Combined Neuromodulation and Behavioral Treatment Algorithm Development for Stimulant Use Disorder (StUD) Enriched for Vulnerable Phenotype (U01 Clinical Trial Required)

Funding Opportunity RFA-DA-25-057 from the NIH Guide for Grants and Contracts. Stimulant Use Disorder still does not have FDA- approved treatments. Neuromodulation, such as, for example, transcranial magnetic stimulation (TMC) has been successfully used for more than 10 years in major depressive disorder (MDD) where patients have failed one antidepressant and since 2018 it has been used for obsessive-compulsive disorder (OCD). Another example is transcranial direct current stimulation (tDCS) which is currently being developed for a range of mental and neurological conditions, and some of them have direct relevance for StUD vulnerable phenotype (cognitive dysfunction, compulsive, and impulsive traits). Other neuromodulation technologies potentially can also be applied to StUD. As not everyone who takes drugs becomes addicted, and while the StUD population's extreme heterogeneity represents a barrier to effective treatment development, there is a treatment gap that needs to be filled, especially for the high-risk vulnerable phenotype with low executive function and difficulties with response regulation - anxious-impulsive traits. Developing neuromodulation combined with behavioral treatment modalities (CBT, mindfulness-based approaches) that will help to maintain use decrease and prevent relapse would have tremendous value as a treatment option. Randomized controlled trials are needed to develop the treatment algorithms and to select the most efficacious one.