Neuromodulation for Treating Substance Use Disorders

While medications for addiction treatment (MAT) and behavioral therapies are the primary treatment options for substance use disorders (SUDs), neuromodulation interventions have emerged as promising new treatments. These non-invasive therapies use electrical, magnetic, or ultrasound to alter the activity of neural circuits in the brain involved in reward and motivation and implicated in addiction (Oesterle et al., 2025). The goal is to directly influence brain function to reduce craving, improve self-control, and help reset the brain’s reward pathways, which have been altered by repeated substance use.   

The Science Behind Addiction and Neuromodulation

SUD is a chronic disease affecting parts of the brain involved in judgment, decision-making, learning and memory, and behavior (NIDA, 2020). Repeated exposure to drugs or alcohol overstimulates critical neurocircuits, leading to the release of artificially high levels of neurotransmitters like dopamine, which over time weakens the brain’s natural reward response and the prefrontal cortex’s ability to regulate impulse control and decision-making (Volkow et al., 2019).

Neuromodulation refers to non-invasive medical interventions using electrical,  magnetic, or ultrasound stimulation to target brain activity impacted by addiction (Oesterle et al., 2025). These therapies aim to directly stimulate these key regions in the brain, such as the prefrontal cortex (which manages decision-making and impulse control) and the nucleus accumbens (the brain’s “reward hub,” which has a significant role in motivation, pleasure, and reinforcement learning), and help reset the brain’s natural reward pathways to reduce craving and improve self-control. 

Neuromodulation has been developed and tested to address neurological and psychiatric disorders, including Parkinson’s disease, Alzheimer’s disease, obsessive-compulsive disorder, depression, and chronic pain (Coles et al., 2018; Mehta et al., 2024). Research shows stimulating specific areas of the brain can help restore more balanced activity and strengthen communication between brain regions involved in behavior, emotion, movement, and self-control (Coles et al., 2018; Bari et al., 2018; Mehta et al., 2024). 

Neuromodulation for Addiction Treatment

Researchers are now exploring neuromodulation as a treatment for SUDs. Early studies show encouraging reductions in craving and relapse risk, but the science is still in early stages, with most studies including a small number of individuals, short-term follow-up, and variations in treatment procedures. 

Below is an overview of the types of neuromodulation techniques being studied and what the latest research reveals about their potential benefits.

Repetitive Transcranial Magnetic Stimulation (rTMS)

How It Works

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique that uses magnetic pulses delivered through an electromagnetic coil placed on the scalp to activate specific brain regions, particularly the prefrontal cortex. These magnetic pulses directly produce measurable changes in brain activity, either increasing or decreasing neural activity, depending on the frequency used. Through repeated sessions, rTMS can strengthen neural pathways in underactive regions affected by addiction (e.g., areas responsible for self-control and emotional regulation), while suppressing overactive reward circuits that drive cravings.

What the Research Shows

Findings from a 2024 literature review and meta-analysis, which included 51 rTMS-specific studies and involving 2,406 participants, showed (Mehta et al., 2024):

• rTMS had positive outcomes in reducing craving and/or substance use across tobacco, stimulants (cocaine and methamphetamine), and opioid use disorders. 

• For alcohol use disorder treatment, rTMS studies showed promising results, with many studies showing multi-sessions produce significantly greater reduction in both craving and drinking frequency compared to single-sessions. However, some studies reported mixed results, which researchers note may be due to differences in stimulation parameters, treatment duration, and intensity, and small sample sizes across studies.

• Overall, high-frequency stimulation and repeated sessions were especially effective, while single-session protocols showed little benefit.

These findings are consistent with earlier published literature reviews, showing rTMS can effectively and safely alter craving intensity and self-control, though effects tend to diminish over time without follow-up sessions (Coles et al., 2018). In another review, researchers noted that non-invasive stimulation techniques—including rTMS and Transcranial Direct Current Stimulation (tDCS)—are currently the most supported by evidence for the treatment of substance use disorders (Oesterle et al., 2025). rTMS has also received FDA approval for smoking cessation. 

