Cocaine Use Disorder: Neuropathology and Exploratory Treatments

Rationale: Abstract: Cocaine use disorder (CUD) is a clinically recognized condition characterized by compulsive drug-seeking behavior and neurobiological dysfunction. It results from complex interactions between neurotransmitter imbalances and neuroinflammatory processes. Given the growing understanding of its immunopathological effects, it is crucial to investigate the diverse mechanisms of CUD and assess new therapeutic approaches that target both neurochemical and inflammatory pathways. Objectives: The main aim of this review is to gather information on the psychopharmacological mechanisms, neuroinflammatory features, and impact of cocaine hydrochloride on neurotransmitters, especially monoamines involved in CUD. Methods: As the Food and Drug Administration has not approved any drugs for the treatment of CUD, we reviewed novel therapeutic agents and emerging treatment strategies for CUD from preclinical studies. We analyzed the current literature on CUD, focusing on its pathophysiology, neuroinflammation, and treatment. Relevant studies were sourced from PubMed, NCBI, AccessMedicine, and Clinical Key databases. Results: Preclinical findings have suggested potentially promising treatments for CUD, including L-DOPA, M. pruriens, monoamine precursors, TA-CD (cocaine vaccine), and immunotherapy. In addition, these treatment modalities have had some success in subjects given their effects on targeting neuroinflammation. Conclusions: Targeting neuroinflammation with drugs and other modalities with specific therapeutic approaches may hold promise for treating patients with CUD. However, further research is needed as no FDA-approved treatment is yet available. These novel approaches may help reduce incidence rates within the CUD patient population and should be investigated further.