(47) Neuromodulation in Transitional Age Youth Substance Use Disorders: A Narrative Review

Background & Introduction: Substance use disorders (SUDs) among youth represent a significant public health crisis, often resulting in severe long-term consequences that impact physical and mental health, social functioning, and economic stability. Traditional treatment approaches often demonstrate limited efficacy in this vulnerable population, underscoring the urgent need for innovative interventions. Non-invasive neuromodulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), offer promising avenues for targeting the neurobiological underpinnings of addiction. Youth may particularly benefit from these approaches due to their heightened neuroplasticity, potentially amplifying the therapeutic effects of neuromodulation compared to adults. While neuromodulation in adults has yielded mixed results with limited regulatory approvals, the potential in younger populations remains largely unexplored. This narrative review examines the current evidence for the use of TMS and tDCS in treating of SUDs and associated comorbidities in transitional age youth. By synthesizing the existing research, we aim to assess the potential of these non-invasive brain stimulation methods to improve outcomes for young people struggling with substance use, leveraging their enhanced neuroplasticity to enter recovery.

Methods: Four comprehensive searches of Pubmed, Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; Ovid APA PsycINFO; Web of Science Core Collection via Clarivate Analytics; and Scopus via Elsevier were conducted. The first search was completed in February 2022 and updated in December 2022, March 2024, and January 2025.

“Transitional age youth” was operationally defined as study populations under the age of 27, and our inclusion criteria required that all participants of included studies be aged 27 or younger. Clinical trials and case studies utilizing rTMS, tDCS, transcranial alternating current stimulation (tACS), and focused ultrasound with the intention of treating one or more SUDs or directly associated comorbid symptoms were considered.

Results: Our comprehensive literature search across multiple databases yielded 2620 records. After applying our inclusion/exclusion criteria (participants aged 27 or younger, studies utilizing rTMS, tDCS, or transcranial alternating current stimulation (tACS) for SUDs or related comorbidities), ten studies were included in the final analysis. Of the included studies, six investigated the use of rTMS, and four explored tDCS. Some studies had primary substances of focus while the others included multiple substances.

rTMS findings: The rTMS studies included four sham-controlled trials and two case studies. High frequency rTMS (HF-rTMS) targeting the right (rDLPFC) or the left (DLPFC) dorsolateral prefrontal cortices produced immediate changes in craving after a single treatment and sustained changes after multiple treatments. One trial found that HF-rTMS over the rDLPFC outperformed HF-rTMS over the lDLPFC in immediate craving reduction. A single Low Frequency rTMS (LF-rTMS) treatment targeting the lDLPFC did not seem to influence cue-induced craving in a small trial, but five sessions over the rDLPFC in produced immediate craving reduction that was sustained after three months and improvement in mood symptoms in a reported case study. Both HF-rTMS over the lDLPFC and LF-rTMS over the rDLPFC were linked to abstinence of at least one month’s duration in case studies. Continuous theta burst stimulation (cTBS) over either the rDLPFC or lDLPFC were both linked to increased ad libitum alcohol consumption, but only stimulation of the rDLPFC increased cravings. cTBS of both dorsolateral prefrontal cortices led to reduced inhibitory control. Improvements in mood were observed after a single session of HF-rTMS to the rDLPFC as well as the lDLPFC, but none were noted after one session of cTBS to the rDLPFC, lDLPFC, or medial orbitofrontal cortex (mOFC).

tDCS findings: Two studies investigated the combined effects of tDCS over the lDLPFC with Mindfulness-Based Substance Abuse Treatment (MBSAT) on executive functions (EFs), craving, and negative emotions in individuals with methamphetamine use disorders. Combining tDCS and MBSAT led to significant improvements in cognition, mood, and craving compared to sham stimulation while only tDCS groups also led to improvement with a smaller effect size. A study using a single treatment of bilateral tDCS did not show any effect on alcohol craving, but a case study found that 20 sessions of tDCS over the rDLPFC reduced methamphetamine cravings.

Adverse events/Tolerability Issues: Both interventions were tolerated well with slightly elevated minor adverse reactions such as itchiness/burning sensation, pain, and tingling (tDCS) compared to sham groups.

Conclusion & Discussion: While there is a growing body of evidence for the use of neuromodulatory therapies in the treatment of SUDs in adults, there is very little evidence regarding neuromodulatory treatments in youth. Our results suggest that rTMS and tDCS show promise in addressing the multifaceted challenges facing transitional age youth struggling with addiction. Limitations include the small number of included articles, highlighting the need for further study. Additionally, while our literature searches were extensive, we did not employ a systematic search strategy, which would have strengthened the quality and replicability of our findings. Lastly, the definition of transitional age youth is not uniformly established, with most sources defining the range as 16 –25 , with some sources extending this range even further. One included study had an age range of 16 –27, with a mean of 20.9 and a standard deviation of 2.74. Inclusion of this article allowed for the use of findings highly relevant to transitional age youth as the majority of the sample population fell within the traditionally accepted window. Despite our limitations, our review suggests that neuromodulation has potential in the treatment of transitional age youth SUDs and warrants further investigation.

References: Alizadehgoradel, J., Imani, S., Nejati, V., Vanderhasselt, M. A., Molaei, B., Salehinejad, M. A., Ahmadi, S., & Taherifard, M. (2021). Improved executive functions and reduced craving in youths with methamphetamine addiction: Evidence from combined transcranial direct current stimulation with mindfulness treatment. Clinical Psychopharmacology and Neuroscience, 19(4), 653–668. https://doi.org/10.9758/cpn.2021.19.4.653

Mahoney, J. J., Marshalek, P. J., Rezai, A. R., Lander, L. R., Berry, J. H., & Haut, M. W. (2020). A case report illustrating the effects of repetitive transcranial magnetic stimulation on cue-induced craving in an individual with opioid and cocaine use disorder. Experimental and Clinical Psychopharmacology, 28(1), 1–5.

McNeill, A., Monk, R. L., Qureshi, A. W., Makris, S., & Heim, D. (2018). Continuous theta burst transcranial magnetic stimulation of the right dorsolateral prefrontal cortex impairs inhibitory control and increases alcohol consumption. Cognitive, Affective, & Behavioral Neuroscience, 18(6), 1198–1206. https://doi.org/10.3758/s13415-018-0631-3

McNeill, A. M., Monk, R. L., Qureshi, A. W., Makris, S., Cazzato, V., & Heim, D. (2022). Elevated ad libitum alcohol consumption following continuous theta burst stimulation to the left-dorsolateral prefrontal cortex is partially mediated by changes in craving. Cognitive, Affective, & Behavioral Neuroscience, 22(1), 160–170. https://doi.org/10.3758/s13415-021-00940-7

Hone-Blanchet, A., Mondino, M., & Fecteau, S. (2017). Repetitive transcranial magnetic stimulation reduces anxiety symptoms, drug cravings, and elevates 1H-MRS brain metabolites: A case report. Brain Stimulation, 10(4), 856–858. https://doi.org/10.1016/j.brs.2017.03.007