Transcranial Direct Current Stimulation (tDCS)

How It Works

Transcranial Direct Current Stimulation (tDCS) is another non-invasive technique that applies a low-intensity electrical current through electrodes on the scalp to subtly alter brain activity. The process involves two or more electrodes, placed on either side of the scalp, that provide positive currents to increase activity, or negative currents produce the opposite. Instead of directly activating neurons, it adjusts their responsiveness, making them slightly more or less likely to respond to other inputs, such as craving or impulse control. 

What the Research Shows

The same 2024 literature review and meta-analysis, which included 36 tDCS studies and 1,582 participants, found tDCS has promising but less consistent effects than rTMS (Mehta et al., 2024). Findings include: 

• tDCS studies have shown similar efficacy to rTMS in the treatment of tobacco, stimulant, and opioid use disorders, helping to reduce cravings and substance use, while alcohol studies have shown less consistent results.

• tDCS appeared most effective when delivered in longer sessions (greater than 10-15 minutes) and over multiple treatment days. 

Across other reviews, tDCS consistently showed modest but meaningful improvements in craving and self-control, especially for tobacco, alcohol, stimulant, and opioid use disorders (Coles et al., 2018; Oesterle et al., 2025). However, the evidence base remains less robust than for rTMS. In addition, most studies were short-term, involved small samples, and lacked standardized protocols (Coles et al., 2018; Mehta et al., 2024). 

Deep Brain Stimulation (DBS)

How It Works

Deep brain stimulation (DBS) involves a surgical procedure that places thin electrodes into specific regions of the brain to deliver continuous electrical pulses. These signals help correct abnormal neural activity in specific parts of the brain. DBS uses high frequencies to block neural transmissions through specific areas, whereas rTMS and tDCS activate or inhibit targeted areas. 

What the Research Shows

In another systematic review, researchers synthesized 26 studies involving 71 participants treated with DBS for alcohol, opioid, stimulant, and tobacco use disorders (Zammit Dimech et al., 2024). Findings from these studies include: 

• Across all studies, nearly 27% of patients remained abstinent throughout the follow-up periods (which ranged from 100 days to 8 years), while nearly half (49.3%) showed significant reductions in substance use and/or sustained periods of abstinence.

• Nearly all studies reported participants experiencing reductions in cravings, and some also reported improved mood and quality of life.

• Most notably, 50% of participants who received DBS to treat opioid use disorder and nearly 67% of participants who received the treatment for methamphetamine use disorder remained abstinent during follow-up.    

• Researchers emphasized that these studies were mostly small pilot trials with sample sizes averaging 3-7 participants. 

Other research affirms DBS holds promise for substance use disorder treatment, but remains experimental due to cost, surgical risk, and limited availability(Mehta et al., 2023; Oesterle et al., 2025). In addition, researchers believe DBS is best suited for individuals with severe substance use disorders or who are not responding to conventional treatment options (Zammit Dimech et al., 2024). 

Focused Ultrasound (FUS)

How It Works

Focused ultrasound (FUS) neuromodulation uses low-intensity sound waves, precisely targeted through the skull and guided by MRI, to adjust deep brain structures without surgical implantation. This process primarily targets the parts of the brain associated with reward and craving circuitry. This technique works to rebalance communication between the brain’s reward systems and the regions that control decision-making and self-control, helping to reduce cravings, substance use, and the risk of relapse. 

What the Research Shows

A 2025 pilot study tested FUS in eight participants with severe opioid use disorder. After a single 20-minute session, results showed (Rezai et al., 2025):  

• Participants showed an average of 91% reduction in opioid cravings from baseline to 90 days post-treatment

• Nearly 88% of participants were abstinent at 30 days following, and 62.5% remained abstinent at three months.

• Brain scans showed that the technique was safe, well-tolerated, and showed normalized brain connectivity.

Although at a very early stage, these findings suggest FUS is a feasible, well-tolerated, non-invasive neuromodulation technique with potential for severe SUD cases. The authors note that larger, randomized trials with longer follow-up are needed to confirm how well the treatment works, identify the best parameters for treatment (intensity, duration, target coordinates), and see if it could help with other substances beyond opioids.

