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Cited by 121Transcranial Magnetic Stimulation StudiesNeurological disorders and treatmentsSubstance Abuse Treatment and Outcomes

Transcranial magnetic stimulation, deep brain stimulation, and other forms of neuromodulation for substance use disorders: Review of modalities and implications for treatment

Open access
Mahoney, James J., Hanlon, Colleen A., Marshalek, Patrick J., Rezai, Ali R., Krinke, Lothar·2020·Journal of the Neurological Sciences
DOI 10.1016/j.jns.2020.117149PMC PMC7702181
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Abstract

Given the high prevalence of individuals diagnosed with substance use disorder, along with the elevated rate of relapse following treatment initiation, investigating novel approaches and new modalities for substance use disorder treatment is of vital importance. One such approach involves neuromodulation which has been used therapeutically for neurological and psychiatric disorders and has demonstrated positive preliminary findings for the treatment of substance use disorder. The following article provides a review of several forms of neuromodulation which warrant consideration as potential treatments for substance use disorder. PubMed, PsycINFO, Ovid MEDLINE, and Web of Science were used to identify published articles and clinicaltrials.gov was used to identify currently ongoing or planned studies. Search criteria for Brain Stimulation included the following terminology: transcranial direct current stimulation, transcranial magnetic stimulation, theta burst stimulation, deep brain stimulation, vagus nerve stimulation, trigeminal nerve stimulation, percutaneous nerve field stimulation, auricular nerve stimulation, and low intensity focused ultrasound. Search criteria for Addiction included the following terminology: addiction, substance use disorder, substance-related disorder, cocaine, methamphetamine, amphetamine, alcohol, nicotine, tobacco, smoking, marijuana, cannabis, heroin, opiates, opioids, and hallucinogens. Results revealed that there are currently several forms of neuromodulation, both invasive and non-invasive, which are being investigated for the treatment of substance use disorder. Preliminary findings have demonstrated the potential of these various neuromodulation techniques in improving substance treatment outcomes by reducing those risk factors (e.g. substance craving) associated with relapse. Specifically, transcranial magnetic stimulation has shown the most promise with several well-designed studies supporting the potential for reducing substance craving. Deep brain stimulation has also shown promise, though lacks well-controlled clinical trials to support its efficacy. Transcranial direct current stimulation has also demonstrated promising results though consistently designed, randomized trials are also needed. There are several other forms of neuromodulation which have not yet been investigated clinically but warrant further investigation given their mechanisms and potential efficacy based on findings from other studied indications. In summary, given promising findings in reducing substance use and craving, neuromodulation may provide a non-pharmacological option as a potential treatment and/or treatment augmentation for substance use disorder. Further research investigating neuromodulation, both alone and in combination with already established substance use disorder treatment (e.g. medication treatment), warrants consideration.

AI snapshot

Written from the paper’s full text.

TL;DR

This review surveys invasive and non-invasive neuromodulation modalities for substance use disorder (SUD), reporting that transcranial magnetic stimulation (TMS) has the strongest preliminary evidence for reducing craving, while deep brain stimulation (DBS) and transcranial direct current stimulation (tDCS) show promise but need better-controlled trials. It argues neuromodulation may be useful as stand-alone or adjunctive SUD treatment, though most evidence remains early-phase and focused on craving rather than actual substance use.

Key findings

  • TMS has shown the most promise, with several well-designed studies supporting reduced substance craving. In the largest cited smoking trial, 115 regular cigarette smokers received 10 daily TMS treatments; cue exposure amplified reductions in cigarette consumption and nicotine dependence. There are over 20 published manuscripts on TMS for smoking, and one rTMS study in opioid use disorder found a single session to the left DLPFC reduced cue-induced craving.
  • DBS case reports describe reduced alcohol, nicotine, and heroin use with nucleus accumbens stimulation. One heroin case abstained during active DBS for 2.5 years and remained drug free for 3.5 years after DBS removal without relapse at 6-year follow-up; in five treatment-resistant alcohol use disorder patients, all reported complete absence of alcohol craving up to 8 years after implantation, with two abstinent for several years and three showing marked reduction. However, DBS lacks well-controlled clinical trials.
  • tDCS findings are inconsistent, but positive studies report reduced cue-induced nicotine craving and smoking, reduced alcohol craving versus sham, reduced cocaine craving after five DLPFC sessions versus sham, and reduced cannabis craving versus sham. The paper notes that 20 or more tDCS sessions may be needed for clinically significant changes.
  • Other modalities: percutaneous nerve field stimulation (PNFS) is FDA approved to reduce opioid withdrawal symptoms; in a single-arm, open-label, retrospective study of 73 patients, mean Clinical Opioid Withdrawal Score fell by 62.7% twenty minutes after initiation, and in 33 patients returning at five days the mean withdrawal score reduction was 97.1%. VNS had no published human addiction trials identified, LIFU had not yet been investigated for SUD, and trigeminal nerve stimulation is approved for ADHD in ages 7–12.

Methods

  • Narrative review using PubMed, PsycINFO, Ovid MEDLINE, Web of Science, and clinicaltrials.gov, with search terms for brain stimulation modalities and addiction; only English-language publications were included in the broader search.
  • A PubMed bibliometric search identified 22,098 brain stimulation entries, 139,236 addiction entries, 188 meeting both criteria, and 106 involving TMS; for Fig. 1 it was limited to human original research, excluding reviews, meta-analyses, and editorials, while the broader review included those publication types and relevant references.
  • No formal meta-analysis or quantitative synthesis is described.

Limitations

  • Stated by the paper: DBS lacks well-controlled clinical trials; tDCS has inconsistent findings and methodological limitations including varying designs, too few sessions, small samples, and insufficient power; PNFS evidence comes from an uncontrolled retrospective study; most SUD neuromodulation research is Phase I with craving as the primary outcome, and craving reduction is necessary but not sufficient for abstinence; literature integrating neuromodulation with psychosocial and pharmacological treatment is lacking; the optimal cortical target is unclear, and many SUD TMS investigations use depression parameters rather than addiction evidence.
  • Evident from the text: the review relies heavily on case reports and small preliminary trials for DBS and several other modalities, and it does not provide a systematic, quantitative synthesis of outcomes.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.jns.2020.117149

Cites

138 of 138 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 121 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    TMS applications to investigate and modulate SUD-related networks have grown exponentially across alcohol, cocaine, methamphetamine, opioid, cannabis, and tobacco use disorders.

