Brain Implants to Treat Addiction Are Dangerous and Promising

High Wire is Maia Szalavitz's reported opinion column on drugs and drug policy.

When a researcher suggested that Gerod Buckhalter have experimental brain surgery to treat his addiction, the 33-year-old former hotel worker jumped at the chance.

He had misused opioids since he’d been sidelined by a football injury in high school, later adding Xanax and other benzodiazepines to his mix. He’d already been through dozens of different treatment programs, often dropping out and relapsing the same day. He desperately wanted to change his life.

“Yeah, yeah, of course,” he told James Mahoney, who is assistant professor of neuropsychology at West Virginia School of Medicine and part of his treatment team, “Anything that I could possibly do to give me a better chance at recovery, I’m all about it.”

But Mahoney and his colleagues wanted to be sure he considered his choice carefully. “I'm very impulsive,” he said, “I'll make a decision right now without thinking it through—good or bad. Just all about doing.”

Impulsivity is a common characteristic of addiction, of course. It presents an ethical dilemma to those who study it, especially in the case of experimental treatments like brain surgery that carry serious risks.

And so, before he was cleared to have the operation last November, Buckhalter went through numerous evaluations and consent procedures, to ensure that he really knew the potential dangers and was making a free choice to participate in the pilot program, which is the first in the U.S. and will include four patients. It's a phase one trial of the device, which is the first step toward FDA approval and is focused primarily on safety, rather than whether the therapy itself works.

Such oversight will be crucial to prevent the kinds of ethical problems and abuses that have marred both addiction treatment and mental-health-related brain surgery for many decades—and to determine whether these surgeries should be part of the field’s future.

The operation he underwent—which involves implanting a device that electrically stimulates the brain directly—has been used to treat other conditions for several decades. Known as “deep brain stimulation” (DBS), the implant can be placed in different parts of the brain to treat Parkinson’s disease, obsessive compulsive disorder (OCD) and depression. (It's FDA-approved for Parkinson's and OCD and used off-label for depression.)

Worldwide, some 200,000 patients have had this operation, mainly for Parkinson’s, in which it reduces tremor and movement disorders. The main risk is that of any brain surgery: a 1 percent chance of death or serious, irreversible disability related to stroke, bleeding in the brain and/or infection. That might sound low—but as we’ve seen during the COVID-19 crisis, small risks spread over large populations can cause huge damage. No one would fly a plane with a 1 percent risk of crashing unless there were no safer alternatives in an emergency.

Consequently, taking such extreme measures to treat addiction is controversial, especially when there are less-invasive treatments proven to reduce death risk. Further, opioid addiction is criminalized, highly stigmatized and most existing treatment centers don’t even use the approaches that are scientifically supported. If people haven't been able to try several evidence-based treatments more than once, they shouldn't jump right to surgery.

To top it all off, the use of brain surgery to treat addiction and other psychiatric disorders has a terrible history. This goes back to the 1930s, when people with mental illness, addiction or even just juvenile delinquency were treated with lobotomies. These were sometimes performed on an outpatient basis with a device inspired by an icepick—and they left thousands of people permanently disabled.

More recently, in 2004, Chinese government had to ban a procedure—which had already been used on thousands of people with addictions and mental illnesses—that literally burned away parts of the brain regions involved in desire and pleasure.

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Nonetheless, there are some genuinely intractable cases of addiction, in which even the best treatments have failed repeatedly, leaving people at high risk of death from overdose. Buckhalter, for instance, had at least two overdoses serious enough to require reversal with the antidote, naloxone.

His surgeon, Ali Rezai, executive chairman of the West Virginia University Rockefeller Neuroscience Institute, stressed that DBS surgery should be a last-resort option—only for people for whom evidence-based treatments have repeatedly failed. But the procedure could provide important insights into the nature of addiction.

Buckhalter was the first patient in the U.S. to have the operation for opioid and benzodiazepine addiction. In Canada, noted AIDS researcher Frank Plummer had the surgery in December 2018. He had an alcohol use disorder so severe that he drank after having a liver transplant.

The operation appeared to be successful in allowing Plummer to drink moderately for more than a year. This January, he told the BBC that after his procedure, within weeks “life just became so much better, so much richer." The 67-year-old died in February, but the cause of death has not been made public.

At least nine patients with opioid addiction have been treated in China, with five of them remaining abstinent for at least three years of follow-up. Two relapsed after six months and there is one report of an overdose death three months after the surgery.

“For us, it has to be done very rigorously,” said Rezai, acknowledging the complexity of addiction, which typically co-occurs with other mental illnesses and often leaves people without the support systems needed to handle surgery.

“It took us two years to initiate this study,” he said, adding that it was funded by the National Institute on Drug Abuse and had numerous layers of oversight, both within and outside the university.

Finding patients who, like Buckhalter, have both treatment-resistant addiction and a home and family able to help him through the surgical process and recovery is also difficult. Severe addiction tends to either remove those supports or be moderated by them—people with both extremely stable living situations and extremely bad addictions are rare.

But Rezai and his colleagues persisted, in part because of the success they’ve seen with DBS for intractable OCD, which is similar in many ways to addiction. In OCD, people repeat ritual behaviors like handwashing or counting so often that it interferes with their ability to function: The desire to engage in the behavior is as compelling as the drive to do drugs is in people with addictions.