Transcutaneous Auricular Neurostimulation (tAN)

How It Works

Transcutaneous auricular neurostimulation (tAN) is a non-invasive neuromodulation technique that has shown to be effective in treating opioid withdrawal symptoms. It involves delivering mild electrical impulses through small electrodes placed on the outer ear. These impulses target key nerve pathways that help regulate stress, heart rate, and relaxation (vagus nerve), and which carry signals related to sensation and facial movement (trigeminal nerve). By activating these nerve pathways, tAN aims to calm the body’s stress response and restore balance in brain activity, easing this discomfort that comes from opioid withdrawal. 

What the Research Shows

In a novel 2022 study, researchers found tAN (Tirado et al., 2022):

• Reduced opioid withdrawal symptoms by 42% within 30 minutes and 46% within one hour. 

• Over days 2-5, participants achieved up to a nearly 75% average reduction in withdrawal symptoms. 

tAN shows strong initial evidence as a safe option for managing opioid withdrawal symptoms without using medication. While these findings are promising, research on the effectiveness of tAN remains in the early stages, with limited data on long-term outcomes and small sample sizes. 

References

Bari, A., DiCesare, J., Babayan, D., Runcie, M., Sparks, H., & Wilson, B. (2018). Neuromodulation for substance addiction in human subjects: A review. Neuroscience and biobehavioral reviews, 95, 33–43. https://doi.org/10.1016/j.neubiorev.2018.09.013

Coles, A. S., Kozak, K., & George, T. P. (2018). A review of brain stimulation methods to treat substance use disorders. The American journal on addictions, 27(2), 71–91. https://doi.org/10.1111/ajad.12674

Mehta, D. D., Praecht, A., Ward, H. B., Sanches, M., Sorkhou, M., Tang, V. M., Steele, V. R., Hanlon, C. A., & George, T. P. (2024). A systematic review and meta-analysis of neuromodulation therapies for substance use disorders. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 49(4), 649–680. https://doi.org/10.1038/s41386-023-01776-0

National Institute on Drug Abuse. (2023). Drugs, Brains, and Behavior: The Science of Addiction. National Institutes of Health. https://nida.nih.gov/research-topics/addiction-science/drugs-brain-behavior-science-of-addiction

Oesterle, T. S., Bormann, N. L., Al-Soleiti, M., Kung, S., Singh, B., McGinnis, M. T., Correa da Costa, S., Rummans, T., Chauhan, M., Rojas Cabrera, J. M., Vettleson-Trutza, S. A., Scheitler, K. M., Shin, H., Lee, K. H., & Gold, M. S. (2025). Invasive and Non-Invasive Neuromodulation for the Treatment of Substance Use Disorders: A Review of Reviews. Brain sciences, 15(7), 723. https://doi.org/10.3390/brainsci15070723

Rezai, A., Thompson-Lake, D. G. Y., D'Haese, P. F., Meyer, N., Ranjan, M., Farmer, D., Finomore, V., Marton, J. L., Hodder, S., Carpenter, J., Bhagwat, A., Berry, J., Tirumalai, P., Adams, G., Arsiwala, T. A., Blanke, O., & Mahoney, J. J., 3rd (2025). Focused Ultrasound Neuromodulation: Exploring a Novel Treatment for Severe Opioid Use Disorder. Biological psychiatry, 98(1), 56–64. https://doi.org/10.1016/j.biopsych.2025.01.001

Tirado, C. F., Washburn, S. N., Covalin, A., Hedenberg, C., Vanderpool, H., Benner, C., Powell, D. P., McWade, M. A., & Khodaparast, N. (2022). Delivering transcutaneous auricular neurostimulation (tAN) to improve symptoms associated with opioid withdrawal: results from a prospective clinical trial. Bioelectronic medicine, 8(1), 12. https://doi.org/10.1186/s42234-022-00095-x

Volkow, N. D., Michaelides, M., & Baler, R. (2019). The Neuroscience of Drug Reward and Addiction. Physiological reviews, 99(4), 2115–2140. https://doi.org/10.1152/physrev.00014.2018

Zammit Dimech, D., Zammit Dimech, A. A., Hughes, M., & Zrinzo, L. (2024). A systematic review of deep brain stimulation for substance use disorders. Translational psychiatry, 14(1), 361. https://doi.org/10.1038/s41398-024-03060-1