    “there has been an exponential growth in the application of TMS to investigate and modulate these networks in populations with SUDs including alcohol, cocaine, methamphetamine, opioid, cannabis, and tobacco use disorder [11,12,25–29].”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [11] Gorelick DA, Zangen A, George MS, Transcranial magnetic stimulation in the treatment of substance addiction, Ann. N. Y. Acad. Sci. 1327 (2014) 79– 93. 25069523 PMC4206564 source

      Not checked in the free run.

    • cites [12] Mishra BR, Praharaj SK, Katshu MZ, Sarkar S, Nizamie SH, Comparison of anticraving efficacy of right and left repetitive transcranial magnetic stimulation in alcohol dependence: a randomized double-blind study, J. Neuropsychiatr. Clin. Neurosci. 27 (1) (2015) e54– e59. 25255169 source

      Not checked in the free run.

    • cites [25] Barr MS, Farzan F, Wing VC, George TP, Fitzgerald PB, Daskalakis ZJ, Repetitive transcranial magnetic stimulation and drug addiction, Int. Rev. Psychiatry 23 (5) (2011) 454– 466. 22200135 source

      Not checked in the free run.

    • cites [26] Hanlon CA, Dowdle LT, Moss H, Canterberry M, George MS, Mobilization of medial and lateral frontal-striatal circuits in cocaine users and controls: an interleaved TMS/BOLD functional connectivity study, Neuropsychopharmacology 41 (13) (2016) 3032– 3041. 27374278 PMC5101551 source

      Not checked in the free run.

    • cites [27] Hanlon CA, Kearney-Ramos T, Dowdle LT,, Developing repetitive transcranial magnetic stimulation (rTMS) as a treatment tool for cocaine use disorder: a series of six translational studies, Curr. Behav. Neurosci. Rep. 4 (4) (2017) 341– 352. 30009124 PMC6039979 source

      Not checked in the free run.

    • cites [28] Li X, Hartwell KJ, Owens M,, Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex reduces nicotine cue craving, Biol. Psychiatry 73 (8) (2013) 714– 720. 23485014 PMC3615051 source

      Not checked in the free run.

    • cites [29] Liu T, Li Y, Shen Y, Liu X, Yuan TF, Gender does not matter: add-on repetitive transcranial magnetic stimulation treatment for female methamphetamine dependents, Prog. Neuro-Psychopharmacol. Biol. Psychiatry 92 (2018) 70– 75. 30605708 source

      Not checked in the free run.

  • Premisecitation

    Reduced inhibitory control and disinhibition are linked to relapse susceptibility.

    “Reduced inhibitory control and disinhibition are also associated with relapse susceptibility [13–17].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [13] Herremans SC, Van Schuerbeek P, De Raedt R,, The impact of accelerated right prefrontal high-frequency repetitive transcranial magnetic stimulation (rTMS) on Cue-reactivity: an fMRI study on craving in recently detoxified alcohol-dependent patients, PLoS One 10 (8) (2015) e0136182. 26295336 PMC4546410 source

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    • cites [14] Kravitz AV, Tomasi D, LeBlanc KH,, Cortico-striatal circuits: novel therapeutic targets for substance use disorders, Brain Res. 1628 (Pt A) (2015) 186– 198. 25863130 PMC9364041 source

      Not checked in the free run.

    • cites [15] Prikryl R, Ustohal L, Kucerova HP,, Repetitive transcranial magnetic stimulation reduces cigarette consumption in schizophrenia patients, Prog. Neuro-Psychopharmacol. Biol. Psychiatry 49 (2014) 30– 35. 24211840 source

      Not checked in the free run.

    • cites [16] Protasio MI, da Silva JP, Arias-Carrion O, Nardi AE, Machado S, Cruz MS, Repetitive transcranial magnetic stimulation to treat substance use disorders and compulsive behavior, CNS Neurol. Disord. Drug Targets 14 (3) (2015) 331– 340. 25801835 source

      Not checked in the free run.

    • cites [17] Feil J, Zangen A, Brain stimulation in the study and treatment of addiction, Neurosci. Biobehav. Rev. 34 (4) (2010) 559– 574. 19914283 source

      Not checked in the free run.

  • Premisecitation

    Chronic drug use, especially chronic alcohol use, causes cortical atrophy.

    “chronic drug use (specifically chronic alcohol use) leads to cortical atrophy [36]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] de la Monte SM, Kril JJ, Human alcohol-related neuropathology, Acta Neuropathol. 127 (1) (2014) 71– 90. 24370929 PMC4532397 source

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  • Premisecitation

    Medication effects are modest in size for smoking cessation.

    “and smoking cessation [7]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Wu L, He Y, Jiang B,, The effect of a very brief smoking-reduction intervention in smokers who have no intention to quit: study protocol for a randomized controlled trial, BMC Public Health 15 (2015) 418. 25944023 PMC4443634 source

      Not checked in the free run.

  • Interpretationreasoning

    Because of promising findings on substance use and craving, neuromodulation may offer a non-pharmacological treatment or augmentation for SUD.

    “given promising findings in reducing substance use and craving, neuromodulation may provide a non-pharmacological option as a potential treatment and/or treatment augmentation for substance use disorder.”
    Quote in the paperSubstantial claim
  • May combine two claims. 44
  • Classified as probably not a substantial claim. 24

  • May combine two claims.

    Findingown data

    Among PubMed entries, 22,098 matched Brain Stimulation criteria and 139,236 matched Addiction criteria; 188 matched both, and 106 of those involved TMS.

    “Of the 22,098 entries that met criteria for Brain Stimulation, and the 139,236 that met criteria for Addiction, there were 188 that met criteria for both (blue bars) and of these, 106 included a form of TMS (red bars).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    TMS made up 78% of publications from 1999 to 2008, while 46% of publications from 2009 to 2019 used non-TMS techniques.

    “TMS accounted for 78% of the publications from 1999 to 2008, whereas 46% of the publications utilized techniques other than TMS from 2009 to 2019.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In 2018, about 20.3 million people in the United States met criteria for a substance use disorder.

    “approximately 20.3 million people had a substance use disorder (SUD) diagnosis in 2018 [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Center for Behavioral Health Statistics and Quality, National SURVEY on Drug Use and Health: Detailed Tables, Rockville MD (2018), p. 2019.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low-frequency continuous rTMS lowers cortical excitability, while high-frequency intermittent rTMS raises it.

