NfL and GFAP quantification and associations with mental health in recreational cannabis users-Results from the Swiss study on recreational cannabis access via pharmacies.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers for neuroaxonal damage and astroglial injury, respectively. The present study aimed to quantify NfL and GFAP as well as investigate their association with psychiatric symptoms in a sample of recreational cannabis users. Blood samples from 331 individuals with regular recreational cannabis use were collected. Serum NfL (sNfL) and GFAP (sGFAP) levels were quantified in duplicate by an ultrasensitive single-molecule array (Simoa) technology. Reference populations were used to calculate age-, BMI-, and (for GFAP) sex-adjusted Z scores. Participants completed validated psychometric instruments assessing symptoms of cannabis use disorder, alcohol use disorder, psychosis, depression, and anxiety. Mean GFAP levels were significantly lower than those in the reference population (t(330) = -6.718, p < 0.001), whereas NfL levels did not differ (t(330) = 1.3, p = 0.19). Participants with hazardous cannabis use and those screening positive for psychotic symptoms showed higher NfL levels. Psychotic symptoms were additionally associated with lower GFAP levels. NfL correlated positively with total Cannabis Use Disorder Identification Test-Revised (CUDIT-R) scores (ρ(329) = 0.12, p = 0.03) and specifically with the items "memory/concentration problems" (ρ(329) = 0.11, p = 0.04) and "time spent buying/using/recovering" (ρ(329) = 0.13, p = 0.02). In multiple regression analysis, psychotic and cannabis use disorder symptoms independently predicted higher NfL levels. No variables predicted GFAP levels. There was no association between self-reported cannabis use amount or frequency in the past 30 days and GFAP or NfL. The results provide preliminary evidence of cannabis-related neuroaxonal alterations, warranting longitudinal studies to clarify the temporal relationship between these biomarkers and cannabis use.