A recent study published in the Journal of Psychoactive Drugs provides evidence that using hallucinogenic drugs at some point in life might be associated with a slightly higher risk of developing valvular heart disease. These findings suggest a need for continued monitoring of cardiovascular safety as psychedelics become more widely used in medicine and society.
Public interest in hallucinogens is rising rapidly across the United States. People are increasingly using substances like psilocybin and LSD for therapeutic purposes and recreational experiences. The United States Food and Drug Administration has even designated some of these drugs as breakthrough therapies for treating conditions like severe depression and anxiety.
As these substances become more common, medical professionals need a full understanding of their physical safety profile. Dr. Kevin Yang, a fourth-year psychiatry resident physician at the University of California, San Diego, led this research to explore those exact physical risks.
One specific area of medical interest is the physical structure of the human heart. Many hallucinogens interact heavily with serotonin receptors in the human body. Serotonin is a chemical messenger that helps brain cells and nerve cells communicate with one another. One specific serotonin receptor, known as the 5-HT2B receptor, is prominently found in the structural tissues of the heart.
When certain drugs activate this specific receptor for a long period of time, they can cause heart valves to stiffen and thicken. “A specific pharmacological concern caught my attention,” Yang noted. “Many hallucinogens activate serotonin 5-HT2B receptors, which are also located in the heart and can cause valvular fibrosis, the same mechanism that led to the market withdrawal of fenfluramine and pergolide after they were linked to valvular heart disease.”
Medical regulators have recently advised researchers to check if modern psychedelics carry similar heart risks. To explore this potential link, the authors analyzed data from the National Institutes of Health All of Us Research Program. This large medical initiative gathers survey responses and electronic health records from diverse populations across the country.
“Despite their theoretical concern, no epidemiological study had actually examined whether individuals who use hallucinogens show higher rates of valvular heart disease in the real world,” Yang said. “The NIH All of Us Research Program offered a rare opportunity to do that by combining self-reported drug use data with linked electronic health records, which most national surveys don’t have.”
The scientists looked at a specific group of 286,842 adults who had completed a lifestyle survey. The average age of the participants was nearly 51 years old. About 61 percent of the sample was female, and roughly 61 percent identified as White. The scientists intentionally excluded participants who had congenital heart conditions from birth.
Within this large group, 13.2 percent of participants reported using hallucinogens at some point in their lives. The lifestyle survey asked participants if they had ever used substances like LSD, psilocybin mushrooms, MDMA, ketamine, or PCP. To see who had actually developed valvular heart disease, the authors checked the participants’ electronic health records for official medical diagnoses.
Initially, the raw numbers showed that people who had used hallucinogens actually had lower rates of heart valve issues. Specifically, 3.6 percent of hallucinogen users had valvular heart disease, compared to 4.7 percent of people who had never used these drugs. However, this simple comparison did not account for other important health details, also known as confounding variables.
Confounding variables are outside factors that can distort the relationship being studied. “The reversal in direction of the association was striking,” Yang explained. “In unadjusted analyses, individuals with hallucinogen use actually had lower rates of valvular heart disease compared to non-users, but this flipped after adjusting for potential confounders such as age and other health conditions.”
The participants who used hallucinogens tended to be significantly younger than the non-users, naturally giving them fewer common heart risks. “This kind of confounding, where a ‘healthier’ demographic profile masks an underlying risk, is a good reminder of why raw prevalence comparisons can be misleading and why careful statistical adjustment matters,” Yang noted.
After putting all these outside factors on an even playing field, the models showed that lifetime hallucinogen use was actually associated with higher odds of having valvular heart disease. “The adjusted odds ratio was 1.08, meaning roughly an 8% increase in the odds of valvular heart disease among individuals with lifetime hallucinogen use, which by conventional epidemiological standards is a small effect size,” Yang said.
Interestingly, the analysis revealed an unexpected finding regarding tobacco use. Smoking at least 100 cigarettes in a lifetime was associated with slightly lower odds of having the heart condition. The authors noted that this contrasts with general medical knowledge, which associates smoking with worse cardiovascular health. They suggested that unmeasured factors or differences in how often smokers seek health care might explain this unusual data point.
When interpreting this data, the researchers advise maintaining a balanced perspective. “The main takeaway is that this study detected a modest statistical signal between lifetime hallucinogen use and higher odds of valvular heart disease,” Yang summarized. “For people using or considering hallucinogens recreationally or therapeutically, this isn’t a reason for alarm, but rather a call for more research to better understand these potential associations.”
The researchers also want the public to understand the boundaries of the available data. A major limitation is the cross-sectional design, meaning the scientists only looked at a snapshot of data from a single point in time. “First, this is a cross-sectional study and thus we cannot determine directionality or causality,” Yang cautioned.
The lifestyle survey also grouped several completely different substances into one broad category of hallucinogens. While LSD and psilocybin interact heavily with the heart’s serotonin receptors, other drugs included in the survey, like ketamine, do not. Grouping these unique drugs together might obscure the specific medical risks associated with individual substances.
“Second, our measure of hallucinogen use was a single yes/no lifetime question that grouped multiple hallucinogens together,” Yang added. “Third, this variable tells us nothing about frequency, recency, or dose. As a result of these caveats, these findings should be interpreted with caution.”
This lack of detail about frequency and dose is especially relevant given the rise of microdosing. Regular, small doses of psychedelics might keep the heart’s serotonin receptors activated on a chronic basis, a pattern that tends to increase the risk of heart valve abnormalities. The current survey data could not separate these regular users from people who simply took a single dose many years ago.
Future research will need to follow participants over a longer period of time to better understand these cardiac risks. “Our team is interested in prospective longitudinal studies to establish whether frequent or long-term use of hallucinogens such as psilocybin might be associated with valvular heart disease,” Yang said. “We are also interested in incorporating echocardiography data to allow for direct assessment of valvular structure and function, rather than relying just on EHR diagnosis codes alone.”
“It’s important to emphasize that this work was motivated by a desire to take the safety profile of hallucinogens seriously, and not to cast doubt on their therapeutic potential,” Yang said. “As both recreational and therapeutic use of these substances continue to expand, we hope this exploratory study helps prompt more rigorous research into these potential associations.”
The study, “Association Between Lifetime Hallucinogen 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.
