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

Mean serum GFAP levels in recreational cannabis users were significantly lower than those in the reference population.

• Sample consisted of 331 individuals with regular recreational cannabis use
• t(330) = -6.718, p < 0.001
• GFAP levels were adjusted for age, BMI, and sex using reference population Z scores
• Levels were quantified using ultrasensitive single-molecule array (Simoa) technology in duplicate

Serum NfL levels in recreational cannabis users did not differ significantly from the reference population overall.

• t(330) = 1.3, p = 0.19
• NfL Z scores were adjusted for age and BMI relative to reference populations
• Despite no overall group difference, subgroup analyses revealed elevated NfL in specific symptom groups

Participants with hazardous cannabis use and those screening positive for psychotic symptoms showed higher serum NfL levels.

• Both hazardous cannabis use and positive psychosis screening were associated with elevated NfL
• In multiple regression analysis, psychotic symptoms and cannabis use disorder symptoms independently predicted higher NfL levels
• No association was found between self-reported cannabis use amount or frequency in the past 30 days and NfL levels

Psychotic symptoms were associated with lower serum GFAP levels in addition to higher NfL levels.

• Psychotic symptoms were assessed using validated psychometric instruments
• No variables predicted GFAP levels in multiple regression analysis
• The association of psychotic symptoms with both higher NfL and lower GFAP represents a divergent biomarker pattern

NfL correlated positively with total Cannabis Use Disorder Identification Test-Revised (CUDIT-R) scores and specific CUDIT-R items.

• Total CUDIT-R score correlation: ρ(329) = 0.12, p = 0.03
• Specific item 'memory/concentration problems': ρ(329) = 0.11, p = 0.04
• Specific item 'time spent buying/using/recovering': ρ(329) = 0.13, p = 0.02
• These correlations were statistically significant but of small magnitude

Self-reported cannabis use amount or frequency in the past 30 days was not associated with serum GFAP or NfL levels.

• No significant association was found between recent cannabis use quantity/frequency and either biomarker
• This suggests that short-term use patterns may not directly predict biomarker levels
• Participants completed validated psychometric instruments assessing symptoms of cannabis use disorder, alcohol use disorder, psychosis, depression, and anxiety