Neuroglia in substance use disorders

Substance use disorders (SUD) remain a major public health concern in which individuals are unable to control their use of substances despite significant harm and negative consequences. Drugs of abuse dysregulate major brain and behavioral functions. Glial cells, primarily microglia and astrocytes, play a crucial role in these drug-induced molecular and behavioral changes. This review explores preclinical and clinical studies of how neuroglia and their associated neuroinflammatory responses contribute to SUD and reward-related properties. We evaluate preclinical and clinical evidence for targeting neuroglia as therapeutic interventions. In addition, we evaluate the literature on the gut microbiome and its role in SUD. Clinical treatments are most effective for reducing drug cravings, and some have yielded promising results in other measures of drug use. N-Acetylcysteine, through modulation of cysteine-glutamate antiporter of glial cells, shows encouraging results across a variety of drug classes. Neuroglia and gut microbiome interactions are important factors to consider with regard to SUD and could lead to novel therapeutic avenues. Age- and sex-dependent properties of neuroglia, gut microbiome, and drug use behaviors are important areas in need of further investigation.