Methamphetamine and cocaine addiction still have no approved medication treatment. According to the National Institute on Drug Abuse, no medication has FDA approval for methamphetamine use disorder or any other stimulant use disorder, leaving clinicians to rely on behavioural approaches alone once a patient walks through the door already dependent on a drug with no pharmacological off-ramp. For clinicians managing patients caught in that gap, the options run out fast. A research team at the University of Virginia in the United States has spent the past several years testing focused ultrasound treatment for addiction, a noninvasive brain technology originally built for tremor and Parkinson’s disease, to see whether it can fill part of that gap for substance use disorders more broadly.
Dr James Mahoney, Associate Professor, Clinical Neuropsychologist, and Director of the Center for Neuromodulation Research at UVA, leads that work. He describes focused ultrasound not as a cure but as an added layer of support that sits alongside standard addiction treatment. As he put it, the technology is “not… something that’s just going to flip the addiction switch off,” but rather “an added component, an added tool in that toolbox” for patients already receiving behavioural therapy or medication.
Targeting the brain’s reward circuit
Focused ultrasound covers a spectrum of uses. High-intensity versions are already approved to ablate brain tissue for tremor and Parkinson’s disease. Other applications open the blood-brain barrier for targeted drug delivery. Mahoney’s team works with a third form, neuromodulation, which adjusts activity in a brain region rather than destroying tissue.
Their primary target is the nucleus accumbens, a structure deep in the brain’s reward circuitry that connects to several other regions involved in craving and compulsive drug use. Dysfunction in this region is thought to play a central role in addiction. Regulating it, Mahoney’s team reasoned, might in turn regulate the wider network it feeds into.
The equipment itself, the Insight tech Exablate system, delivers treatment through a helmet lined with thousands of transducers. Each one sends ultrasound energy from a different angle, and all of them converge on a single point deep in the brain. A session runs roughly one to two hours including setup, and it takes place inside an MRI scanner so clinicians can confirm the beams are landing precisely on target and nowhere else.
During each session, researchers run what they call a cue-reactivity paradigm: patients are shown images of drugs and drug use tailored to their own history of use, and researchers record their response in real time.
Why depth matters
The differences between neuromodulation approaches come down largely to how deep into the brain each one can reach without surgery. Transcranial magnetic stimulation, one of the more established techniques, primarily targets the dorsal prefrontal cortex, a region close to the skull’s surface. Deep brain stimulation can reach structures as deep as the nucleus accumbens, but only by implanting electrodes, which means open surgery and a permanent device. Vagus nerve stimulation works through a different route entirely, modulating brain activity indirectly via the nerve that runs from the brainstem to the abdomen.
Mahoney’s team can reach the same deep subcortical structures as deep brain stimulation, including the nucleus accumbens and the wider network of regions it connects to, without implanting anything or opening the skull. The MRI-guided helmet lets clinicians confirm in real time that the converging beams are landing on the target region and nowhere else. That real-time confirmation is what allows a treatment aimed at a structure buried deep in the brain to stay fully noninvasive.
From a four-person pilot to a bilateral trial
The programme began cautiously. A 2021 pilot study, cleared by the FDA for unilateral treatment, enrolled four participants and started with a lower dose on the left nucleus accumbens before moving to the right side and a higher, “enhanced therapeutic” dose once safety held up. Results were published in Frontiers in Psychiatry, and the FDA signed off on a larger follow-up trial.
That second study treated 16 participants, this time delivering ultrasound to both the left and right nucleus accumbens simultaneously at the therapeutic dose. Fourteen had a primary opioid use disorder; all were polysubstance users, which Mahoney notes is the norm in addiction treatment rather than the exception. The remaining participants had primary methamphetamine or alcohol use disorder without other substance use. All were recruited from a 28-day residential treatment programme in Morgantown, West Virginia, and every participant with opioid use disorder had already been on medication for at least a week before enrolling, a deliberate design choice to standardise the comparison and reflect the trial’s framing of neuromodulation as an adjunct rather than a replacement for medication.
What the craving and outcome data showed
Craving ratings, scored on a 0-to-10 scale, dropped substantially from baseline to one day after treatment, both for opioids and for the other substances participants used. That reduction held through 90 days of follow-up and beyond.
Substance use outcomes followed a similar pattern. Participants who had been using multiple times a week before entering residential treatment were able to sustain extended periods of abstinence through the 90-day mark. Among those who did relapse, the pattern itself looked different: rather than continuing to use until a crisis forced emergency care or detox, several participants reached out to the study team or a peer recovery coach after just one or two isolated instances of use, asking for extra support before things escalated further.
Participants also reported broader shifts beyond craving scores. Several described a change in how drug-related images affected them, saying the pictures took on what Mahoney’s team describes as a more neutral quality that no longer triggered the urge to use, a shift participants themselves found surprising given how long they had been using. Anxiety improved, tolerance reduced, and participants reported better focus, motivation, and involvement in family, work, and education. Researchers found no change in food-related pleasure, which suggests the effect was specific to drug cues rather than a general blunting of reward response.
An adjunct, not a replacement
Mahoney is careful to frame the findings within the limits of what a two-hour, MRI-guided procedure can realistically achieve. The behavioural treatment that runs alongside it, he notes, is what allows patients to process the shift and rebuild an everyday life without drugs. Focused ultrasound does not replace that work. What the early data suggests is that it may make the work more sustainable by lowering the intensity of cravings that often derail recovery in its first, most fragile months.
For a field with few pharmacological options for stimulant use disorders and high relapse rates across the board, that combination, focused ultrasound treatment for addiction paired with existing behavioural and medication care, is the case Mahoney’s early results are starting to build.
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References
Mahoney, J. J., Haut, M. W., Carpenter, J., et al. (2023). Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial. Frontiers in Psychiatry, 14, 1211566.
Mahoney, J. J., Thompson-Lake, D. G. Y., Ranjan, M., et al. (2023). Low-Intensity Focused Ultrasound Targeting the Bilateral Nucleus Accumbens as a Potential Treatment for Substance Use Disorder: A First-in-Human Report. Biological Psychiatry, 94(11), e41-e43.
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