{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:48:02Z","timestamp":1791668882856,"version":"4.3.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>While 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both 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 \u201cenhanced\u201d (90 W) LIFU, VAS craving ratings revealed active LIFU attenuated craving for participants\u2019 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 \u00b1 0.6 vs. 1.9 \u00b1 0.4), heroin (4.2 \u00b1 0.8 vs. 1.9 \u00b1 0.4), methamphetamine (3.2 \u00b1 0.4 vs. 0.0 \u00b1 0.0), cocaine (2.4 \u00b1 0.6 vs. 0.0 \u00b1 0.0), benzodiazepines (2.8 \u00b1 0.5 vs. 0.0 \u00b1 0.0), alcohol (6.0 \u00b1 0.7 vs. 2.7 \u00b1 0.8), and nicotine (5.6 \u00b1 1.5 vs. 3.1 \u00b1 0.7); Participant #4: alcohol (3.5 \u00b1 1.3 vs. 0.0 \u00b1 0.0) and nicotine (5.0 \u00b1 1.8 vs. 1.2 \u00b1 0.8) (all <jats:italic>p<\/jats:italic>\u2019s &amp;lt; 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2023.1211566","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T11:42:01Z","timestamp":1694778121000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":78,"title":["Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial"],"prefix":"10.3389","volume":"14","author":[{"given":"James J.","family":"Mahoney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc W.","family":"Haut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Carpenter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Ranjan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy G. Y.","family":"Thompson-Lake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Marton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanhong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padma","family":"Tirumalai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Mears","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"D\u2019Haese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor S.","family":"Finomore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally L.","family":"Hodder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali R.","family":"Rezai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"ref1","volume-title":"Provisional drug overdose death counts","author":"Ahmad","year":"2022"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1001\/archgenpsychiatry.2011.121","article-title":"Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial","volume":"68","author":"Weiss","year":"2011","journal-title":"Arch Gen Psychiatry"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.drugalcdep.2019.01.031","article-title":"Polydrug use disorders in individuals with opioid use disorder","volume":"198","author":"Hassan","year":"2019","journal-title":"Drug Alcohol Depend"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3171\/2023.4.JNS23114","article-title":"Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder","volume":"9","author":"Rezai","year":"2023","journal-title":"J Neurosurg"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"120253","DOI":"10.1016\/j.jns.2022.120253","article-title":"Deep brain stimulation for psychiatric disorders and behavioral\/cognitive-related indications: review of the literature and implications for treatment","volume":"437","author":"Mahoney","year":"2022","journal-title":"J Neurol Sci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"117149","DOI":"10.1016\/j.jns.2020.117149","article-title":"Transcranial magnetic stimulation, deep brain stimulation, and other forms of neuromodulation for substance use disorders: review of modalities and implications for treatment","volume":"418","author":"Mahoney","year":"2020","journal-title":"J Neurol Sci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1176\/appi.ajp.162.8.1403","article-title":"The neural basis of addiction: a pathology of motivation and choice","volume":"162","author":"Kalivas","year":"2005","journal-title":"Am J Psychiatry"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/npp.2009.110","article-title":"Neurocircuitry of addiction","volume":"35","author":"Koob","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/S2215-0366(16)00104-8","article-title":"Neurobiology of addiction: a neurocircuitry analysis","volume":"3","author":"Koob","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1038\/s41386-019-0565-7","article-title":"Repetitive transcranial magnetic stimulation targeting the insular cortex for reduction of heavy drinking in treatment-seeking alcohol-dependent subjects: a randomized controlled trial","volume":"45","author":"Perini","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"893833","DOI":"10.3389\/fpsyt.2022.893833","article-title":"Targeting the salience network: a Mini-review on a novel neuromodulation approach for treating alcohol use disorder","volume":"13","author":"Padula","year":"2022","journal-title":"Front Psych"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.biopsych.2021.11.020","article-title":"Repetitive transcranial magnetic stimulation in alcohol dependence: a randomized, double-blind, sham-controlled proof-of-concept trial targeting the medial prefrontal and anterior cingulate cortices","volume":"91","author":"Harel","year":"2022","journal-title":"Biol Psychiatry"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/7061420","article-title":"Deep transcranial magnetic stimulation: improved coil design and assessment of the induced fields using MIDA model","volume":"2018","author":"Samoudi","year":"2018","journal-title":"Biomed Res Int"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brs.2012.02.005","article-title":"Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs","volume":"6","author":"Deng","year":"2013","journal-title":"Brain Stimul"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1002\/mds.23800","article-title":"Diagnosis and treatment of complications related to deep brain stimulation hardware","volume":"26","author":"Baizabal Carvallo","year":"2011","journal-title":"Move. Disord. Off. J. Move. Disord. Soc."