Editorial: Brain Mediators of the Cannabis-Prodromal Psychosis Connection

The article by Yu and Jia et al.¹ in this issue of the Journal investigates the role of a subregion of the parahippocampal gyrus called the right uncus ("hook") as a possible mediator of the known increase of psychotic-like experiences (PLEs) due to the consumption of cannabinoids (ie, cannabis).² The authors chose a pattern of plausible inference worthy of pursuit. Cannabis continues to be one of the most widely used drugs globally, only behind alcohol, caffeine, and tobacco; 188 million people used cannabis worldwide in 2017.³ In January 2019, the WHO's Expert Committee on Drug Dependence (ECDD)⁴ recommended that cannabis be no longer classified as a Schedule IV drug (its medical potential is now deemed to outweigh its abuse potential). It should be noted that cannabidiol (CBD) is a non-psychoactive component of cannabis that has medicial uses in reducing pain and inflammation, controlling epileptic seizures, and possibly even treating mental illness and addiction.⁵ As more world governments legalize cannabis for recreational use, and owing to the widening availability of higher tetrahydrocannabinol content variants of cannabis, the number of cannabis users is increasing rapidly, which in turn increases the number of people having PLEs worldwide. Schizophrenia is one of the top 15 leading causes of disability worldwide.⁶ The estimated prevalence of schizophrenia and related psychotic disorders in the United States in 2005 ranged from 0.25% to 0.64%⁷; a meta-analysis a decade later found the lifetime prevalence worldwide to be 0.48% with interquartile range 0.34% to 0.85%.⁸ The high variability of sampling domains, diagnostic criteria, data availability and analytic methods employed preclude reliable estimates of incidence and prevalence increases of schizophrenia at present.