A new analysis of global pharmacovigilance data indicates that while reports of psychiatric distress are common among users of classic psychedelics and MDMA, severe physical health complications appear to be relatively rare in real-world settings. The study suggests that the high rates of reported substance abuse associated with these drugs may be heavily influenced by the simultaneous consumption of other intoxicants rather than the psychedelics alone. These findings were published in Psychiatry Research.
The consumption of psychedelic substances has increased significantly in recent years. This rise has occurred in both clinical settings, where researchers are testing these compounds for therapeutic potential, and in unregulated recreational environments.
National surveys in the United States have documented a steady growth in the use of LSD and other hallucinogens among adults over the last two decades. While clinical trials generally indicate that these substances have a favorable safety profile, such studies are conducted under strictly controlled conditions with carefully screened participants.
Clinical trials often exclude individuals with complex medical or psychiatric histories to ensure safety and data clarity. This exclusion criteria means that data from trials may not fully represent the risks faced by the general population using these drugs in naturalistic settings. There has been a lack of empirical research exploring the safety of psychedelic use within real-world samples.
“Psychedelic use, mainly surrounding magic mushrooms (or psilocybin) and LSD, has been rapidly increasing within both recreational and academic contexts over recent years. Nevertheless, these substances may still carry some stigma and misconceptions surrounding their safety in the eyes of the public, and there has not been much research on the side effects related to real-world use of these substances,” said study author Omer A. Syed, a PhD student at the University of Toronto.
“In academic contexts, there are some supposed theoretical risks related to psychedelic use, such as cardiotoxic effects from chronic use or congenital/ developmental abnormalities following use during pregnancy or breastfeeding. However, it is often difficult to accurately and empirically assess such side effects. This study attempted to bridge this gap of real-world side effects and supposed theoretical risks.”
The research team collected data from VigiBase, which is the World Health Organization’s global individual case safety report database. This comprehensive repository aggregates spontaneous reports of adverse events from more than 180 countries. It includes data submitted by healthcare professionals, pharmaceutical companies, and consumers. The researchers accessed this data through the VigiAccess public dashboard.
The study focused on reports related to “classic” psychedelics, specifically LSD, psilocybin, DMT, and mescaline. The researchers also included MDMA in their analysis. Although MDMA is chemically distinct from classic psychedelics, it is frequently grouped with them in clinical and recreational contexts. The team examined all reports available in the database from its inception up to December 14, 2025.
The researchers identified a total of 1,573 adverse event reports for MDMA and 394 reports for LSD. The number of reports for the other substances was considerably lower. There were only 56 reports for psilocybin, 18 for DMT, and 15 for mescaline. The majority of these reports involved male individuals. The most common age group represented in the data was adults between 18 and 44 years old.
“One of the most surprising result was that while psilocybin is by far the most commonly reported psychedelic that is used according to national and global psychedelic-specific surveys, most reports in this database were for MDMA and LSD, and reports related to psilocybin and other classic psychedelics, namely DMT and mescaline, were quite low,” Syed told PsyPost.
To provide context for their findings, the researchers compared the psychedelic reports against two control substances. Acetaminophen was selected as a negative control because it has a well-established safety profile with low potential for abuse or dependence. Oxycodone was chosen as a positive control because it is known to have high potential for abuse and dependence. The researchers used a statistical tool called the Reporting Odds Ratio to compare the frequency of specific adverse events across these different substances.
The analysis revealed that the most frequent category of adverse events for all five psychedelic substances involved psychiatric disorders. Approximately 38 percent of all adverse events reported for LSD fell into this category. Similarly, psychiatric issues accounted for roughly 32 percent of the reports associated with MDMA. The second most common category involved nervous system disorders, which appeared in about 11 to 15 percent of the reports depending on the substance.
In contrast to the prevalence of psychiatric complaints, reports of physical organ damage or severe physiological distress were uncommon. Cardiac disorders, for example, made up only about 5 percent of the total adverse events reported for MDMA. This figure was even lower for LSD and the other classic psychedelics. Reports specifically citing “overdose” were also relatively rare, constituting between 1.1 percent and 1.7 percent of the total adverse events for LSD and MDMA.
The researchers also specifically investigated reports related to pregnancy and congenital development. The data showed that complications in these areas were extremely rare. For MDMA, there were nine reports related to pregnancy conditions, such as premature delivery or stillbirth. There were four reported cases of congenital disorders associated with MDMA. For LSD, there was one report of fetal growth restriction and two reports of congenital disorders. The other substances had no reports in these categories.
A significant portion of the study focused on analyzing reports of drug abuse and dependence. When compared to the acetaminophen control, both LSD and MDMA were associated with significantly higher odds of being linked to reports of “substance use disorder” and “dependence.” For instance, LSD had a Reporting Odds Ratio of 71.1 for substance use disorder compared to acetaminophen. MDMA showed an even higher ratio of 129.9.
