Do classic psychedelics increase the risk of seizures? A scoping review

Seizures are a concerning adverse event frequently associated with the use of psychedelics, and hence, studies involving these substances tend to exclude patients with past history of epilepsy. This is especially relevant because epileptic seizures are markedly increased in the population suffering from mental disorders, and psychedelic assisted therapy is being researched as a promising treatment for several of them. To determine the extent of the current literature on the relationship between classic psychedelics and seizures, a scoping review was performed using the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). The search was conducted in PubMed, Web of Science, Google scholar, LILACS and Scielo, and both animal and human models were included. A total of 16 publications on humans, and 11 on animals, were found. The results are heterogeneous, but globally suggest that psychedelics may not increase the risk of seizures in healthy individuals or animals in the absence of other drugs. However, concomitant use of other substances or drugs, such as kambo or lithium, could increase the risk of seizures. Additionally, these conclusions are drawn from data lacking sufficient external validity, so they should be interpreted with caution. Future paths for research and a summary on possible neurobiological underpinnings that might clarify the relationship between classical psychedelics and seizures are also provided.