First in the World Trial of Low Intensity Focused Ultrasound for Substance Use Disorder

Select Drug Category Polydrug (i.e. concurrent use two or more drugs)Topic Technology (e.g., mHealth)Abstract Detail Clinical - ExperimentalAbstract Category Original Research Aim We initiated an FDA clinical trial to assess the safety, tolerability, and feasibility of Low Intensity Focused Ultrasound (LIFU) applied to the nucleus accumbens (NAc) in participants with opioid and co-occurring substance use disorders (SUD). Secondary aims include evaluating the impact of LIFU on substance craving. Methods Six participants with SUDs received sham LIFU followed by active LIFU sonications targeting the NAc either sequentially (left then right NAc; Participants #1 and #2) or simultaneously (bilaterally; Participants #3-6). Safety outcomes were assessed during the procedure and throughout the 90-day follow-up. Secondary outcomes included the acute (during, and immediately following LIFU sonications) and long-term assessment (up to 90-day) of cue-induced craving using a visual analog scale (0=no craving to 10=most craving ever). Results LIFU applied to the NAc was safe and well-tolerated in all participants. Sham sonication resulted in no appreciable craving changes (p>.05). Relative to baseline craving and sham sonication, enhanced NAc LIFU acutely attenuated self-reported craving for all substances (mean reduction: >50%). Reduction in craving for the participants’ most craved drugs was sustained during follow-up (p =.004; mean±SD: baseline 5.02±2.7; follow up 0.17±0.40). Moreover, participants remained abstinent from all illicit substances, verified by urine toxicology. Conclusions This is the first investigation of LIFU targeting the NAc in individuals with SUD. The procedure was safe and well-tolerated, LIFU acutely reduced cue-induced substance craving during sonication. Unexpectedly, this dramatic reduction in craving was sustained through to long-term follow up. Prior to LIFU these participants struggled with persistent craving and were unable to maintain abstinence. While promising, NAc LIFU requires further investigation in a randomized, controlled trial with a larger cohort of participants to further establish safety, determination of optimal treatment parameters, prolonged impact on craving and other critical outcomes.