Focused Ultrasound Neuromodulation: Exploring a Novel Treatment for Severe Opioid Use Disorder
Ali Rezai, Daisy G.Y. Thompson-Lake, Pierre-François D’Haese, Nathalie Meyer, Manish Ranjan, Daniel Farmer, Victor Finomore, Jennifer L. Marton, Sally Hodder, Jeffrey Carpenter, Aniruddha Bhagwat, James Berry, Padma Tirumalai, Geoffrey Adams, Tasneem A. Arsiwala, Olaf Blanke, James J. Mahoney
Biological Psychiatry 2025, 98, 56-64 · 10.1016/j.biopsych.2025.01.001
Abstract
Background Opioid use disorder remains a critical health care challenge because current therapeutic strategies have limitations that result in high recurrence and deaths. We evaluated the 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, neurological examinations, and anatomical and functional magnetic resonance imaging (fMRI) at 1, 7, 30, 60, and 90 days post-FUS. Results No serious device-related adverse events or imaging abnormalities were observed. Following FUS, participants demonstrated immediate (p 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.
Abstract via europepmc.
Exposures
Exposure 1: Bilateral NAc FUS neuromodulation
Target: nucleus accumbens, internal capsule — “bilateral nucleus accumbens (NAc) and ventral anterior internal capsule”
Device: Insightec · Insightec · ExAblate Neuro Type 2 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 220 | ✓✓✓ |
| Pulse duration (ms) | 100 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 0.333 | ✓✓✓⚑ |
| Duty cycle (%) | 3.3pulse duration × PRF gives 3.33% | ✓✓✓ |
| Sonication duration (s) | 300 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
An initial 5-minute (300 s) zero-energy FUS session (no energy delivered) was followed by four 5-minute (300 s) block sessions of active FUS (8 subspots per target, 90-100 W therapeutic energy, 100 repetitions per subspot at an effective TR of 3 s), delivered to the bilateral NAc for up to a total of 20 minutes of active FUS. All block sessions were single-blinded (participant only).
Flags from extraction
exposures[0].timing.protocol_description— Source text reads '43 5-minute (300 seconds) block sessions', which is inconsistent with the paper's own later statement that participants were 'scheduled to complete four 5-minute block sessions for a total of 20 minutes of active FUS'; recorded protocol_description using the four-block figure and flagged the '43' as a likely OCR/typesetting error for 'four'.exposures[0].timing.pulse_repetition_frequency_hz— PRF was derived by converting the stated repetition period (TR = 3 seconds) to Hz (1/3 = 0.333 Hz); this is consistent with the stated duty cycle (100 ms / 3 s = 3.3%).n_sessions_per_subject— Most participants received a single FUS treatment, but the protocol allowed a second treatment after relapse and one participant received a second treatment; recorded as 1 (primary treatment) with this caveat.exposures[0].free_field— The paper reports acoustic power (90-100 W) but no pressure or intensity (kPa or W/cm2) values in any domain.