    “low frequency, continuous stimulation decreases cortical excitability wherein high frequency, intermittent stimulation leads to an increase in cortical excitability [39,40].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] Chen R, Classen J, Gerloff C,, Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation, Neurology 48 (5) (1997) 1398– 1403. 9153480

      Not checked in the free run.

    • cites [40] Pascual-Leone A, Valls-Sole J, Wassermann EM, Hallett M, Responses to rapidrate transcranial magnetic stimulation of the human motor cortex, Brain 117 (Pt 4) (1994) 847– 858. 7922470

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  • May combine two claims.

    Interpretationnone given

    DBS also appears promising, but well-controlled clinical trials supporting its efficacy are lacking.

    “Deep brain stimulation has also shown promise, though lacks well-controlled clinical trials to support its efficacy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Because the PFC and subcortical limbic and reward structures are richly interconnected, cortical stimulation can indirectly affect those subcortical regions despite limited depth.

    “given the rich interconnectivity between the prefrontal cortex (PFC) and subcortical limbic and reward system structures [32–35], these regions are able to be indirectly impacted by the cortical stimulation, somewhat alleviating the limitation of reduced depth.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [32] Tekin S, Cummings JL, Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update, J. Psychosom. Res. 53 (2) (2002) 647– 654. 12169339 source

      Not checked in the free run.

    • cites [33] Haber SN, Kim KS, Mailly P, Calzavara R, Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning, J. Neurosci. 26 (32) (2006) 8368– 8376. 16899732 PMC6673798 source

      Not checked in the free run.

    • cites [34] Ongur D, Price JL, The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans, Cereb. Cortex 10 (3) (2000) 206– 219. 10731217 source

      Not checked in the free run.

    • cites [35] Leh SE, Ptito A, Chakravarty MM, Strafella AP, Fronto-striatal connections in the human brain: a probabilistic diffusion tractography study, Neurosci. Lett. 419 (2) (2007) 113– 118. 17485168 PMC5114128

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These neuromodulation methods have shown promising early results for reducing substance use and craving, though they are not approved for SUD.

    “While not yet approved for the treatment of SUD, these forms of neuromodulation mentioned above have demonstrated promising preliminary results in reducing substance use and craving.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Many patients never begin extended-release naltrexone because withdrawal symptoms are hard to tolerate, and many who begin stop.

    “many patients never even start the treatment because of difficulty tolerating the withdrawal symptoms and those who start often discontinue [10].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Jarvis BP, Holtyn AF, Subramaniam S,, Extended-release injectable naltrexone for opioid use disorder: a systematic review, Addiction 113 (7) (2018) 1188– 1209. 29396985 PMC5993595

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Deng et al. 2013 computational models found figure-of-8 coils affected about 10 cm2 of cortical surface, circular coils about 50 cm2, and H-coils about 100 cm2.

    “typical figure-of-8 coil designs affected approximately 10 cm2 of cortical surface, circular coils affected approximately 50cm2, and H-coil designs affected approximately 100 cm2.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Deng ZD, Lisanby SH, Peterchev AV, Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs, Brain Stimul. 6 (1) (2013) 1– 13. 22483681 PMC3568257

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In 2018, just 3.7 million people out of over 20 million with SUD obtained any SUD treatment.

    “of the more than 20 million individuals with SUD in 2018, only 3.7 million people received any form of SUD treatment [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Center for Behavioral Health Statistics and Quality, National SURVEY on Drug Use and Health: Detailed Tables, Rockville MD (2018), p. 2019.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    For 2018, about 9.5 million American adults experienced both mental illness and SUD within the previous year.

    “an estimated 9.5 million adults (approximately 4% of all adults) had both mental illness and SUD in the past year”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Center for Behavioral Health Statistics and Quality, National SURVEY on Drug Use and Health: Detailed Tables, Rockville MD (2018), p. 2019.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    For 2018, 3.2 million adults had serious mental illness together with SUD.

    “3.2 million adults had co-occurring serious mental illness and SUD [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Center for Behavioral Health Statistics and Quality, National SURVEY on Drug Use and Health: Detailed Tables, Rockville MD (2018), p. 2019.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a randomized multicenter depression trial, intermittent TBS was non-inferior to traditional TMS for outcomes, side effects, safety, and tolerability.

    “In a randomized, multicenter, clinical trial in patients with depression, intermittent TBS was found to be non-inferior to traditional TMS with regard to outcomes, side-effects, safety, and tolerability [43].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Blumberger DM, Vila-Rodriguez F, Thorpe KE,, Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial, Lancet 391 (10131) (2018) 1683– 1692. 29726344 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    tDCS has shown promising results, but consistently designed randomized trials are still needed.

    “Transcranial direct current stimulation has also demonstrated promising results though consistently designed, randomized trials are also needed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    This suggests that higher stimulation intensity or a bent coil may better reach the cortex in these individuals.

    “which suggests that a higher stimulation intensity or a bent coil may be more likely to reach the cortex of these individuals.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    TMS appears most promising, with several well-designed studies supporting its potential to reduce substance craving.

    “transcranial magnetic stimulation has shown the most promise with several well-designed studies supporting the potential for reducing substance craving.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The NAc connects directly and indirectly with the dorsal striatum, amygdala, and hippocampus, regions tied to emotion, self-regulation, disinhibition, insight, craving, and habit formation.

    “the NAc also maintains direct and indirect involvement with several brain regions, such as the dorsal striatum, amygdala, and hippocampus, areas which are associated with emotions, self-regulation, disinhibition, insight, craving, and habit forming [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Koob GF, Volkow ND, Neurobiology of addiction: a neurocircuitry analysis, Lancet Psychiatry 3 (8) (2016) 760– 773. 27475769 PMC6135092 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most flat figure-of-eight and circular coils reached depths of 1 to 2 cm, while H-coils reached 2 to 3 cm.

    “Most flat figure-of-eight and circular coil designs had penetration depths from 1 to 2 cm2, whereas the H-coil designs had consistently higher depths of 2–3 cm.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Deng ZD, Lisanby SH, Peterchev AV, Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs, Brain Stimul. 6 (1) (2013) 1– 13. 22483681 PMC3568257

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The prefrontal cortical network, including DLPFC and OFC, supports inhibitory control, which is often impaired in SUD patients.

