A longitudinal investigation of blood neurofilament light chain levels in chronic cocaine users

Objectives To explore the hypothesis that plasma levels of neurofilament light chain (NfL), a marker of neuroaxonal pathology, are elevated in chronic cocaine users (CU) and longitudinally associated with changes in cocaine use. Methods As part of the Social Stress Cocaine Study (SSCP), we assessed 35 CU and 35 stimulant-naïve healthy controls (HC) at baseline and at a 4-month follow-up. Plasma NfL levels were determined from blood samples using single molecule array (SIMOA) technology. Substance use was subjectively assessed with an extensive interview and objectively measured via toxicological analysis of urine and 4-month hair samples. Results In a generalized linear model corrected for sex, age, and body mass index, NfL plasma levels were elevated in CU compared to HC (p<0.05). A moderate positive correlation between cocaine hair concentration and NfL levels was also found in CU (r(s)=0.36, p=0.03). Changes in cocaine hair concentration (group analysis of increasers vs. decreasers) over the 4-month interval predicted NfL levels at follow-up (p=0.002), indicating a rise in NfL with increased cocaine use and a reduction with decreased use. No associations between use or change of use of other substances (including the cocaine adulterant levamisole) and NfL levels were found (r(s)≤±0.27, p>0.05). Conclusions Our findings demonstrate that NfL is a sensitive marker for assessing cocaine-related brain pathology, supporting the utility of blood NfL analysis in addiction research. The results also suggest that cocaine use should be considered a potential confounder in diagnostic applications and clinical studies using NfL.