Contingency management plus deep transcranial magnetic stimulation for the treatment of cocaine use disorder: Protocol of a randomized controlled trial

Background Contingency Management (CM) is the most effective behavioral treatment for cocaine use disorder (CUD), with early response strongly predicting sustained abstinence. However, a substantial subset of individuals fail to respond. A logical next step is to augment CM with an intervention that targets relevant neural circuits. Using a staged design, this study will test whether adding deep transcranial magnetic stimulation (TMS) to lateral prefrontal and insular regions improves outcomes among CM non-responders.Methods and analysis This randomized, double-blind, sham-controlled trial will enroll 100 treatment-seeking adults with CUD. During Stage 1 (Weeks 1-2), all participants will receive high-magnitude CM. Initial response is defined as achieving two consecutive weeks of cocaine-negative urine samples. During Stage 2 (Weeks 3-10), participants who do not achieve abstinence will be classified as non-responders and randomized to active or sham deep TMS in addition to continued CM. The accelerated TMS protocol will include three sessions of intermittent theta burst stimulation delivered three times weekly for six weeks, followed by weekly sessions for two weeks. Primary analyses will evaluate the effects of CM + TMS on cocaine abstinence, reduced use, and craving among CM non-responders. Secondary analyses will examine mechanistic targets, including changes in anterior insular-amygdala connectivity and NIDA Phenotyping Assessment Battery domains of cognition, reward, and negative emotionality. Analyses will use intention-to-treat generalized linear modeling under both frequentist and Bayesian frameworks.Declaration of competing interest This trial may advance mechanistic insights and inform clinical strategies to improve outcomes for individuals with resistant CUD.Clinicaltrials gov Identifier NCT07490600.