Adverse events associated with classic psychedelics and MDMA: a real-world population-based study using the WHO pharmacovigilance database (VigiBase)

Adverse event reports for classic psychedelics and MDMA in the WHO global pharmacovigilance database VigiBase show that most reports were for MDMA (1,573) and LSD (394), with fewer for psilocybin (56), DMT (18), and mescaline (15). The most common adverse events were psychiatric, particularly substance abuse and dependence. Overdose reports made up 1.1 to 1.7% of total adverse events. Pregnancy-related and congenital disorders were rare. Compared to acetaminophen, LSD and MDMA were associated with significantly greater odds of reported alcohol abuse, substance use disorder, and substance dependence, and these odds were also greater than those for oxycodone. This exploratory analysis provides a first look at real-world safety data, though findings are limited by potential underreporting and co-use of other substances.

Study at a glance

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.