If you have questions you'd like answered before you apply, feel free to book an optional call with a member of our leadership team.
.png)
Cardiovascular Safety of Psychedelics: What do we really know?
Published:
April 8, 2025
Updated:
Time to read:
8MIN
Table of Contents
Odyssey Take
This review offers critical insights into the cardiovascular safety profile of classic psychedelics, suggesting that short-term use at standard doses appears physiologically safe in healthy individuals. However, risks may emerge with high doses, chronic use, or in populations with preexisting cardiovascular conditions. The data underscore the need for systematic cardiovascular screening in psychedelic trials, especially ECG monitoring and, for 5-HT2B agonists, echocardiographic assessment of valvular function. As clinical applications expand, these findings support the integration of cardiology-informed protocols to mitigate rare but serious adverse events, particularly in real-world or repeated-use scenarios.
Title: Cardiovascular effects and safety of classic psychedelics
Summary
A recent review in Nature Cardiovascular Research examined the cardiovascular effects and safety of classic psychedelics such as psilocybin, LSD, and mescaline. Despite their therapeutic promise, especially in treating depression, PTSD, and anxiety, cardiovascular safety data have lagged behind. This comprehensive analysis breaks down known physiological effects, risk mechanisms, and gaps in current knowledge. While classic psychedelics appear largely safe at standard doses in healthy individuals, concerns remain for those with preexisting heart disease, high-dose use, or chronic exposure.
What was the goal?
The review set out to answer three critical questions:
- What cardiovascular effects do classic psychedelics have, and how are these mediated?
- Are these compounds safe for individuals with or without preexisting cardiovascular conditions?
- What are the key research gaps in assessing cardiovascular safety, particularly with chronic or repeated use?
Given the growing interest in psychedelic therapies, especially among populations with high rates of cardiovascular disease, addressing these questions is essential.
What happened in the study?
The authors conducted an in-depth literature review, focusing on clinical and preclinical data around the cardiovascular impact of classic serotonergic psychedelics.
The review covered:
- Electrophysiological effects (e.g., arrhythmia risk, QT interval changes)
- Structural effects (e.g., potential for heart valve damage via 5-HT2B receptors)
- Vascular effects (e.g., vasoconstriction, ischemia, and hypertension)
- Safety in patients with heart disease
- Interactions with serotonin receptor subtypes and signaling pathways
Key findings
Standard doses are largely safe in healthy individuals
- Mild increases in heart rate and blood pressure are common but transient.
- No serious cardiovascular events have been reported in controlled trials using standard psychedelic doses.
- The safety margins for psilocybin, LSD, and mescaline exceed those of common substances like alcohol or caffeine.
High doses and drug interactions pose greater risk
- Rare cases of cardiac arrest, arrhythmia, or ischemia have been reported, typically at high doses or in compromised individuals.
- Drug interactions, especially with monoamine oxidase inhibitors (MAOIs), can amplify cardiovascular effects.
Minimal evidence for heart valve damage—but vigilance is needed
- Psychedelics bind to 5-HT2B receptors, which are linked to valvular heart disease in other serotonergic drugs (e.g., fenfluramine, MDMA).
- No cases of psychedelic-induced valve disease have been reported, but no trials have included echocardiographic assessments.
- Functional selectivity at 5-HT2B receptors (e.g., LSD’s β-arrestin bias) could influence long-term safety.
Vascular effects vary by substance and dose
- Psychedelics can cause vasoconstriction, especially LSD at high doses.
- Reports of severe ischemic events are extremely rare but exist in the context of high/recreational doses.
Safety in individuals with cardiovascular disease is unknown
- No clinical trials to date have assessed psychedelic safety in people with preexisting CVD.
- Preclinical studies suggest potential cardioprotective effects of psilocybin mushrooms and 5-HT2A agonists like DOI in inflammatory vascular conditions.
Why is this important?
As psychedelics move toward mainstream therapeutic use, understanding their safety profile, especially cardiovascular, is critical. Many patients with mental health disorders also have underlying heart conditions. This review shows that while short-term, medically supervised psychedelic use appears safe in healthy individuals, caution is warranted for at-risk groups. The findings underscore the importance of future trials that include cardiovascular monitoring, drug interaction analysis, and long-term safety data.
Limitations
- No large-scale clinical safety trials have been conducted in patients with cardiovascular disease.
- Most studies used self-reported or indirect measures rather than objective cardiac imaging or biomarkers.
- Long-term effects of repeated or chronic psychedelic use (e.g., microdosing) remain poorly studied.
- The role of drug combinations, especially in recreational settings, adds confounding variables to case reports.
Conclusion
Classic psychedelics appear to be safe from a cardiovascular standpoint when used at standard doses in healthy individuals under supervision. However, the absence of data in populations with heart disease, and the lack of studies on chronic use, leaves critical gaps. As psychedelic research progresses, integrating rigorous cardiovascular safety assessments, including echocardiograms and ECGs, will be essential.
.svg)
