Safety of Psychedelics: Global Data Suggests That Serious Physical Complications Resulting From Psychedelic Use Are Rare
- Jan 22
- 4 min read
The use of psychedelics and MDMA has increased in recent years, both in experimental treatments and recreational use. This study analyzed adverse event reports submitted to the WHO global database to better understand the potential real-world risks of these substances. Most reported events involved psychiatric problems related to abuse and dependence, while overdoses and pregnancy complications were rare. The results suggest that, although these substances present a relatively favorable safety profile, recreational use and combined use with other drugs may increase significant risks.
In recent years, the use of classic psychedelics and MDMA has increased in both clinical and recreational settings. Substances that were heavily stigmatized for decades have begun to receive considerable scientific and media attention due to their potential to improve mood, well-being, and treat psychiatric disorders.
Classic psychedelics such as psilocybin, LSD, DMT, and mescaline act primarily by stimulating the 5-HT2A serotonergic receptor, producing intense alterations in perception, thought, and consciousness. MDMA, while frequently included in the same group, acts through different mechanisms and is more correctly classified as an entactogen.
Clinical interest in these substances has grown, especially in relation to the treatment of mood disorders and post-traumatic stress disorder (PTSD). In the case of MDMA, advanced clinical studies, supported by organizations such as MAPS, are investigating its use in combination with psychotherapy, with promising results.
However, alongside this scientific advancement, there has also been a consistent increase in the recreational use of these substances by the general population, raising concerns about safety outside of controlled clinical settings.
Population data show that the recreational use of psychedelics has increased significantly in the last two decades. In the United States, for example, the prevalence of LSD use more than doubled between the early 2000s and the late 2010s.
The use of psilocybin and other psychoactive substances has also grown rapidly, as has the availability of MDMA in non-clinical contexts. This scenario reinforces the need to better understand the potential risks associated with the use of these drugs in the real world.
Although previous studies have classified classic psychedelics and MDMA as relatively low-harm substances compared to other drugs, healthcare professionals remain cautious.
There are concerns about possible adverse psychological effects, risk of dependence, cardiovascular events associated with chronic MDMA use, and potential toxic effects from repeated use of psychedelics, especially in regimens such as microdosing. These risks tend to be lower in controlled clinical settings and higher with frequent recreational use, often combined with other substances.
To better investigate this safety profile outside of clinical trials, the authors of this study used VigiBase, the World Health Organization's (WHO) global pharmacovigilance database. This database gathers spontaneous and voluntary reports of adverse events submitted by healthcare professionals, patients, and regulatory authorities from various countries.
The aim of the study was not to calculate the actual frequency of adverse events, but to identify signs of potential risks associated with the use of classic psychedelics and MDMA in real-world contexts.
The researchers analyzed thousands of reports associated with different substances. Most records involved MDMA and LSD, while psilocybin, DMT, and mescaline had a much smaller number of notifications.
In general, the most frequently reported adverse events were of a psychiatric nature, especially related to abuse, dependence, and substance use disorders. Overdose reports were relatively rare, representing about 1% to 2% of cases, and pregnancy complications or congenital disorders were uncommon.
When comparing the data with reference substances, such as paracetamol and oxycodone, it was observed that LSD and MDMA were associated with a significantly higher probability of reports related to alcohol abuse, substance use disorder, and dependence.
These signals were stronger than those observed for oxycodone, an opioid known for its potential for dependence. However, the authors emphasize that these findings should be interpreted with caution, as the concomitant use of multiple drugs is common and the use of illicit substances tends to be underreported.
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Adverse events associated with classic psychedelics and MDMA: a real-world population-based study using the WHO pharmacovigilance database (VigiBase)
Omer A. Syed, Sean M. Nestor, Muhammad Ishrat Husain, Mark Sinyor, Fahad Alam, and Peter Giacobbe
Psychiatry Research, Volume 357, March 2026, 116929
Abstract:
Psychedelic use has greatly increased within clinical and recreational settings over recent years. While demonstrating a favorable safety profile within certain clinical populations, little empirical research has explored safety of psychedelic use within real-world samples. Using the World Health Organization (WHO) VigiBase, a comprehensive global pharmacovigilance database with voluntary spontaneous reporting of adverse events (AEs) from real-world clinical and recreational populations, we examined reports for classic psychedelics and MDMA. Most reports were made for MDMA (n = 1573) and LSD (n = 394), while psilocybin (n = 56), DMT (n = 18), and mescaline (n = 15) had fewer reports. The most common AEs for all substances were psychiatric in nature, specifically surrounding substance or drug abuse and dependence. Reports of overdose constituted 1.1 to 1.7 % of total AEs. Pregnancy-related and congenital disorders were rare. Compared to the acetaminophen control, LSD and MDMA were associated with significantly greater odds for the reported AEs of alcohol abuse (LSD: ROR=45.7, 95 % CI: 27.2 – 76.9; MDMA: ROR=19.2, 95 % CI: 12.2 – 30.4), substance use disorder (LSD: ROR=71.1, 95 % CI: 36.3 – 139.2; MDMA: ROR=129.9, 95 % CI: 78.4 – 215.5) and substance dependence (LSD: ROR=215.1, 95 % CI: 69.0 – 670.3; MDMA: ROR=76.8, 95 % CI: 25.5 – 231.8). These reports were also greater than those associated with the external positive control, oxycodone. Taken together, this exploratory study provides the first analysis of AEs associated with psychedelics reported to a global pharmacovigilance database and can inform their real-world safety. Findings should be considered in light of limitations surrounding co-use of other substances and potential deterrence towards reporting use of illicit substances.
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