Cardiovascular safety of psychedelic medicine: current status and future directions

Abstract

Psychedelics are powerful psychoactive substances that alter perception and mood processes. Their effectiveness in the treatment of psychiatric diseases was known before their prohibition. An increasing number of recent studies, due to the indisputable resurgence of serotonergic hallucinogens, have shown their efficacy in alleviating depression, anxiety, substance abuse therapies, and existential distress treatment in patients facing life-threatening illness. Psychedelics are generally considered to be physiologically safe with low toxicity and low addictive potential. However, their agonism at serotonergic receptors should be considered in the context of possible serotonin-related cardiotoxicity (5-HT2A/2B and 5-HT4 receptors), influence on platelet aggregation (5-HT2A receptor), and their proarrhythmic potential. The use of psychedelics has also been associated with significant sympathomimetic effects in both experimental and clinical studies. Therefore, the present review aims to provide a critical discussion of the cardiovascular safety of psilocybin, d-lysergic acid diethylamide (LSD), N,N-dimethyltryptamine, ayahuasca, and mescaline, based on the results of experimental research and clinical trials in humans. Experimental studies provide inconsistent information on the potential cardiovascular effects and toxicity of psychedelics. Data from clinical trials point to the relative cardiovascular safety of psychedelic-assisted therapies in the population of “healthy” volunteers. However, there is insufficient evidence from therapies carried out with microdoses of psychedelics, and there is still a lack of data on the safety of psychedelics in the population of patients with cardiovascular disease. Therefore, the exact determination of the cardiovascular safety of psychedelic therapies (especially long-term therapies) requires further research.

Developing an Ethics and Policy Framework for Psychedelic Clinical Care: A Consensus Statement

“…This presents a tension during the informed consent process. Physicians should discuss the possibility that the patient will experience personality changes and could have a transformative or self-transcendent experience and its clinical implications, while also addressing the potential risks, including long-term distress, worsening psychiatric symptoms, and cardiovascular effects, especially for patients with a personal or family history of psychosis or taking contraindicated medications, and the potential disappointment a patient might experience if they do not respond as expected. It is widely accepted that set (the mindset and expectations of those taking psychedelic medicines) and setting (the physical and cultural context in which the medicines are taken) play a clinically meaningful role in determining the content and outcomes of a psychedelic experience .…”