Evaluating methylphenidate as a potential treatment for cocaine use disorder: a propensity score-matched study

Background: Cocaine’s psychoactive effects arise primarily from dopamine transporter (DAT) inhibition. Prior trials suggest methylphenidate, a DAT inhibitor with pharmacologic overlap with cocaine, may reduce cocaine use, but real-world data are limited.Objectives: To evaluate whether methylphenidate exposure is associated with reduced likelihood of subsequent positive cocaine screens among veterans treated within the VA healthcare system.Methods: This retrospective cohort study used the Veterans Affairs Informatics and Computing Infrastructure (VINCI) to identify 109,608 patients with a positive cocaine screen. Among these patients 109,105 (103,535 male) had no methylphenidate exposure and 503 (458 male) were prescribed methylphenidate. Patients with methylphenidate were compared to unexposed patients and to an active comparator, bupropion. Baseline covariates included age, sex, ADHD, psychiatric and substance use disorders and comorbidities. Propensity score matching balanced groups and logistic regression models with generalized estimating equations estimated adjusted odds ratios (ORs) for a positive cocaine screen during one-year follow-up.Results: After matching, methylphenidate exposure was associated with lower odds of a follow-up positive cocaine screen compared with no exposure (OR = 0.71, 95% CI 0.51–0.98) and with bupropion (OR = 0.60, 95% CI 0.41–0.87).Conclusion: In this large real-world cohort of US veterans, methylphenidate exposure was significantly associated with a lower likelihood of subsequent cocaine detection. These results suggest that methylphenidate is a viable pharmacologic candidate for addressing cocaine use disorder, demonstrating superior outcomes in this population when compared to no exposure or the use of bupropion.