Neuromodulation in Addiction Treatment

When most people consider treatment for psychiatric problems, they usually consider medications and/or psychotherapy. However, emerging neuromodulation approaches using transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), low-intensity focused ultrasound (LIFU), and deep brain stimulation (DBS) may also treat substance use disorders (SUDs). In different ways, these high-tech treatments directly target addiction neurocircuitry in the brain.

In 2007, Antoine Bechara and colleagues published a groundbreaking study in Science highlighting the role of the damaged insula cortex in smoking addiction. This article provided unique insights into neural circuits underlying addiction, spurring research into potential therapeutic targets for SUDs. For example, patients experiencing strokes or lesions in the insula cortex often described losing the urge to smoke, suggesting the insula plays a critical role maintaining interoceptive awareness of cravings and addiction-related behaviors. This study was one of the first to establish the insula cortex as a critical hub for addiction, particularly in processing craving-related emotional/bodily states. It also suggested addiction may be caused by an imbalance in brain systems among individuals with SUDs. Correcting that imbalance might offer new hope for patients.

Considering TMS and tDCS

With transcranial magnetic stimulation (TMS), an electric pulse generator connected to a magnetic coil is placed on the scalp, creating a magnetic field. This induces an electric current in brain tissue, changing neuronal and brain activity. It does not require sedation or surgery.

TMS is used primarily in psychiatry and neurology, particularly for treatment-resistant depression. It is FDA-approved for depression and is more effective than antidepressants in patients unresponsive to medication. It is also FDA-approved for treating obsessive-compulsive disorder (OCD), as well as anxiety disorders, bipolar depression, post-traumatic stress disorder (PTSD), and cigarette smoking cessation. TMS is under study for ADHD, bipolar disorder, Parkinson’s disease, chronic pain, and migraines. TMS is used in dual diagnosis treatment if depression persists during or after primary addiction treatment. Today, neuromodulation therapies are being tried for primary addiction, too.

Early researchers observed that TMS could modulate addiction-related brain regions, such as the dorsolateral prefrontal cortex (DLPFC)—crucial for decision-making, impulse control, and craving regulation. With smoking cessation, several studies demonstrated TMS targeting the left DLPFC reduced nicotine cravings and withdrawal symptoms. After clinical trials, the BrainsWay H4 coil system TMS was approved for smoking cessation.

More recently, TMS targeting the DLPFC also has shown efficacy in reducing alcohol craving and consumption and has been approved in some countries for alcohol use disorders (AUD). Recently, Harel et al. demonstrated 15 sessions of daily high-frequency, targeting the dorsal anterior cingulate cortex (dACC) and dorsomedial prefrontal cortex (dmPFC) using the H7 Brainway coil over three weeks, led to greater alcohol abstinence relative to sham in individuals with AUD.

Use in cocaine and psychostimulant disorders is inconsistent, requiring more extensive clinical trials. Evidence also suggests reduced gambling urges and improved control over compulsive behaviors after DLPFC stimulation.

TMS is believed to modulate dopamine release, restoring inhibitory control by enhancing prefrontal cortex activity and reducing hyperactivation of craving-related regions like the insula.

Another form of neuromodulation, transcranial direct current stimulation (tDCS) modulates neuron excitability using low-level electrical currents delivered through electrodes on the scalp. It has been tried with many SUDs, but the best data is for stimulation of the dorsolateral prefrontal cortex (DLPFC) in reducing alcohol craving and consumption. In another approach, tDCS could prime the brain by modulating cortical excitability before applying TMS to target specific circuits more effectively. This approach requires further investigation.

Deep Brain Stimulation

Deep brain stimulation (DBS) stimulates the brain directly during brain surgery and is the most invasive procedure. Helen S. Mayberg, M.D., of Mt. Sinai in New York is a neurologist renowned for studying brain circuits in depression and for her pioneering DBS research. Mayberg’s circuit-based approach to mental health disorders has inspired addiction researchers to explore DBS in targeting reward-related circuits like the nucleus accumbens (NAc) and the prefrontal cortex. Mayberg, a global pioneer in DBS for treatment-resistant depression, has provided insights into the role of the subcallosal cingulate (Area 25) in depression. She described this region as “at the hub of all the brain’s tracks that can wreak havoc on all the core systems affected by major depression.”

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In discussing the rationale behind using DBS, Dr. Mayberg explained, “We knew we wanted activity in our circuit and particularly Area 25 to be turned down or blocked. We knew if you couldn’t talk it or drug it or shock it into remission, maybe you could surgically modulate it.”

Looking at DBS and LIFU

The WVU Rockefeller Neuroscience Institute (RNI) has been pioneering DBS to address opioid use disorder (OUD) and other severe addictions, particularly for patients unresponsive to conventional treatments. Patients selected for this DBS trial previously had undergone numerous failed interventions, including rehabilitation and medication-assisted therapies, and faced high risks of overdose and relapse. The trial also explored underlying brain mechanisms of human addiction and how DBS may modulate brain circuits and, consequently, compulsive drug-seeking behaviors. These trials led WVU to a non-invasive NM alternative: low-intensity focused ultrasound (LIFU).

LIFU is both a technology and an application in medical treatment. LIFU is gaining attention for its safety, precision, and potential to replace or complement more invasive neuromodulation techniques like DBS. The method uses highly targeted ultrasound waves to concentrate energy on specific brain regions, such as the nucleus accumbens, in the case of opioid use disorder (OUD). This precision allows the modulation of brain activity in deep structures without surgery. LIFU influences neuronal activity by stimulating or inhibiting specific brain regions. It’s a promising treatment for addiction, chronic pain, and depression.

In a recent pilot study, West Virginia University researchers applied LIFU to participants with substance use disorders. The findings indicated LIFU was safe and well-tolerated, with participants experiencing acute reductions in substance cravings during the procedure and potential longer-term craving reductions.

Director of addictions, professor, and chairman of psychiatry Dr. James Berry told me, “Given the positive findings we are seeing with our low-intensity ultrasound for OUD, we have put DBS on the back burner. Although our DBS findings are encouraging, based on our early research, LIFU has the potential to transform our therapeutic toolbox as we are seeing a dramatic decrease in substance use and cravings for opioids and other substances. Since this is a non-invasive procedure, it has the potential to be much more accessible than treatment requiring brain surgery.”

Summary

Neuromodulation techniques like TMS, tDCS, LIFU, and DBS are being tested to rebalance brain circuits and activity and help treat addictions. TMS is used to treat co-existing addiction and psychiatric disorders but may also have a more significant role in primary addiction treatment to improve self-control and reduce cravings and relapse. TMS might help re-balance the brain circuits that drug addiction has interrupted, modified, and changed. TMS is approved to treat nicotine dependence, but more trials are necessary in other SUDs. Non-invasive LIFU targeting the brain’s NAc or ventral striatum has been explored recently for opioid and alcohol use disorders, building on insights from DBS and progress in understanding brain circuitry underlying addictions.