Recent research published in Psychotropic Drugs Journal provides evidence that using hallucinogens at some point in life may slightly increase the risk of developing valvular heart disease. These findings suggest the need for continued monitoring of cardiovascular safety as psychedelics become more widely used in medicine and society.
Public interest in hallucinogens is rapidly increasing across the United States. More and more people are using substances such as psilocybin and LSD for therapeutic purposes and recreational experiences. The U.S. Food and Drug Administration has designated some of these drugs as breakthrough therapies to treat conditions such as severe depression and anxiety.
As these substances become more common, medical professionals need to fully understand their safety profile in the body. Dr. Kevin Yang, a fourth-year psychiatry resident at the University of California, San Diego, led the study to examine these exact physical risks.
One area of medical interest is the physical structure of the human heart. Many hallucinogens interact strongly with the human body’s serotonin receptors. Serotonin is a chemical messenger that helps brain cells and nerve cells communicate with each other. One particular serotonin receptor, known as the 5-HT2B receptor, is prominent in the structural tissues of the heart.
When certain drugs activate this particular receptor for long periods of time, heart valves can become stiffer and thicker. “Certain pharmacological concerns caught my attention,” Yang said. “Many psychedelics activate serotonin 5-HT2B receptors, which are also present in the heart and can cause valvular heart disease. This is the same mechanism that was linked to valvular heart disease and led to the withdrawal of fenfluramine and pergolide from the market.”
Medical regulators recently advised researchers to see if modern psychedelics carry similar heart risks. To explore this potential link, the authors analyzed data from the National Institutes of Health’s All of Us Research Program. This large-scale health initiative collects survey responses and electronic health records from a diverse population across the country.
“Despite the theoretical concerns, no epidemiological studies have actually investigated whether people who use psychedelics have higher rates of valvular heart disease in the real world,” Yang said. “The NIH All of Us Research Program provided a unique opportunity to do this by combining self-reported drug use data with linked electronic health records, something that most national surveys do not have.”
Scientists studied a specific group of 286,842 adults who completed a lifestyle survey. The average age of the participants was approximately 51 years. Approximately 61 percent of the sample was female and approximately 61 percent identified as white. The researchers intentionally excluded participants who had congenital heart disease from birth.
Within this large group, 13.2% of participants reported using psychedelics at some point in their lives. The lifestyle survey asked participants whether they had ever used substances such as LSD, psilocybin mushrooms, MDMA, ketamine, and PCP. To confirm who actually developed valvular heart disease, the authors checked participants’ electronic health records to confirm a formal medical diagnosis.
Initially, raw numbers showed that people who had used psychedelics actually had lower rates of heart valve problems. Specifically, 3.6 percent of psychedelic drug users had valvular heart disease, compared to 4.7 percent of those who had never used psychedelics. However, this simple comparison does not take into account other important health details, also known as confounding variables.
Confounding variables are external factors that can distort the relationships being studied. “The association’s turnaround has been amazing,” Yang explained. “In unadjusted analyses, people who used psychedelics actually had lower rates of valvular heart disease than non-users, but this was reversed after adjusting for potential confounders such as age and other health conditions.”
Participants who used psychedelics tended to be significantly younger than non-users, which naturally led to fewer general heart risks. “This kind of confounding, where a ‘healthier’ demographic profile masks potential risks, is a good reminder of why raw prevalence comparisons can be misleading and why careful statistical adjustment is important,” Yang noted.
After putting all these external factors on a level playing field, the model showed that lifetime psychedelic drug use was indeed associated with higher odds of developing heart valve disease. “The adjusted odds ratio was 1.08, implying an approximately 8% increased odds of valvular heart disease among lifelong psychedelic drug users, but the effect size is small by traditional epidemiological standards,” Yang said.
Interestingly, the analysis revealed an unexpected finding regarding tobacco use. It was found that smoking at least 100 cigarettes in a lifetime was associated with a slightly lower chance of developing heart disease. The authors noted that this is in contrast to common medical wisdom that links smoking to poor cardiovascular health. They suggested that unmeasured factors or differences in the frequency with which smokers seek medical care may explain this unusual data point.
The researchers advise maintaining a balanced perspective when interpreting this data. “The main takeaway is that this study detected a modest statistical signal between lifetime psychedelic drug use and higher odds of valvular heart disease,” Yang summarized. “For those using or considering psychedelics for recreational or therapeutic purposes, this is not a reason for alarm, but rather calls for further research to better understand these potential links.”
Researchers also want the public to understand the boundaries of available data. The main limitation is the cross-sectional design, which means the scientists only looked at a snapshot of data from a single point in time. “First, this is a cross-sectional study, so we cannot determine directionality or causality,” Yang cautioned.
Lifestyle research has also classified several very different substances into one broad category: hallucinogens. LSD and psilocybin interact strongly with serotonin receptors in the heart, but other drugs included in the study, such as ketamine, do not. Grouping these unique medications can obscure the specific medical risks associated with individual substances.
“Second, our measure of psychedelic drug use was a single lifetime yes/no question that grouped multiple psychedelics,” Yang added. “Third, this variable tells us nothing about frequency, recency, or dose. Because of these caveats, these results should be interpreted with caution.”
This lack of detail regarding frequency and dosage is especially important given the rise in microdosing. Regularly taking small amounts of psychedelic drugs can keep the heart’s serotonin receptors chronically activated, and this pattern tends to increase the risk of heart valve abnormalities. Current study data could not distinguish between these regular users and those who simply took a single dose years ago.
Future studies will need to follow participants over time to better understand these cardiac risks. “Our team is interested in prospective longitudinal studies to establish whether frequent or long-term use of psychedelics, such as psilocybin, is associated with valvular heart disease,” Yang said. “We are also interested in incorporating echocardiography data to be able to directly assess valve structure and function, rather than relying solely on EHR diagnosis codes.”
“It is important to emphasize that this study is motivated by a desire to take seriously the safety profile of psychedelics and does not cast doubt on their therapeutic potential,” Yang said. “We hope that this exploratory study will help facilitate more rigorous research into these potential links as both recreational and therapeutic use of these substances continues to expand.”
The study, “The Association between Lifetime Psychedelic Drug Use and Valvular Heart Disease: Findings from the All of Us Research Program,” was authored by Kevin H. Yang, Miranda Rasmussen, Kush Bhatt, Nora Satybaldiyeva, Wayne Kepner, Alison A. Moore, and Jaclyn Bergstrom.
