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Substance use disorder afflicts many Americans — in 2021, 46.3 million people in the United States age 12 or older were addicted to alcohol or drugs such as opioids and stimulants. Now scientists are studying a promising and surprisingly familiar therapy that can help reset the brain and stem the cravings of addiction.

The treatment is low-intensity focused ultrasound or LIFU, a noninvasive brain stimulation therapy. Researchers at the University of Virginia are running the first pilot study to evaluate the effectiveness of ultrasound to treat cocaine use disorder. Nearby at the West Virginia University School of Medicine, ultrasound is being studied to primarily treat opioid use disorder, but also addiction to a number of substances including patient cravings for a number of substances, including alcohol, cannabis, methamphetamine and cocaine.

Early findings among a few initial patients have been promising, but more research is needed. “The most impressive thing about this is the potential for sustained changes from just a 10-to-20-minute treatment,” said James Mahoney, a clinical neuropsychologist at West Virginia University helping conduct the research.

If effective, LIFU could be an important tool for helping patients that current therapies are failing and be used as a treatment for various forms of addiction, including smoking and alcohol use disorder as well as opioid, heroin and cocaine addiction.

Other forms of brain stimulation therapy have been used to tackle addiction with varying results. The benefit of low-intensity focused ultrasound is that it’s non-invasive and doesn’t require anesthesia.

The specific mechanism underlying how <a href="https://www.mdpi.com/2076-3425/12/5/611" target=_blank>brain stimulation therapies</a> work is unclear. But they are believed to regulate the flow of messaging molecules between neurons, called neurotransmitters, effectively resetting the brain, “so that individuals are not influenced by their severe cravings and anxiety that’s driving them to get the cocaine or get the opioids,” said Ali Rezai, a professor of neurosurgery at West Virginia University School of Medicine.

There are various brain stimulation techniques.

Electroconvulsive therapy (ECT) was developed nearly a century ago. In ECT, a patient under anesthesia has an electric current sent through their brain, causing a brief seizure. <a href="https://www.fda.gov/news-events/fda-brief/fda-brief-fda-takes-action-ensure-regulation-electroconvulsive-therapy-devices-better-protects" target=_blank>ECT is</a> still used today, for instance, in major depressive disorder, schizophrenia and bipolar disorder. ECT is not typically used for substance use disorders.

For certain mental health conditions, “ECT is remarkably effective,” said Diana Martinez, a professor of psychiatry at Columbia University. But, she said, in addition to requiring anesthesia, ECT can cause temporary memory impairment, which many patients understandably dislike.

Deep brain stimulation (DBS), used to treat a number of <a href="https://www.elsevier.es/en-revista-neurology-perspectives-17-avance-resumen-deep-brain-stimulation-in-neurological-S2667049622000278#:" target=_blank>conditions</a>, including Parkinson’s disease and obsessive compulsive disorder (OCD), requires the implantation of a neurostimulator — similar to a cardiac pacemaker — that delivers electrical pulses to a patient’s brain. DBS is highly effective, and over 200,000 people across the globe have received these implants, but an invasive brain surgery can be a major detractor.

Transcranial magnetic stimulation (TMS), which uses magnetic pulses to stimulate cells in the brain, does not require anesthesia or surgery and has been approved to treat major depressive disorder and OCD.

TMS has shown potential for treating substance use disorders, but a significant drawback is that the magnetic fields it produces cannot precisely target the deep brain structures involved in addiction, so other structures end up being stimulated as well.

Unlike TMS, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208465/" target=_blank>low-intensity focused ultrasound</a> can precisely target structures deep in the brain, using mechanical, acoustic energy.

“You can direct ultrasound beams to a precise, pinpointed area,” Rezai said. LIFU is being evaluated for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032970/" target=_blank>coma</a> recovery, <a href="https://innovationdistrict.childrensnational.org/lifu-successfully-delivers-targeted-therapies-past-the-blood-brain-barrier/" target=_blank>brain</a> cancer, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612615/" target=_blank>Alzheimer’s disease</a> and addiction, targeting various brain regions.

