverse outcomes. The authors focus on valvular heart disease (VHD) as a theoretically plausible and serious long-term risk of chronic microdosing because drug-induced VHD has previously been linked to agonism at the serotonin 5-HT2B receptor. This review aims to assess available in vitro, animal, and clinical data on the 5-HT2B activity and VHD risk of five commonly microdosed compounds—LSD, psilocybin (psilocin), mescaline, DMT, and MDMA—and to apply established risk-assessment strategies to those data to determine what is known and what remains uncertain.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Study Details
- Study Typemeta
- Journal
- Compounds
- Topics
- APA Citation
Tagen, M., Mantuani, D., van Heerden, L., Holstein, A., Klumpers, L. E., & Knowles, R. (2023). The risk of chronic psychedelic and MDMA microdosing for valvular heart disease. Journal of Psychopharmacology, 37(9), 876-890. https://doi.org/10.1177/02698811231190865
References (49)
Papers cited by this study that are also in Blossom
Anderson, T., Petranker, R., Rosenbaum, D. et al. · Psychopharmacology (2019)
Barbosa, P., Mizumoto, S., Bogenschutz, M. P. et al. · Drug Testing and Analysis (2012)
Barker, S. A. · Psychopharmacology (2022)
Bershad, A. K., Preller, K. H., Lee, R. et al. · Biological Psychiatry (2020)
Bershad, A. K., Schepers, S. T., Bremmer, M. P. et al. · Biological Psychiatry (2019)
Bonson, K. R. · Psychopharmacology (2017)
Breeksema, J. J., Kuin, B. W., Kamphuis, J. et al. · Journal of Psychopharmacology (2022)
Brown, R. T., Nicholas, C. R., Cozzi, N. V. et al. · Clinical Pharmacokinetics (2017)
Cameron, L. P., Benson, C. J., Defelice, B. C. et al. · ACS Chemical Neuroscience (2019)
Cavanna, F., Muller, S., de la Fuente, L. A. et al. · Translational Psychiatry (2022)
Show all 49 referencesShow fewer
de Wit, H., Molla, H. M., Bershad, A. K. et al. · Addiction Biology (2022)
Dunlap, L. E., Andrews, A. M. · ACS Chemical Neuroscience (2018)
Fadiman, J., Korb, S. · Journal of Psychoactive Drugs (2019)
Family, N., Maillet, E. L., Williams, L. T. J. et al. · Psychopharmacology (2019)
Good, M., Joel, Z., Benway, T. et al. · European Journal of Pharmacology (2022)
Halberstadt, A. L., Geyer, M. A. · Neuropharmacology (2011)
Halpern, J. H., Sherwood, A. R., Hudson, J. I. et al. · Biological Psychiatry (2005)
Holze, F., Duthaler, U., Vizeli, P. et al. · British Journal of Clinical Pharmacology (2019)
Holze, F., Ley, L., Müller, F. et al. · Neuropsychopharmacology (2022)
Zhang, D. Z., Holze, F., Liechti, M. E. et al. · Clinical Pharmacology and Therapeutics (2020)
Barr, A. M., Huang, J., Pham, M. et al. · Frontiers in Psychiatry (2022)
Hutten, N. P. W., Mason, N. L., Dolder, P. C. et al. · International Journal of Neuropsychopharmacology (2019)
Hutten, N. R. P. W., Mason, N. L., Dolder, P. C. et al. · European Neuropsychopharmacology (2020)
Kaertner, L. S., Steinborn, M. B., Kettner, H. et al. · Scientific Reports (2021)
Klein, A. K., Chatha, M., Laskowski, L. J. et al. · ACS Pharmacology and Translational Science (2020)
Kolaczynska, K. E., Luethi, D., Trachsel, D. et al. · Frontiers in Pharmacology (2022)
Kuypers, K. P. C., Erritzoe, D., Knudsen, G. M. et al. · Journal of Psychopharmacology (2019)
Lea, T., Amada, N., Jungaberle, H. et al. · International Journal of Drug Policy (2020)
Lea, T., Jungaberle, H., Schecke, H. et al. · Psychopharmacology (2020)
Ley, L., Holze, F., Arikci, D. et al. · Neuropsychopharmacology (2023)
Luethi, D., Hoener, M. C., Krähenbühl, S. et al. · Biochemical Pharmacology (2019)
Marschall, J., Fejer, G., Lempe, P. et al. · Journal of Psychopharmacology (2021)
Perry, C. M., Malina, M. · Psychopharmacology (2021)
Polito, V., Stevenson, R. J. · PLOS ONE (2019)
Preller, K. H., Herdener, M., Pokorny, T. et al. · Current Biology (2017)
Prochazkova, L., Lippelt, D. P., Colzato, L. S. et al. · Psychopharmacology (2018)
Ramaekers, J. G., Mallaroni, P., Kloft, L. et al. · Journal of Cognitive Neuroscience (2023)
Ray, T. S. · PLOS ONE (2010)
Rickli, A., Luethi, D., Reinisch, J. et al. · Neuropharmacology (2015)
Rickli, A., Moning, O. D., Hoener, M. C. et al. · European Neuropsychopharmacology (2016)
Rootman, J. M., Kryskow, P., Harvey, K. et al. · Scientific Reports (2021)
Rosenbaum, D., Weissman, C. R., Anderson, T. et al. · Journal of Psychopharmacology (2020)
Studerus, E., Gamma, A., Vollenweider, F. X. · PLOS ONE (2010)
Timmermann, C., Roseman, L., Schartner, M. et al. · Scientific Reports (2019)
Van Elk, M., Fejer, G., Lempe, P. et al. · Psychopharmacology (2021)
Vogt, S. B., Ley, L., Erne, L. et al. · Translational Psychiatry (2023)
Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)
Wacker, D., Wang, S., Mccorvy, J. D. et al. · Cell (2017)
Yanakieva, S., Polychroni, N., Family, N. et al. · Psychopharmacology (2018)
Cited By (4)
Papers in Blossom that reference this study
Effinger, D. P., Schalk, S. S., King, J. L. et al. · ACS Pharmacology and Translational Science (2025)
Polito, V., Liknaitzky, P. · Journal of Psychopharmacology (2024)
Neumann, J., Dhein, S., Kirchhefer, U. et al. · Frontiers in Pharmacology (2024)
Rouaud, A., Calder, A. E., Hasler, G. · Journal of Psychopharmacology (2024)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.