    “these regions include the prefrontal cortical network including the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex [11,12] which have important functions in inhibitory control, a neurobehavioral output often impaired in patients with SUDs.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [11] Gorelick DA, Zangen A, George MS, Transcranial magnetic stimulation in the treatment of substance addiction, Ann. N. Y. Acad. Sci. 1327 (2014) 79– 93. 25069523 PMC4206564 source

      Not checked in the free run.

    • cites [12] Mishra BR, Praharaj SK, Katshu MZ, Sarkar S, Nizamie SH, Comparison of anticraving efficacy of right and left repetitive transcranial magnetic stimulation in alcohol dependence: a randomized double-blind study, J. Neuropsychiatr. Clin. Neurosci. 27 (1) (2015) e54– e59. 25255169 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Extended-release naltrexone and buprenorphine have high relapse rates, 65% and 57% respectively.

    “extended release naltrexone and buprenorphine have unacceptably high relapse rates (65% vs. 57% respectively) [9].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Lee JD, Nunes EV Jr., Novo P,, Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial, Lancet 391 (10118) (2018) 309– 318. 29150198 PMC5806119 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Several other neuromodulation forms have not been studied clinically but deserve further investigation because of their mechanisms and potential efficacy from other indications.

    “There are several other forms of neuromodulation which have not yet been investigated clinically but warrant further investigation given their mechanisms and potential efficacy based on findings from other studied indications.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The NAc is regarded as the reward circuitry's center and is strongly implicated in substance use and craving.

    “The primary subcortical brain target is the nucleus accumbens (NAc) which is considered the center of the reward circuitry and heavily implicated in substance use and craving [18–22].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [18] Di Chiara G, Nucleus accumbens shell and core dopamine: differential role in behavior and addiction, Behav. Brain Res. 137 (1–2) (2002) 75– 114. 12445717 source

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    • cites [19] Koob GF, Volkow ND, Neurobiology of addiction: a neurocircuitry analysis, Lancet Psychiatry 3 (8) (2016) 760– 773. 27475769 PMC6135092 source

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    • cites [20] Volkow ND, Koob GF, McLellan AT, Neurobiologic advances from the brain disease model of addiction, N. Engl. J. Med. 374 (4) (2016) 363– 371. 26816013 PMC6135257 source

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    • cites [21] Volkow ND, Morales M, The brain on drugs: from reward to addiction, Cell 162 (4) (2015) 712– 725. 26276628 source

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    • cites [22] Volkow ND, Wang GJ, Fowler JS, Tomasi D, Addiction circuitry in the human brain, Annu. Rev. Pharmacol. Toxicol. 52 (2012) 321– 336. 21961707 PMC3477468 source

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  • May combine two claims.

    Premisecitation

    In a study of five participants with treatment-resistant alcohol use disorder who received DBS of the NAc, all reported a complete absence of craving for alcohol up to 8 years following DBS implantation; two patients remained abstinent for several years, and three showed a marked reduction of alcohol consumption.

    “In a study of five participants with treatment-resistant alcohol use disorder who received DBS of the NAc, all reported a complete absence of craving for alcohol up to 8 years following DBS implantation; two patients remained abstinent for several years, and three showed a marked reduction of alcohol consumption [90].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [90] Muller UJ, Sturm V, Voges J,, Nucleus Accumbens deep brain stimulation for alcohol addiction – safety and clinical long-term results of a pilot trial, Pharmacopsychiatry 49 (4) (2016) 170– 173. 27145161 source

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    Premisecitation

    In patients refractory to traditional pain treatment, HIFU pain relief is relatively rapid, within a day, and can persist one year after treatment.

    “the effects of HIFU treatment in pain reduction are relative rapid (within a day of sonication) in patients refractory to treatment with more traditional methods, exhibiting benefit one year after treatment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [62] Brown MR, Farquhar-Smith P, Williams JE, ter Haar G, deSouza NM. The use of high-intensity focused ultrasound as a novel treatment for painful conditions-a description and narrative review of the literature, Br. J. Anaesth. 115 (4) (2015) 520– 530. 26385662

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several clinical investigations have explored DBS for neurobehavioral disorders including OCD, depression, Tourette's disease, eating disorders, traumatic brain injury, and Alzheimer's disease.

    “Several clinical investigations have explored the utility of DBS to treat a range of neurobehavioral disorders including OCD, depression, Tourette’s disease, eating disorders, traumatic brain injury, and Alzheimer’s disease [71–86].”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [71] Alonso P, Cuadras D, Gabriels L,, Deep brain stimulation for obsessive-compulsive disorder: a meta-analysis of treatment outcome and predictors of response, PLoS One 10 (7) (2015) e0133591. 26208305 PMC4514753 source

      Not checked in the free run.

    • cites [72] de Haan S, Rietveld E, Stokhof M, Denys D, Effects of deep brain stimulation on the lived experience of obsessive-compulsive disorder patients: in-depth interviews with 18 patients, PLoS One 10 (8) (2015) e0135524. 26312488 PMC4552296

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    • cites [73] Denys D, Mantione M, Figee M,, Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder, Arch. Gen. Psychiatry 67 (10) (2010) 1061– 1068. 20921122 source

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    • cites [74] Dougherty DD, Rezai AR, Carpenter LL,, A randomized sham-controlled trial of deep brain stimulation of the ventral capsule/ventral striatum for chronic treatment-resistant depression, Biol. Psychiatry 78 (4) (2015) 240– 248. 25726497 source

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    • cites [75] Greenberg BD, Gabriels LA, Malone DA Jr., Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience, Mol. Psychiatry 15 (1) (2010) 64– 79. 18490925 PMC3790898 source

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    • cites [76] Greenberg BD, Malone DA, Friehs GM,, Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder, Neuropsychopharmacology 31 (11) (2006) 2384– 2393. 16855529

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    • cites [77] Hamani C, Andrade D, Hodaie M, Wennberg R, Lozano A, Deep brain stimulation for the treatment of epilepsy, Int. J. Neural Syst. 19 (3) (2009) 213– 226. 19575509

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    • cites [78] Houeto JL, Karachi C, Mallet L,, Tourette’s syndrome and deep brain stimulation, J. Neurol. Neurosurg. Psychiatry 76 (7) (2005) 992– 995. 15965209 PMC1739716

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    • cites [79] Laxton AW, Tang-Wai DF, McAndrews MP,, A phase I trial of deep brain stimulation of memory circuits in Alzheimer’s disease, Ann. Neurol. 68 (4) (2010) 521– 534. 20687206

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    • cites [80] Lipsman N, Woodside B, Lozano AM, Evaluating the potential of deep brain stimulation for treatment-resistant anorexia nervosa, Handb. Clin. Neurol. 116 (2013) 271– 276. 24112901

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    DBS for pain reduction has demonstrated favorable results when other methods such as medications have not been successful.