In their University of Virginia study focused on cocaine addiction, researchers will target the insular cortex. The insular cortex — located deep within the brain — is believed to play a central role in the <a href="https://www.sciencedirect.com/science/article/abs/pii/S1364661315001035#sec0040" target=_blank>reward circuitry</a> involved in substance use disorders. “It’s really almost a gatekeeper,” for the reward system because it’s involved in <a href="https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(20)30238-1#:" target=_blank>interoception</a> — the receiving, interpreting and regulating of signals sent from different regions of the body, said Nassima Ait-Daoud Tiouririne, associate professor of psychiatry and neurobehavioral sciences at the University of Virginia School of Medicine.

She and her colleagues will assess the safety and efficacy of LIFU for reducing cravings in 30 patients with cocaine use disorder. Participants in the study will be placed in a functional MRI (fMRI) machine — which measures changes in blood flow throughout the brain, indicating brain activity — and then shown images of cocaine, cocaine use and paraphernalia such as pipes and needles, and asked to rate their craving.

The participants will next be given either the LIFU treatment targeting the insular cortex or what is called a<a href="https://www.atsjournals.org/doi/full/10.1513/pats.200707-090JK" target=_blank> sham treatment</a>, where the person administering the treatment goes through the motions but no energy is delivered to the brain.

The patients will then be placed back in the fMRI, exposed to the same images as before and asked to again rate their craving. Those ratings will be important but so will the fMRI data, because it will show if brain activity is altered by the LIFU treatment, Ait-Daoud Tiouririne said.

“We’re looking at connectivity of the brain because what we know with addiction, it’s not just one part of the brain,” she said.

The study is particularly important because currently the only treatment available for cocaine use disorder is behavioral therapy. An estimated 1.4 million people in the United States struggled with cocaine use disorder in 2021.

Rezai and Mahoney are also <a href="https://pubmed.ncbi.nlm.nih.gov/37779628/" target=_blank>evaluating LIFU</a> for treating addiction, but they are targeting the nucleus accumbens. The nucleus accumbens is a structure that, like the insular cortex, is deep in the brain and implicated in addiction.

They have only published <a href="https://www.biologicalpsychiatryjournal.com/article/S0006-3223(23)01405-1/fulltext" target=_blank>two</a> <a href="https://pubmed.ncbi.nlm.nih.gov/37779628/" target=_blank>studies</a> for a total of five patients, but Mahoney said that patient cravings for a number of substances, including alcohol, heroin and cocaine, did not just temporarily decrease; the effect lasted even 90 days later.

LIFU to treat substance use disorders currently is not being considered as a first-line therapy, but as another important tool for treating addiction, Mahoney said. “It’s not meant to just flip the addiction switch,” he said. “It’s not meant to replace the standard of care treatments, but rather be used in combination.”

Rezai said it will probably be for people who have had multiple attempts at treatment, “and despite that, they’re struggling with their addiction.”

One day, though, it could be a first-line measure for fighting the addiction crisis, said Martinez, who believes it could play an important role in alleviating some of the burden on the psychology and psychiatry fields where there is a <a href="https://www.aamc.org/news/growing-psychiatrist-shortage-enormous-demand-mental-health-services" target="_blank">provider shortage</a>. People could receive LIFU therapy early on, which might make them “more able to respond to behavioral treatment,” she said.

“The addiction problem is not going away,” said Rezai. “It’s only getting worse.”

Do you have a question about human behavior or neuroscience? Email <a href="mailto:brainmatters@washpost.com">BrainMatters@washpost.com</a> and we may answer it in a future column.

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Brain ultrasound may offer hope for people with addiction disorders

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An illustration of an arrow piercing a small bag of cocaine with the headline: Can brain ultrasound treat addiction? A cocaine study may hold answers.

Can brain ultrasound treat addiction? A cocaine study may hold answers.

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