Novel Pharmacological Agents for the Treatment of Cocaine Use Disorder

Purpose of Review This narrative review aims to summarize the literature on novel pharmacological agents with potential for the treatment of cocaine use disorder. Recent Findings Available data on several agents suggest a broad range of neurobiological targets and mechanisms. While the mechanisms of several of these agents converge on the regulation of dopamine pathways, several other related or independent mechanisms may explain their potential benefits. For example, cholinergic agents may improve cognition, serotonergic agents like 5HT2C agonists may reduce impulsivity and anxiety, alpha-adrenergic antagonists may regulate arousal pathways, and kappa-opioid receptor, corticotropin-releasing factor, and orexin antagonists may influence stress and emotional processes. Cocaine vaccines may decrease the capacity of cocaine to reach the central nervous system and exert its impact. Although there are also several novel glutamatergic agents proposed as treatments for cocaine use disorder, they will not be included as part of this narrative review. Summary For several potentially promising agents, clinical translation has yet to be achieved. Huperzine-A, varenicline, doxazosin, nepicastat, suvorexant, and cocaine vaccines have some preclinical and clinical support. Future work should optimize the specificity of these agents as non-selectivity is often a current limitation. For agents with both preclinical and clinical support, replication and extension studies with larger samples are warranted as clinical evidence is often mixed at best.