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Here, we explored the hypothesis that plasma levels of neurofilament light chain (NfL), a promising marker of neuroaxonal pathology, are elevated in chronic cocaine users and longitudinally associated with changes in cocaine use. Plasma NfL levels were determined using single molecule array (SIMOA) technology at baseline and at a 4-month follow-up. Substance use was subjectively assessed with an extensive interview and objectively measured via toxicological analysis of urine and 4-month hair samples. In a generalized linear model corrected for sex, age, and body mass index, NfL plasma levels were elevated in cocaine users (<jats:italic>n<\/jats:italic>=35) compared to stimulant-na\u00efve healthy controls (<jats:italic>n<\/jats:italic>=35). A positive correlation between cocaine hair concentration and NfL levels was also found. Changes in cocaine hair concentration (group analysis of increasers vs. decreasers) over the 4-month interval predicted NfL levels at follow-up, 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 neurotoxic cocaine adulterant levamisole) and NfL levels were found. Our findings demonstrate that NfL is a sensitive marker for assessing cocaine-related neuroaxonal pathology, supporting the utility of blood NfL analysis in addiction research but also suggesting the detailed assessment of substance use in neurological studies and diagnostics.<\/jats:p>","DOI":"10.1007\/s12035-023-03327-6","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T11:07:28Z","timestamp":1680260848000},"page":"3935-3944","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A Longitudinal Investigation of Blood Neurofilament Light Chain Levels in Chronic Cocaine Users"],"prefix":"10.1007","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3787-6706","authenticated-orcid":false,"given":"Francesco","family":"Bavato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Kathrin","family":"Kexel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Kluwe-Schiavon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Maceski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus R.","family":"Baumgartner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Seifritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Kuhle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris B.","family":"Quednow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"3327_CR1","doi-asserted-by":"publisher","first-page":"290","DOI":"10.3109\/00952990.2015.1044607","volume":"41","author":"MG Hall","year":"2015","unstructured":"Hall MG, Alhassoon OM, Stern MJ, Wollman SC, Kimmel CL, Perez-Figueroa A, Radua J (2015) Gray matter abnormalities in cocaine versus methamphetamine-dependent patients: a neuroimaging meta-analysis. 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