Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder

Rezai, Ali R.; Mahoney, James J.; Ranjan, Manish; Haut, Marc W.; Wang, Zheng; Lander, Laura R.; Berry, James H.; Farmer, Daniel L.; Marton, J; Tirumalai, Padma; Mears, Ashley; Thompson-Lake, Daisy G.Y.; Finomore, Victor; D’Haese, Pierre-François; Aklin, Will M.; George, David T.; Corrigan, John; Hodder, Sally

doi:10.3171/2023.4.jns23114

Cited by 4 publications

(1 citation statement)

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“…Research involving neuromodulation for SUD has recently gained momentum. Both noninvasive (e.g., repetitive transcranial magnetic stimulation [TMS] targeting the dorsolateral prefrontal cortex) and invasive (e.g., deep brain stimulation [DBS] targeting subcortical structures such as the nucleus accumbens [NAc]) forms of neuromodulation have shown potential for reducing substance craving and use in individuals with various SUDs ( 4 ). However, these neuromodulatory modalities are not without limitations ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial

Mahoney,

Haut,

Carpenter

et al. 2023

Front. Psychiatry

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IntroductionWhile current treatments for substance use disorder (SUD) are beneficial, success rates remain low and treatment outcomes are complicated by co-occurring SUDs, many of which are without available medication treatments. Research involving neuromodulation for SUD has recently gained momentum. This study evaluated two doses (60 and 90 W) of Low Intensity Focused Ultrasound (LIFU), targeting the bilateral nucleus accumbens (NAc), in individuals with SUD.MethodsFour participants (three male), who were receiving comprehensive outpatient treatment for opioid use disorder at the time of enrollment and who also had a history of excessive non-opioid substance use, completed this pilot study. After confirming eligibility, these participants received 10 min sham LIFU followed by 20 min active LIFU (10 min to left then right NAc). Outcomes were the safety, tolerability, and feasibility during the LIFU procedure and throughout the 90-day follow-up. Outcomes also included the impact of LIFU on cue-induced substance craving, assessed via Visual Analog Scale (VAS), both acutely (pre-, during and post-procedure) and during the 90-day follow-up. Daily craving ratings (without cues) were also obtained for one-week prior to and one-week following LIFU.ResultsBoth LIFU doses were safe and well-tolerated based on reported adverse events and MRI scans revealed no structural changes (0 min, 24 h, and 1-week post-procedure). For the two participants receiving “enhanced” (90 W) LIFU, VAS craving ratings revealed active LIFU attenuated craving for participants’ primary substances of choice relative to sham sonication. For these participants, reductions were also noted in daily VAS craving ratings (0 = no craving; 10 = most craving ever) across the week following LIFU relative to pre-LIFU; Participant #3 pre- vs. post-LIFU: opioids (3.6 ± 0.6 vs. 1.9 ± 0.4), heroin (4.2 ± 0.8 vs. 1.9 ± 0.4), methamphetamine (3.2 ± 0.4 vs. 0.0 ± 0.0), cocaine (2.4 ± 0.6 vs. 0.0 ± 0.0), benzodiazepines (2.8 ± 0.5 vs. 0.0 ± 0.0), alcohol (6.0 ± 0.7 vs. 2.7 ± 0.8), and nicotine (5.6 ± 1.5 vs. 3.1 ± 0.7); Participant #4: alcohol (3.5 ± 1.3 vs. 0.0 ± 0.0) and nicotine (5.0 ± 1.8 vs. 1.2 ± 0.8) (all p’s < 0.05). Furthermore, relative to screening, longitudinal reductions in cue-induced craving for several substances persisted during the 90-day post-LIFU follow-up evaluation for all participants.DiscussionIn conclusion, LIFU targeting the NAc was safe and acutely reduced substance craving during the LIFU procedure, and potentially had longer-term impact on craving reductions. While early observations are promising, NAc LIFU requires further investigation in a controlled trial to assess the impact on substance craving and ultimately substance use and relapse.

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Section: Introductionmentioning

confidence: 99%

Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial

Mahoney,

Haut,

Carpenter

et al. 2023

Front. Psychiatry

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Research Progress of DBS in the Treatment of Mental Illness

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2023

ACM

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Deep Brain Stimulation for Substance Use Disorder: Current Status

Song,

Huang,

Yang

et al. 2024

Neuropharmacology and Therapy

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Substance use disorders (SUDs) precipitate a loss of control over substance use, thus compromising daily functioning and social behavior. Current addiction treatment relies primarily on medication. Relapses may occur after extended periods of abstinence upon exposure to substance-associated stimuli or environments. More must be done to prevent relapsing. Deep brain stimulation (DBS) is used to treat a spectrum of medical conditions through insertion of electrodes into specific brain regions and administration of impulses that regulate brain activity. Considerable evidence suggests that DBS may be helpful in treating addiction, but the targets and treatment parameters remain ambiguous. This review describes research progress and the associated targets of DBS in managing alcohol, cocaine, opioid, and nicotine addiction, to lay groundwork for future research. It additionally examines the risks and safety aspects of DBS in SUD treatment, to optimize DBS for enhanced clinical efficacy in managing addictive disorders.

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Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder

Cited by 4 publications

References 20 publications

Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial

Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial

Research Progress of DBS in the Treatment of Mental Illness

Deep Brain Stimulation for Substance Use Disorder: Current Status

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