    “DBS for pain reduction has demonstrated favorable results when other methods, such as medications have not been successful.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [87] Falowski SM, Deep brain stimulation for chronic pain, Curr. Pain Headache Rep. 19 (7) (2015) 27. 26049773

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HIFU is FDA approved for Parkinson's disease tremor and essential tremor.

    “is FDA approved for the treatment of tremor associated with Parkinson’s disease [59] and essential tremor [60,61].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [59] Sperling SA, Shah BB, Barrett MJ,, Focused ultrasound thalamotomy in Parkinson disease: nonmotor outcomes and quality of life, Neurology 91 (14) (2018) e1275– e1284. 30158160

      Not checked in the free run.

    • cites [60] Lipsman N, Schwartz ML, Huang Y,, MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study, Lancet Neurol. 12 (5) (2013) 462– 468. 23523144 source

      Not checked in the free run.

    • cites [61] Martin E, Jeanmonod D, Morel A, Zadicario E, Werner B, High-intensity focused ultrasound for noninvasive functional neurosurgery, Ann. Neurol. 66 (6) (2009) 858– 861. 20033983

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FUS is a non-invasive technique that can precisely target subcortical brain structures and modulate neural circuitry.

    “Transcranial focused ultrasound (FUS) is a non-invasive technique which has the capability to precisely target subcortical brain structures and modulate neural circuitry [56,57].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [56] di Biase L, Falato E, Di Lazzaro V, Transcranial focused ultrasound (tFUS) and transcranial unfocused ultrasound (tUS) neuromodulation: from theoretical principles to stimulation practices, Front. Neurol. 10 (2019) 549. 31244747 PMC6579808

      Not checked in the free run.

    • cites [57] Bowary P, Greenberg BD, Noninvasive focused ultrasound for neuromodulation: a review, Psychiatr Clin. North Am. 41 (3) (2018) 505– 514. 30098661

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    HIFU is emerging as a viable treatment for chronic pain.

    “HIFU is also emerging as a viable treatment option for chronic pain [62]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [62] Brown MR, Farquhar-Smith P, Williams JE, ter Haar G, deSouza NM. The use of high-intensity focused ultrasound as a novel treatment for painful conditions-a description and narrative review of the literature, Br. J. Anaesth. 115 (4) (2015) 520– 530. 26385662

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Anodal tDCS involves depolarization of neurons, increasing cortical excitability; cathodal tDCS involves hyperpolarization, decreasing cortical excitability.

    “Anodal tDCS involves the depolarization of neurons, subsequently increasing cortical excitability, while cathodal tDCS involves the hyperpolarization of neurons, subsequently decreasing cortical excitability [97].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Nitsche MA, Paulus W, Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans, Neurology 57 (10) (2001) 1899– 1901. 11723286

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a prospective double-blind sham-controlled study, 115 regular cigarette smokers were randomized to 10 daily TMS treatments, with half shown visual smoking cues before each session.

    “In this prospective, double-blind, sham-controlled study, 115 regular cigarette smokers were randomized to receive 10 daily treatments of TMS. Immediately before each session, half of the participants were presented with visual smoking cues.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Dinur-Klein L, Dannon P, Hadar A,, Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: a prospective, randomized controlled trial, Biol. Psychiatry 76 (9) (2014) 742– 749. 25038985 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    LIFU has the potential to provide results of greater magnitude than other forms of neuromodulation given its exceptional spatial resolution and ability to target deeper subcortical structures such as the NAc.

    “LIFU has the potential to provide results of greater magnitude than other forms of neuromodulation given the exceptional spatial resolution and ability to target deeper, subcortical structures such as the NAc.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: LIFU as a potential treatment for SUD has not yet been investigated.

  • May combine two claims.

    Premisecitation

    LIFU creates reversible functional lesions with no pathological changes on histological examination, unlike HIFU's permanent lesions.

    “LIFU is considered an emerging form of non-invasive neuromodulation as it creates reversible functional lesions that produce no pathological changes on histological examination [58].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] Darrow DP, Focused ultrasound for neuromodulation, Neurotherapeutics 16 (1) (2019) 88– 99. 30488340 PMC6361056

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent study found that in healthy controls DLPFC stimulation reciprocally attenuated Brodmann 10 in the MPFC, but this did not occur in cocaine users.

    “within healthy controls, there was a reciprocal relationship between DLPFC stimulation and subsequent attenuation of Brodmann 10 in the MPFC, but this was not present in cocaine users [49].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [49] Hanlon CA, Dowdle LT, Moss H, Canterberry M, George MS, Mobilization of medial and lateral frontal-striatal circuits in cocaine users and controls: an interleaved TMS/BOLD functional connectivity study, Neuropsychopharmacology 41 (2016) 3032– 3041. 27374278 PMC5101551 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The best cortical target in substance users remains unclear, and many current SUD studies use depression parameters rather than addiction evidence.

    “the optimal cortical location to target in substance users is unclear and many of the current investigations in SUD are based on the parameters used for depression rather than evidence from addiction literature.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    LIFU has exceptional spatial resolution and can target deeper subcortical structures.

    “LIFU is unique among neuromodulatory methods in that it not only has exceptional spatial resolution [64–66] but also has the capability of targeting deeper, subcortical structures [67].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [64] Mehic E, Xu JM, Caler CJ, Coulson NK, Moritz CT, Mourad PD, Increased anatomical specificity of neuromodulation via modulated focused ultrasound, PLoS One 9 (2) (2014) e86939. 24504255 PMC3913583

      Not checked in the free run.

    • cites [65] Robertson JL, Cox BT, Jaros J, Treeby BE, Accurate simulation of transcranial ultrasound propagation for ultrasonic neuromodulation and stimulation, J. Acoust. Soc. Am. 141 (3) (2017) 1726. 28372121

      Not checked in the free run.

    • cites [66] Yoo SS, Bystritsky A, Lee JH,, Focused ultrasound modulates region-specific brain activity, Neuroimage 56 (3) (2011) 1267– 1275. 21354315 PMC3342684

      Not checked in the free run.

