Focused Ultrasound Neuromodulation: Exploring a Novel Treatment for Severe Opioid Use Disorder.

Background: Opioid use disorder remains a critical healthcare challenge as current therapeutic strategies have limitations resulting in high recurrence and deaths. We evaluated safety and feasibility of focused ultrasound (FUS) neuromodulation to reduce substance cravings and use in severe opioid- and co-occurring substance use disorders.

Methods: This prospective, open-label, single-arm study enrolled 8 participants with severe, primary opioid use disorder with co-occurring substance use. Participants received a 20-minute session of low-intensity FUS (220 kHz) neuromodulation targeting the bilateral nucleus accumbens (NAc) with follow-up for 90-days. Outcome measures included safety, tolerability, feasibility, and effects of FUS neuromodulation by assessment of adverse events, substance craving, substance use (self-report, urine toxicology), mood, neurologic examinations, and anatomic and functional MRI, at 1-, 7-, 30-, 60, and 90- day post-FUS.

Results: No serious device-related adverse events or imaging abnormalities were observed. Following FUS, participants demonstrated immediate (p<.002) and sustained (p<.0001; mean 91%) reduction in cue-induced opioid craving with median rating on scale from 0-10: 6.9 (pre-FUS) vs. 0.6 (90-day post-FUS). Craving reductions were similar for other illicit substances (e.g., methamphetamine (p<.002), cocaine (p<.02)). Decreases in opioid and co-occurring substance use were confirmed by urine toxicology. Seven participants remained abstinent at 30-days; 5 remained abstinent throughout 90-days post-FUS. Resting-state functional MRI demonstrated decrease in connectivity from the NAc to reward and cognitive regions post-FUS.

Conclusions: NAc FUS neuromodulation is safe and a potential adjunctive treatment for reducing drug cravings and use in individuals with severe opioid- and co-occurring substance use disorders. Larger, sham-controlled, randomized studies are warranted.