Both conditions trap people in a loop: patients believe they must engage in their preferred behavior in order to feel safe and relieve anxiety, even as it takes over their lives and they recognize that it does more harm than good. Further, both disorders involve craving and impulsivity. Patients find it difficult to resist the problematic behavior because it feels like an automatic and emotionally necessary response to certain experiences.

Dysfunction in the brain's nucleus accumbens, which is part of the striatum, is seen in both OCD and addictions—so this is the area that is targeted. While the region is typically described as the “pleasure center,” it is far more complicated and is also linked with desire, motivation and, in severe OCD and addiction, a craving for relief through repetition. In both conditions, the same neurotransmitters and the same part of the striatum are implicated.

“It seems clear the compulsive aspects of addiction strongly overlap with those in OCD, and both are [mediated] by changes in activity in the striatum and surrounding areas,” said Marc Lewis, a neuroscientist who himself has suffered from opioid addiction and is author, most recently, of The Biology of Desire.

He added, “The torment of OCD [and] the torment of addiction makes it well worthwhile to try DBS. Given the fairly low risk of death or serious medical mishaps, why not? OCD is real shit…and, well, addiction is no picnic either.”

But the operation is not all that is required: patients need to continue with behavioral treatment like talk therapy and support groups as they learn other coping methods and the device is tuned and begins to work. The stimulation also has to be adjusted specifically for each person. Too much can produce a euphoric, almost manic state and too little may not lift depression or reduce cravings.

In Buckhalter’s case, his addiction had been driven by anxiety, depression and an inability to experience much pleasure. The surgery itself wasn’t unmanageable, even though he had to be awake for much of it in order to ensure that the placement of the implant wouldn’t damage crucial regions. He was anesthetized while the surgeons drilled into his skull and stabilized his head in a cage-like structure known as a halo.

“When I woke up from that, that was probably the scariest moment,” he said. During the actual procedure, the surgical team soothed and distracted him. The worst part was the pain he had when he woke up afterwards, he said. But it passed quickly and he recovered well.

The first time the device was activated, Buckhalter said that he felt “really, really, really, really good.” A day later, that euphoria receded. When it was further adjusted, he said that he simply felt the way he did when he wasn’t addicted, anxious or depressed.

With the exception of normal anxiety in appropriate situations like public speaking, he explained, “I don't have any anxiety anymore. And I'm the farthest [I’ve ever been] from being depressed.” He’s currently working with other patients at the treatment center at the university, which he greatly enjoys—although it may have to be done online during the pandemic.

“Before, you know, I just didn't do anything,” Buckhalter said, “Nothing brought joy to my life.” But now, he takes pleasure in ordinary, good experiences and both his impulsivity and his cravings have been reduced. “Once in a great while, I'll have a few cravings. They don't last very long and they're not so strong that I contemplate acting on them…before I couldn't process thinking of the consequences,” he said. But now he can.

The tuning of the DBS device can present weird ethical questions: in some sense, the doctor determines how good the patient’s ordinary mood should be. While this problem can also arise in the treatment of depression and addiction with medications, it raises difficult issues about power and agency.

Sometimes the doctor and patient disagree. In one instance, a German OCD patient felt that his doctor should have increased the stimulation, but the doctor thought the device was set too high and they had to settle on a setting in between.

In another case, a woman treated for chronic pain was given direct control over her own device (this is not done currently). She wound up stimulating herself so often that she had heart problems and did little else for two years, essentially developing an addiction. She described the experience as “erotic” and began ignoring her family and failing to bathe. She pushed the button on the stimulator so frequently that she developed an open sore on the finger she used to press it. Interestingly, the 48-year-old had previously had a problem with alcohol and opioids.

Because of the implant, researchers can study Buckhalter’s brain in a way that can’t be done otherwise. They can record activity in the regions associated with pleasure and desire, which are deep in the center of the brain and, as a result, very difficult to research in humans.

“[DBS] can potentially be critical in terms of coming up with a biomarker that can be linked to increased addictive behavior,” Rezai said. That knowledge could be useful in the development of drugs or other therapies that are less demanding than brain surgery.

“If we demonstrate that it's not safe or feasible, we'll stop,” Rezai said, “If this phase one is successful, then we will go into phase two, which will be a randomized controlled trial.”

Patients at the extremes of addiction—who have repeatedly been failed by good treatment, are also motivated enough to go through brain surgery and on top of that, have consistent family or spousal support and a safe place to live—are extremely unusual. This means that DBS is unlikely to ever be a common treatment.

However, if it is shown to work in a controlled trial, it could be an option for those who might otherwise have hopeless cases. Or, it might provide researchers with evidence that allows the development of better medications or less invasive stimulation—one such approach called transcranial magnetic stimulation, which uses magnetic fields to stimulate neurons from outside the skull, is already being tested.

In Buckhalter’s case, his opioid addiction had been brought under control by buprenorphine (Suboxone) before the operation—but he simply could not stop taking benzodiazepines, despite that treatment. This is especially risky in combination with opioids because these drugs magnify overdose risk.

Consequently, even after the surgery, he has stayed on buprenorphine, because of its proven effects in reducing opioid overdose death risk by 50 percent or more. If he were to relapse on benzodiazepines or street opioids—many of which are contaminated with fentanyl these days—he would be far more likely to die without the buprenophine’s effect in maintaining opioid tolerance.

“I'll cross that bridge when I get to it,” he said, “I just don't want to change anything that's working for me right now.”

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