Cannabis use and psychotic-like experiences in the All of Us Research Program

Cannabis use has been linked to psychotic-like experiences (PLEs). Amid increasing legalization, we examined the extent to which cannabis use is associated with PLEs after adjusting for other risk factors in a contemporary United States sample.

We performed a cross-sectional analysis of self-reported cannabis use and four types of self-reported PLEs (auditory and visual perceptual distortions, referential ideation, and persecutory ideation) in the population-based biobank, the All of Us Research Program release 8 (maximum analytic N = 62,153).

Cannabis ever-use (ORs = 1.21 - 1.44, p-values < 2.7e-6) and more frequent past 3-month cannabis use (within lifetime ever-users) were associated with all four PLEs (χ²(4) = 21.06 - 70.09, p-values = 3.08e-4 to 2.17e-14), and these associations remained when adjusting for personal and family history of schizophrenia and polygenic liability for schizophrenia. The schizophrenia polygenic score, but not cannabis use frequency, was correlated with greater likelihood of being prescribed medication for the PLEs. When adjusting for lifetime ever-use of other substances, cannabis ever-use was no longer associated with PLEs, while methamphetamine use, cigarette use, and opioid use were associated with PLEs (ORs = 1.22 to 1.65, p-values < 1.68e-05).

Prior associations between cannabis use and PLEs may have been confounded by comorbid use of other substances. Future studies that distinguish cannabis use from other substance use in the etiology of PLEs could provide insight into this transdiagnostic construct.