    • cites [67] Rezayat E, Toostani IG, A review on brain stimulation using low intensity focused ultrasound, Basic Clin. Neurosci. 7 (3) (2016) 187– 194. 27563411 PMC4981830

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    tDCS is not FDA approved for any indications, though trials have demonstrated potential efficacy in the treatment of depression, anxiety, and other psychiatric disorders.

    “Currently, tDCS is not FDA approved for any indications though trials have demonstrated potential efficacy in the treatment of depression [98], anxiety [99], and other psychiatric disorders [100].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [98] Razza LB, Palumbo P, Moffa AH,, A systematic review and meta-analysis on the effects of transcranial direct current stimulation in depressive episodes, Depress Anxiety (2020). 32101631

      Not checked in the free run.

    • cites [99] Stein DJ, Fernandes Medeiros L, Caumo W, Torres IL, Transcranial direct current stimulation in patients with anxiety: current perspectives, Neuropsychiatr. Dis. Treat. 16 (2020) 161– 169. 32021208 PMC6969693

      Not checked in the free run.

    • cites [100] Kekic M, Boysen E, Campbell IC, Schmidt U, A systematic review of the clinical efficacy of transcranial direct current stimulation (tDCS) in psychiatric disorders, J. Psychiatr. Res. 74 (2016) 70– 86. 26765514

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In that trial, cigarette consumption and nicotine dependence decreased, with the largest effects in those exposed to smoking cues.

    “There was reduced cigarette consumption and nicotine dependence, and the effects were greatest in the individuals that were exposed to smoking cues [46].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Dinur-Klein L, Dannon P, Hadar A,, Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: a prospective, randomized controlled trial, Biol. Psychiatry 76 (9) (2014) 742– 749. 25038985 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Implementing TMS for the treatment of SUD will also reduce co-occurring symptoms which interfere with successful treatment.

    “Given that TMS is FDA approved for the treatment of depression and has also been utilized to treat anxiety, it is certainly plausible that implementing this form of neuromodulation for the treatment of SUD will also reduce these co-occurring symptoms which interfere with successful treatment.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In a clinical trial, ADHD-RS total scores showed significant group-by-time interactions.

    “In a clinical trial, ADHD-RS total scores showed significant group-by-time interactions.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] McGough JJ, Sturm A, Cowen J,, Double-blind, sham-controlled, pilot study of trigeminal nerve stimulation for attention-deficit/hyperactivity disorder, J. Am. Acad. Child Adolesc. Psychiatry 58 (4) (2019) 403– 411 (e403). PMC6481187 30768393 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    LIFU has the potential to overcome the limitations of non-invasive techniques by utilizing a non-invasive approach while having the capability to precisely target relatively smaller, subcortical brain regions.

    “While not yet investigated for SUD, LIFU has the potential to overcome these limitations above by utilizing a preferred non-invasive approach though having the capability to precisely target relatively smaller, subcortical brain regions.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: LIFU as a potential treatment for SUD has not yet been investigated.

  • May combine two claims.

    Interpretationnone given

    Neuromodulation alone has demonstrated positive effects in reducing substance use and those risk factors associated with relapse.

    “While neuromodulation alone has demonstrated positive effects in reducing substance use and those risk factors associated with relapse, perhaps the best approach would be to evaluate the effectiveness of neuromodulation as an adjunctive treatment to already established behavioral and/or pharmacological treatments for SUD (rather than as a stand-alone treatment).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Anodal tDCS targeting the left DLPFC reduced cue-induced alcohol craving and emotional symptoms (e.g., anxiety, depression) compared to sham; however, this form of treatment was associated with a trend toward greater relapse in treatment seeking individuals.

    “Anodal tDCS targeting the left DLPFC reduced cue-induced alcohol craving and emotional symptoms (e.g. anxiety, depression) when compared to sham; however, this form of treatment was associated with a trend toward greater relapse in treatment seeking individuals [109].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [109] da Silva MC, Conti CL, Klauss J,, Behavioral effects of transcranial direct current stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence, J. Physiol. Paris 107 (6) (2013) 493– 502. 23891741 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Studies of nicotine/tobacco have demonstrated that neuromodulation (e.g., TMS, tDCS) can reduce both craving as well as smoking behavior and/or tobacco use.

    “The exception to this includes studies of nicotine/tobacco which have demonstrated that neuromodulation (e.g. TMS, tDCS) can reduce both craving as well as smoking behavior and/or tobacco use [139].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [139] Rachid F, Neurostimulation techniques in the treatment of nicotine dependence: a review, Am. J. Addict. 25 (6) (2016) 436– 451. 27442267 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    Using neuromodulation to improve the altered reward circuitry in those with SUD will make those individuals more likely to comply and engage with other forms of SUD treatment, thus resulting in a higher probability of remaining abstinent.

    “For example, by using neuromodulation to improve the altered reward circuitry in those with SUD, those individuals will then be more likely to comply and engage in with other forms of SUD treatment thus resulting in a higher probability of remaining abstinent.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Reduction of craving is necessary but not sufficient for achieving and maintaining abstinence from an addictive substance or behavior.

    “That being said, while findings have suggested that various forms of neuromodulation can reduce or suppress craving, prior literature has stated that the reduction of craving is necessary but not sufficient for achieving and maintaining abstinence from an addictive substance or behavior [138].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [138] Bari A, DiCesare J, Babayan D, Runcie M, Sparks H, Wilson B, Neuromodulation for substance addiction in human subjects: a review, Neurosci. Biobehav. Rev. 95 (2018) 33– 43. 30268433 PMC7405948

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    CGI-Improvement scores favored active treatment in the TNS trial.

    “CGI-Improvement scores also favored active treatment [127].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] McGough JJ, Sturm A, Cowen J,, Double-blind, sham-controlled, pilot study of trigeminal nerve stimulation for attention-deficit/hyperactivity disorder, J. Am. Acad. Child Adolesc. Psychiatry 58 (4) (2019) 403– 411 (e403). PMC6481187 30768393 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    Treating these symptoms in parallel may lead to improved treatment adherence and engagement and better patient experiences overall, subsequently leading to improved outcomes (sustained abstinence).

    “In other words, treating these symptoms in parallel may lead to improved treatment adherence and engagement and better patient experiences overall, subsequently leading to improved outcomes (sustained abstinence).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    The PNFS trial was not controlled and was conducted retrospectively.

