Early-Onset Cannabis Use, Retinal Biomarkers, and Risk for Schizophrenia Preliminary Study

Cannabis remains one of the most commonly used psychoactive substances among adolescents, with increasing prevalence of daily use during formative neurodevelopmental years. This preliminary study looks at changes in low spatial frequency contrast sensitivity perception using frequency doubling virtual reality technology (IMMAD-FDT). Early initiation of cannabis use-particularly before age 16-has been consistently linked to an elevated risk for schizophrenia and related psychotic disorders. The retina, as an extension of the central nervous system, offers a unique, non-invasive window into neural structure and function, with changes potentially detectable through contrast sensitivity chart testing, frequency doubling virtual visual field testing and optical coherence tomography structural imaging (OCT).

This project looked at six participants data obtained under an Advarra Institutional Review Board Approved protocol; Digital Marker of Marijuana Intoxication: Measure of Dysfunctional Retinal Ganglion Cell Response (Pro00038518). The project was funded through the National Institute of Health; Marijuana Intoxication: Roadside Tool for Law Enforcement to Measure Impaired Peripheral Vision 15PNIJ-22-GG-04417-RESS. The data of interest were from the IMMAD-FDT. We reviewed dosed and undosed data relative to the IMMAD-FDT normative database. IMMAD-FDT measures contrast sensitivity at low spatial frequencies using temporally modulated striped square targets. The targets are displayed in a commercially available virtually reality headset equipped with eye tracking, allowing for precise measurement of threshold contrast sensitivity in decibels. This approach is particularly sensitive to dysfunction in the magnocellular visual pathway and intrinsically photosensitive retinal ganglion cells (ipRGCs).

Of the six participants; 12 eyes, nine eyes were considered abnormal relative to the normative data base, at an undosed baseline.

Previous work demonstrates overlapping patterns of visual dysfunction and retinal remodeling in both schizophrenia and chronic cannabis use, including deficits in low spatial frequency contrast sensitivity, thinning or changes of the retinal nerve fiber layer, and alterations in retinal ganglion cell integrity. These functional and structural changes are also associated with impaired facial emotion recognition, a hallmark of social cognitive dysfunction in schizophrenia. This paper synthesizes current evidence and describes further investigation using virtual reality-based IMMAD-FDT and discusses how the preliminary findings may relate to future more controlled studies that would include OCT imaging to identify early retinal biomarkers in abstinent cannabis users, categorized by age of onset and frequency of use. Future research would relate the functional and structural findings with additional tests of emotion cognition/facial recognition. Findings could inform early risk stratification and preventative interventions for psychosis.