The comparison with oxycodone yielded more complex results. As expected, oxycodone had much higher odds of being associated with “drug dependence” than either LSD or MDMA. However, the psychedelics were associated with higher odds of reports involving “alcohol abuse,” “substance abuse,” and “substance use disorder” than oxycodone. The researchers noted that “drug dependence” is a term often used for prescription medications, whereas “drug abuse” is more commonly applied to illicit substances.
The researchers argue that these findings likely reflect the common practice of “polysubstance use,” or using multiple drugs at the same time. Global surveys have consistently shown that people who use psychedelics frequently consume alcohol, cannabis, or other recreational drugs simultaneously. The high number of reports involving alcohol abuse and substance use disorder in this dataset may stem from the secondary substances consumed alongside the psychedelic.
The study identified reports categorized as “toxicity to various agents” for both MDMA and LSD. This specific categorization further suggests that other chemical agents were present and may have contributed to the adverse events. Because the VigiBase public data does not provide case-level details, the researchers could not isolate exactly which other substances were involved in each specific report. This makes it difficult to determine if the reported dependence or abuse was driven by the psychedelic or by the co-administered drugs.
The findings regarding physical safety align with existing clinical literature. The scarcity of reports regarding cardiac, respiratory, or gastrointestinal disorders supports the general consensus that classic psychedelics are physiologically well-tolerated. While concerns exist regarding potential heart risks from chronic microdosing or long-term MDMA use, such events did not appear frequently in this dataset. The low number of pregnancy-related reports may suggest that public education regarding the avoidance of psychoactive substances during pregnancy has been effective.
“Given the nuance associated with the interpretation of this study’s findings, the average person should not use this report to create a personal risk assessment or judgements for using these substances,” Syed explained. “In general, our results highlight that drug abuse and dependence is pronounced within the reports related to LSD and MDMA use, likely due to the co-use of other substances alongside psychedelics.”
“Global surveys have found those who use psychedelics do indeed use several other recreational substances as well, sometimes at the same time. Therefore, it is difficult ascertain whether our findings of heightened reports related to substance abuse and dependence are a consequence of the use of psychedelics, use of other substances, or from a synergistic combination of various substances being used at the same time.”
“Encouragingly, some of the more serious side effects such as overdose, pregnancy-related complications, congenital abnormalities, and cardiac disorders were not as commonly reported,” Syed said. “Nevertheless, people should continue to follow the current guidelines of avoiding psychedelic use while pregnant or breastfeeding, as well as avoiding use if diagnosed with a serious psychiatric, neurological, or cardiovascular condition. Perhaps there were fewer adverse reports related to these conditions, not because these aren’t valid contraindications, but because of an improved public education towards safe and responsible use.”
There are some limitations to consider. The data in VigiBase comes from voluntary reporting, which means it is subject to underreporting and inconsistency. Because classic psychedelics and MDMA remain illegal in most parts of the world, consumers may be hesitant to report adverse effects to any system that feeds into government databases. This fear of legal repercussions could mean that the actual number of adverse events is higher than what is captured here.
“Since psychedelics are illegal and controlled substances in most jurisdictions, people may be hesitant to report their side effects to these substances because that would mean admitting use to a healthcare regulatory body, which are typically government-run,” Syed noted. “Therefore, while these global reports are valuable in providing preliminary insights into side effects, this sample may not be generalizable to the entire psychedelic user population.”
The database also lacks detailed patient information. The researchers could not account for pre-existing medical conditions, dosage amounts, or the purity of the substances taken. This lack of granularity means the study can identify statistical signals and associations but cannot prove causation.
Despite these limitations, the study provides a rare glimpse into the global safety profile of these substances outside of clinical trials. The researcher conclude that while psychiatric adverse events and substance abuse reports are common, they are likely complicated by the use of other drugs. Future research will need to utilize more comprehensive datasets to further untangle the risks of psychedelics from the risks of polysubstance use.
“The overarching aim of my research is to better understand the safety and efficacy of these novel therapeutics – primarily psilocybin and the dissociative drug ketamine – for mood disorders,” Syed added. “I am also involved in investigations surrounding the microdosing of psychedelics, and aim to further investigate the safety of repeatedly consuming psychedelics at microdoses.”
The study, “Adverse events associated with classic psychedelics and MDMA: a real-world population-based study using the WHO pharmacovigilance database (VigiBase),” was authored by Omer A Syed, Sean M Nestor, Muhammad Ishrat Husain, Mark Sinyor, Fahad Alam, and Peter Giacobbe.
Leave a comment
You must be logged in to post a comment.