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.