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1001\/jamaneurol.2017.3129","article-title":"A review of the current therapies, challenges, and future directions of transcranial focused ultrasound technology: advances in diagnosis and treatment","volume":"75","author":"Krishna","year":"2018","journal-title":"JAMA Neurol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1080\/14737175.2019.1635013","article-title":"Neuromodulation beyond neurostimulation for epilepsy: scope for focused ultrasound","volume":"19","author":"Ranjan","year":"2019","journal-title":"Expert Rev Neurother"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"981571","DOI":"10.3389\/fnhum.2022.981571","article-title":"A scientometric analysis of the 100 most cited articles on magnetic resonance guided focused ultrasound","volume":"16","author":"Garg","year":"2022","journal-title":"Front Hum Neurosci"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"9180","DOI":"10.1073\/pnas.2002571117","article-title":"Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound","volume":"117","author":"Rezai","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"275","DOI":"10.3171\/2022.9.JNS221565","article-title":"Focused ultrasound-mediated blood-brain barrier opening in Alzheimer's disease: long-term safety, imaging, and cognitive outcomes","volume":"139","author":"Rezai","year":"2022","journal-title":"J Neurosurg"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"825802","DOI":"10.3389\/fpsyt.2022.825802","article-title":"Low intensity focused ultrasound for non-invasive and reversible deep brain neuromodulation-a paradigm shift in psychiatric research","volume":"13","author":"Arulpragasam","year":"2022","journal-title":"Front Psych"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"620863","DOI":"10.3389\/fnins.2021.620863","article-title":"Effect of low intensity transcranial ultrasound stimulation on neuromodulation in animals and humans: an updated systematic review","volume":"15","author":"Kim","year":"2021","journal-title":"Front Neurosci"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1016\/j.neuron.2019.01.019","article-title":"Manipulation of subcortical and deep cortical activity in the primate brain using transcranial focused ultrasound stimulation","volume":"101","author":"Folloni","year":"2019","journal-title":"Neuron"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e40541","DOI":"10.7554\/eLife.40541","article-title":"Offline impact of transcranial focused ultrasound on cortical activation in primates","volume":"8","author":"Verhagen","year":"2019","journal-title":"elife"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.neuron.2019.10.030","article-title":"A basal forebrain-cingulate circuit in macaques decides it is time to act","volume":"105","author":"Khalighinejad","year":"2020","journal-title":"Neuron"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1038\/s41593-019-0375-6","article-title":"The macaque anterior cingulate cortex translates counterfactual choice value into actual behavioral change","volume":"22","author":"Fouragnan","year":"2019","journal-title":"Nat Neurosci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.npbr.2020.06.004","article-title":"A double-blind pilot study of transcranial ultrasound (TUS) as a five-day intervention: TUS mitigates worry among depressed participants","volume":"37","author":"Reznik","year":"2020","journal-title":"Neurol Psychiatry Brain Res"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.clinph.2021.12.010","article-title":"Non-invasive transcranial ultrasound stimulation for neuromodulation","volume":"135","author":"Darmani","year":"2022","journal-title":"Clin Neurophysiol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"116712","DOI":"10.1016\/j.jns.2020.116712","article-title":"Long-term treatment retention in West Virginia's comprehensive opioid addiction treatment (COAT) program","volume":"411","author":"Lander","year":"2020","journal-title":"J Neurol Sci"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"593672","DOI":"10.3389\/fnhum.2020.593672","article-title":"beta-amyloid plaque reduction in the Hippocampus after focused ultrasound-induced blood-brain barrier opening in Alzheimer's disease","volume":"14","author":"D'Haese","year":"2020","journal-title":"Front Hum Neurosci"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","article-title":"A rating scale for depression","volume":"23","author":"Hamilton","year":"1960","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1176\/appi.ajp.2011.10111704","article-title":"The Columbia-suicide severity rating scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults","volume":"168","author":"Posner","year":"2011","journal-title":"Am J Psychiatry"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2023.1211566\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T11:42:03Z","timestamp":1694778123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2023.1211566\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,15]]},"references-count":32,"alternative-id":["10.3389\/fpsyt.2023.1211566"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2023.1211566","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,15]]},"article-number":"1211566"}}