Key Points
- Researchers have published initial results from a clinical trial using focused ultrasound neuromodulation for the treatment of opioid use disorder.
- The intervention significantly reduced substance cravings, and most participants did not use opioids or other substances during the 90-day follow-up period.
The research team at the WVU Rockefeller Neuroscience Institute (RNI) led by Ali Rezai, MD, executive chair of the RNI, has published initial results from its prospective, single-arm, open-label clinical trial (NCT04197921) investigating the use of low-intensity focused ultrasound (LIFU) neuromodulation for the treatment of severe opioid use disorder with co-occurring non-opioid substance use disorders. In 2017, the United States declared the opioid crisis to be a public health emergency. New treatments are critically needed to relieve cravings, relieve withdrawal symptoms, block the euphoric effects of opioids, and prevent overdose and death.
Focused Ultrasound Neuromodulation: Exploring a Novel Treatment for Severe Opioid Use Disorder
Study Population
Six men and two women with a median age of 35.5 (range 23–48) years were enrolled between February and November of 2023. The group had a median 14.1-year (range 4–36 years) and 14.9-year (range 1–37 years) history of heroin/fentanyl and prescription opioid use, respectively.
Focused Ultrasound Intervention
Each participant received 20 minutes of LIFU neuromodulation applied simultaneously to the bilateral nucleus accumbens (NAc). The MR-guided procedure was performed with Insightec’s ExAblate Neuro Type 2 (220 kHz) focused ultrasound device. A previous pilot study focused on the safety, feasibility, and dose response (Mahoney et al, 2023). Researchers assessed adverse events to determine the safety, tolerability, and feasibility of the procedure along with the impact on substance craving, substance use, mood, and anatomic and functional MRI, at 1-, 7-, 30-, 60-, and 90 days after the treatment.
Positive Results
Initial results showed the bilateral NAc LIFU neuromodulation to be safe, well-tolerated, and feasible for this treatment group. There was a significant decrease (mean 91%) in opioid craving that extended to 90 days post procedure and similar reductions in non-opioid substance craving. Five of the eight participants (62.5%) abstained from all illicit substance use throughout the 90-day follow-up (per urine toxicology tests). Resting state functional MRI scans demonstrated significantly decreased connectivity in the brains of participants who remained abstinent, specifically from the NAc to various regions of the frontal lobes, suggesting that focused ultrasound can modulate the relationship between the reward and executive/cognitive control networks.
Next Steps
The authors concluded that larger, sham-controlled, randomized studies are warranted, and the team at RNI/WVU has initiated this trial with an intended sample size of 30 participants. In parallel, the open-label trial will soon be expanded to additional enrollment sites.
“LIFU neuromodulation is an outpatient procedure that can precisely target and modulate deep brain structures implicated in addiction,” said Dr. Rezai. “Having another method for reducing substance cravings and use holds promise for patients with opioid use disorder as well as those using substances such as methamphetamine and cocaine which do not yet have any medication treatment options available.”
“These results are very promising and demonstrate the strong potential of focused ultrasound neuromodulation for addiction. Additional well-designed, and controlled studies are necessary – such as the currently ongoing randomized trial. Our findings must be replicated at other institutions so we can continue to refine the treatment and optimize outcomes for those in need,” said James Mahoney, PhD, director of addictions neuromodulation research at the RNI and co-investigator.
Funding
Funding for this clinical trial was provided by National Institute of Drug Abuse’s HEAL (Helping to End Addiction Long-term) Initiative – a part of the National Institutes of Health, WVU Rockefeller Neuroscience Institute, and the Harry T. Mangurian, Jr. Foundation.
See Biological Psychiatry (Open Access)
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