    “While these results are promising, this trial was not controlled and conducted retrospectively, therefore, prospective and controlled clinical trials should be conducted to establish efficacy.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [125] Miranda A, Taca A, Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment, Am. J. Drug Alcohol Abuse 44 (1) (2018) 56– 63. 28301217

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    That individual remained entirely abstinent from all substances and was fully engaged in his comprehensive SUD treatment for approximately one month following the final TMS session, a considerable improvement as he had previously only been able to sustain abstinence for no longer than a few days prior to receiving the TMS treatment.

    “This individual also remained entirely abstinent from all substances and was fully engaged in his comprehensive SUD treatment for approximately one month following the final TMS session, a considerable improvement as he had previously only been to sustain abstinence for no longer than a few days prior to receiving the TMS treatment [141].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [141] Mahoney JJ, Marshalek PJ, Rezai AR, Lander LR, Berry JH, Haut MW, A case report illustrating the effects of repetitive transcranial magnetic stimulation on cue-induced craving in an individual with opioid and cocaine use disorder, Exp. Clin. Psychopharmacol. 28 (1) (2020) 1– 5. 31647279 PMC7037539

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    TNS has recently been approved for the treatment of attention deficit and hyperactivity disorder (ADHD).

    “Trigeminal Nerve Stimulation (TNS) has recently been approved for the treatment of attention deficit and hyperactivity disorder (ADHD).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [126] Food and Drug Administration, FDA Permits Marketing of First Medical Device for Treatment of ADHD, Retrieved from, 2019 https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-first-medical-device-treatment-adhd.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Both invasive and non-invasive methods of neuromodulation have shown promise in the treatment of psychiatric disorders including SUD.

    “Both invasive and non-invasive methods of neuromodulation have shown promise in the treatment of psychiatric disorders including SUD.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Laser irradiation to auricular acupoints of patients with alcohol use disorder reduced depression and symptoms accompanying alcohol withdrawal.

    “While the literature related to PDM for SUD is limited, laser irradiation to auricular acupoints of patients with alcohol use disorder reduced depression and symptoms accompanying alcohol withdrawal [135].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [135] Zalewska-Kaszubska J, Obzejta D, Use of low-energy laser as adjunct treatment of alcohol addiction, Lasers Med. Sci. 19 (2) (2004) 100– 104. 15674998

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Five days following treatment, 33 patients returned to clinic and the mean withdrawal score reduction was 97.1%.

    “Five days following treatment, 33 patients returned to clinic and the mean withdrawal score reduction was 97.1% [125].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [125] Miranda A, Taca A, Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment, Am. J. Drug Alcohol Abuse 44 (1) (2018) 56– 63. 28301217

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Anodal tDCS to both the right and left DLPFC has been shown to reduce cue-induced nicotine craving and smoking behavior.

    “Anodal tDCS to both the right and left DLPFC has been shown to reduce cue-induced nicotine craving and smoking behavior [106,107].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [106] Fregni F, Liguori P, Fecteau S, Nitsche MA, Pascual-Leone A, Boggio PS, Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study, J. Clin. Psychiatry 69 (1) (2008) 32– 40. 18312035

      Not checked in the free run.

    • cites [107] Boggio PS, Liguori P, Sultani N, Rezende L, Fecteau S, Fregni F, Cumulative priming effects of cortical stimulation on smoking cue-induced craving, Neurosci. Lett. 463 (1) (2009) 82– 86. 19619607

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    VNS reduces cocaine seeking and alters plasticity in the extinction network in rats.

    “VNS inhibits heroin-seeking behavior induced by heroin priming or heroin-associated cues in rats [119] and also reduces cocaine seeking and alters plasticity in the extinction network in rats [120].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [120] Childs JE, DeLeon J, Nickel E, Kroener S, Vagus nerve stimulation reduces cocaine seeking and alters plasticity in the extinction network, Learn. Mem. 24 (1) (2017) 35– 42. 27980074 PMC5159656

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Neuromodulation may be effective in extinguishing the learned response to the reinforcing effects of substances, related cues, or other triggers.

    “One of the primary factors contributing to relapse is substance craving [136,137] and, mechanistically, one conceptualization is that neuromodulation may be effective in extinguishing the learned response to the reinforcing effects of substances, related cues, or other triggers.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Brain photobiomodulation (PBM) therapy uses red to near-infrared light and is an innovative treatment for a wide range of neurological and psychological conditions including depression and anxiety.

    “For example, brain photobiomodulation (PBM) therapy, which uses red to near-infrared light, is an innovative treatment for a wide range of neurological and psychological conditions including depression and anxiety [131,132] and there is also preclinical evidence of improvement in cognitive decline [133,134].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [131] Schiffer F, Johnston AL, Ravichandran C,, Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety, Behav. Brain Funct. 5 (2009) 46. 19995444 PMC2796659

      Not checked in the free run.

    • cites [132] Salehpour F, Rasta SH, The potential of transcranial photobiomodulation therapy for treatment of major depressive disorder, Rev. Neurosci. 28 (4) (2017) 441– 453. 28231069

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    While neuromodulation has demonstrated some promising results thus far for the treatment of SUD, more extensive clinical data, subsequent regulatory approvals, and more favorable medical coverage policies will be needed in order to successfully implement this form of treatment.

    “While neuromodulation has demonstrated some promising results thusfar for the treatment of SUD, more extensive clinical data, subsequent regulatory approvals, and more favorable medical coverage policies will be needed in order to successfully implement this form of treatment to overcome the current substance use crisis our nation is facing.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: There is a high prevalence of individuals diagnosed with SUD and an elevated rate of attrition and relapse following treatment initiation.

  • May combine two claims.

    Premisecitation

    A separate case report: an individual with treatment refractory benzodiazepine and opioid use disorder who received DBS of the nucleus accumbens/ventral capsule for polysubstance use disorder demonstrated complete abstinence, significant decreases in craving, and remained fully engaged in comprehensive SUD treatment at 12 and 24 week outpatient assessments.

