Subanesthetic ketamine for reducing the harm of cocaine use disorder

Subanesthetic ketamine offers promising potential for reducing harm in individuals with cocaine use disorder (CUD). Research indicates that even a single dose can lessen cravings and decrease drug-seeking behaviors, though achieving long-term abstinence remains challenging. However, reduced cocaine consumption itself is a meaningful outcome. Ketamine’s potential in reducing the harm of CUD is also supported by its mechanism of action in the dopaminergic system, as it counters cocaine’s effect by interacting with dopamine receptors, stabilizing brain-derived neurotrophic factor levels, and modulating lateral habenula neuron bursting. In addition, concerns about ketamine’s abuse potential are minimized when it is administered in a clinical setting under professional supervision. This is supported by its success as a treatment for depression, indicating that, with appropriate safeguards, ketamine could be a valuable pharmacological strategy for harm reduction in CUD. When developing ketamine as a CUD harm-reduction strategy, it is also important to account for sex differences, which may affect patients’ sensitivity to ketamine and the potential for misuse. Although the promising effects of ketamine in treating depression support its use for CUD, most studies have focused on depression models, and additional research is needed to confirm safety and understand its specific mechanisms in CUD. Nonetheless, subanesthetic ketamine is a promising CUD intervention and should be further explored to provide an efficient and safe solution for patients in need. This narrative review mainly elucidates the ongoing research regarding ketamine’s mechanisms of action, pharmacology, and clinical application potential in CUD.