Focused Ultrasound Neuromodulation for Substance Use Disorder

Given the prevalence of substance use disorder (SUD), elevated overdose death rates, and limited approved pharmacotherapies for SUD, new treatment approaches are necessary. Neuromodulation is a potential adjunctive treatment for SUD to reduce substance use and risk factors associated with drug use recurrence, such as craving. One form of neuromodulation, focused ultrasound (FUS), has significant potential given that it is noninvasive and capable of precisely targeting subcortical structures implicated in the brain's reward circuity. Both preclinical and clinical findings support FUS as a treatment for SUD, and several ongoing or planned studies are investigating its utility further. Preclinical studies using both FUS neuromodulation and blood-brain barrier opening approaches have demonstrated that FUS reduces drug-associated reward and behaviors by modulating critical components of the reward neurocircuitry. Key preclinical evidence suggests sex differences in these modulation mechanisms. Clinical findings suggest that FUS can reduce craving and use for several substances and improve emotional/behavioral symptoms, but these findings should be interpreted with caution given the open-label design and very limited number of treated cases. Given this, sham-controlled trials in larger cohorts are necessary before any conclusions can be drawn. Expanding research to incorporate a broader range of substances and brain targets while systematically refining FUS parameters is essential to fully realize the therapeutic potential of FUS as a treatment for SUD.