    “In a separate case report involving DBS of the nucleus accumbens/ventral capsule for polysubstance use disorder, an individual with treatment refractory benzodiazepine and opioid use disorder demonstrated complete abstinence, significant decreases in craving, and remained fully engaged in comprehensive SUD treatment at 12 and 24 week outpatient assessments [142].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [142] Mahoney JJ, Haut M, Hodder S, Zheng W, Lander L, Berry J, Brandmeir N, Ranjan M, Finomore V, Wang G, Tomasi D, Shokri-Kojori E, Rezai A, Deep Brain Stimulation of the Nucleus Accumbens/Ventral Capsule for Co-Occurring Opioid and Benzodiazepine Use Disorder, Oral Presentation at the College on Problems of Drug Dependence Virtual Meeting, June 2020.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisenone given

    Currently, there are several forms of neuromodulation, both invasive and non-invasive, which are being investigated for the treatment of SUD.

    “Currently, there are several forms of neuromodulation, both invasive and non-invasive, which are being investigated for the treatment of SUD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Neuromodulation warrants consideration as a potential treatment given promising findings in reducing substance use and craving in individuals with SUD.

    “Neuromodulation warrants consideration as a potential treatment given promising findings in reducing substance use and craving in individuals with SUD.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: There is a high prevalence of individuals diagnosed with SUD and an elevated rate of attrition and relapse following treatment initiation.
62 of 62

  • The paper relies on this without support.

    Medication treatments for SUD are lacking except for nicotine/tobacco, alcohol, and opioids.

    “Another factor impacting successful treatment is the lack of medication treatments for SUDs, other than medication for nicotine/tobacco, alcohol and opioids.”

  • The paper relies on this without support.

    The DLPFC and surrounding network are associated with substance craving.

    “Furthermore, the DLPFC and surrounding network are also associated with substance craving, a major clinical feature of SUD associated with poor treatment outcomes and relapse.”

  • The paper relies on this without support.

    Neuromodulation has been used therapeutically for neurological and psychiatric disorders.

    “One such approach involves neuromodulation which has been used therapeutically for neurological and psychiatric disorders and has also been used for exploratory purposes in researching the neurocircuitry of the brain.”

  • The paper relies on this without support.

    TMS has demonstrated benefit in reducing symptoms of co-occurring psychiatric disorders such as depression, which may worsen SUD.

    “some forms of neuromodulation, such as TMS, have demonstrated benefit in reducing symptoms of co-occurring psychiatric disorders/symptoms (e.g. depression) which may be further perpetuating and/or exacerbating an individual’s SUD.”

  • The paper relies on this without support.

    LIFU as a potential treatment for SUD has not yet been investigated.

    “While, to the best of our knowledge, LIFU as a potential treatment for SUD has not yet been investigated, this form of neuromodulation warrants consideration.”

  • The paper relies on this without support.

    DBS has not been investigated extensively in addiction.

    “DBS has not been investigated extensively in addiction, though there have been reports of the potential utility of this form of treatment.”

  • The paper relies on this without support.

    No human clinical trials involving VNS for the treatment of addiction have been published or listed on Clinicaltrials.gov.

    “To the best of our knowledge, no human clinical trials involving VNS for the treatment of addiction have been published to date nor listed on the clinical trials listing site Clinicaltrials.gov.”

  • The paper relies on this without support.

    TNS has not yet been investigated for the treatment of SUD.

    “While not yet investigated for the treatment of SUD, the non-invasive TNS warrants consideration.”

  • The authors state this as an assumption.

    If one assumes the same degree of treatment resistance to SUD treatment that is found across other psychiatric conditions, it is equally likely that several failed medication trials will have similar diminishing returns.

    “Additionally, if one assumes the same degree of treatment resistance to SUD treatment that is found across other psychiatric conditions, it is equally likely that several failed medication trials will have similar diminishing returns.”

  • The paper relies on this without support.

    There is a high prevalence of individuals diagnosed with SUD and an elevated rate of attrition and relapse following treatment initiation.

    “Given the high prevalence of individuals diagnosed with SUD, along with the elevated rate of attrition and relapse following treatment initiation, investigating novel approaches and new modalities to treat and/or augment SUD treatment is of vital importance.”
10 of 10

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Non-invasive neuromodulation techniques include transcranial magnetic stimulation, transcranial direct current stimulation, and low-intensity focused ultrasound targeting the dorsolateral prefrontal cortex and the insula.

    “Non- invasive techniques include transcranial magnetic stimu lation, transcranial direct current stimulation, and low- intensity focused ultrasound 214 targeting the dorsolateral prefrontal cortex and the insula 73 .”

    From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [214]

    The Introduction identifies TMS and tDCS as non-invasive techniques and names the dorsolateral prefrontal cortex as a target; the Discussion also identifies LIFU as non-invasive. The passages on focused ultrasound discuss deeper targets but do not identify the insula as a target for these techniques. The supplied passages have section labels but no page numbers. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Hanlon, 2016, Mobilization of medial and lateral frontal-striatal circuits in cocaine users and controls: an interleaved TMS/BOLD functional connectivity study, Neuropsychopharmacology, 41, 3032, 10.1038/npp.2016.114 · DOI · Paper page

Cited by

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Related

Authors
Mahoney, J. J., Hanlon, C. A., Marshalek, P. J., Rezai, A. R., & Krinke, L.
Affiliations
  • West Virginia University (US)
  • Wake Forest University Health Sciences (US)
Corresponding author
Mahoney, James J.
ORCID
Venue
Journal of the Neurological Sciences
Publisher
Elsevier BV
Published
2020-11
Volume
418
Pages
117149
ISSN
0022-510X (ISSN-L)
DOI
10.1016/j.jns.2020.117149
PMC
PMC7702181
OpenAlex
W3091232918
Semantic Scholar
ffd6a7d7742e532c45c6b8f43c33c54e1835b691
Cited by
121
References
138
Citations by year
2026: 14 · 2025: 24 · 2024: 29 · 2023: 27 · 2022: 23 · 2021: 4
FWCI
1.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the Neurological Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (U54GM104942)
  • National Institute of General Medical Sciences
  • National Institute on Drug Abuse (R01DA044471, R21DA044503)
Topics
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
substance use disorders, neuromodulation, transcranial magnetic stimulation, deep brain stimulation, transcranial direct current stimulation, theta burst stimulation, vagus nerve stimulation, trigeminal nerve stimulation, low-intensity focused ultrasound, drug craving, relapse, addiction treatment, non-pharmacological treatment, augmentation therapy
MeSH terms
Humans, Substance-Related Disorders, Deep Brain Stimulation, Transcranial Magnetic Stimulation, Vagus Nerve Stimulation, Transcranial Direct Current Stimulation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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