Preclinical evidence indicates that cocaine exerts acute and chronic effects on astrocyte functioning, which in turn modulate cocaine-related impacts on neural integrity and brain function. However, human evidence for astrocytic involvement in cocaine users (CU) remains limited. Glial fibrillary acidic protein (GFAP) is a marker of astrocyte activation with promising clinical utility in neurological conditions, yet its relevance in the addiction field is unclear. Hence, we investigated plasma GFAP levels in chronic CU (n=41) and cocaine-naive controls (HC; n=34) at baseline and after a 4-month follow-up. GFAP was assessed alongside plasma neurofilament light chain (NfL) levels, a marker of neuroaxonal injury previously associated with cocaine use in the same sample. Contrary to our hypothesis, we found no group differences in plasma GFAP concentrations between CU and HC. Neither cross-sectional nor longitudinal associations between GFAP levels and objective indices of cocaine use (derived from hair testing) were detected. However, exploratory analyses revealed higher plasma GFAP levels among CU with recent cocaine consumption (within the last 7 days), suggesting transient astrocytic responses following acute exposure. Additionally, GFAP and NfL were positively correlated across participants, supporting their functional association. Overall, these findings suggest that while GFAP might not be chronically elevated in CU, it may exhibit transient increases related to recent cocaine use. Further research is warranted to characterize the temporal dynamics and biological significance of these glial responses.

The authors have declared no competing interest.

This study was supported by a grant from the Swiss National Science Foundation (Grant Nr. 105319_162639) to BBQ. BKS received a grant from the Coordination for the Improvement of Higher Education Personnel, CAPES, Brazil (Grant Nr.: 99999.001968/2015-07). FB received salary funding from the Swiss National Science Foundation (Grant Nr: 217637). The funders had no role in the study design, in the collection, management, analysis, and interpretation of data, in the preparation, review, and approval of the manuscript, or in the decision to submit the manuscript for publication.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Research Ethics Committee of the Canton of Zurich (BASEC ID 2016-00278 and 2021-01853). Clinical and laboratory investigations were conducted in strict accordance with the principles of the Declaration of Helsinki.

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