A surgeon has implanted electrodes in the brain of a patient suffering from severe opioid use disorder, hoping to cure the man’s intractable craving for drugs in the first such procedure performed in the United States.

The device, known as a deep brain stimulator, is designed to alter the function of circuits in the man’s brain. It has been used with varying degrees of success in the treatment of Parkinson’s disease, dystonia, epilepsy, obsessive-compulsive disorder and even depression. It is seen as a last-resort therapy after the failure of standard care, such as medication that reduces the craving for drugs.

The deep brain stimulator, which functions much like a heart pacemaker, was implanted by Ali Rezai, executive chairman of the West Virginia University Rockefeller Neuroscience Institute. His patient, 33-year-old hotel worker Gerod Buckhalter, said he had been unable to remain sober for more than four months since the age of 15, despite trying a variety of medications and other inpatient and outpatient treatments.

Buckhalter is the first of four people in a pilot program, which aims to demonstrate that the technique is safe so that a full-scale clinical trial can be conducted. It is aimed at a small percentage of opioid abusers with the most treatment-resistant cravings for opioids, who may face a lifetime of overdoses, relapses, inability to hold a job and other consequences of addiction.

The seven-hour surgery was performed Friday and the school announced it Tuesday.

“I’m not advocating for deep brain stimulation as a first line or a second line (treatment),” Rezai said. “It’s for people who have failed everything, because it is brain surgery.”

Rezai’s surgical team opened a hole in Buckhalter’s skull about the size of a nickel, then inserted four wires into his nucleus accumbens, a part of the brain’s reward system that responds strongly to opioids. Except when the hole was being cut in his skull, Buckhalter was awake and providing feedback throughout the procedure, Rezai said.

By sending a pulsed current through the electrodes, doctors believe they can regulate an imbalance in Buckhalter’s reward circuitry. The intervention also may prevent his condition from worsening, Rezai said. Under normal circumstances, his cravings might continue to become stronger, he said.

The wires run from the stimulator, about the size of a pocket watch, and a battery, which were implanted behind Buckhalter’s collar bone, to his brain. Using wireless technology, doctors will adjust the current going through the electrodes to provide more or less stimulation to the nucleus accumbens, depending on Buckhalter’s needs.

Rezai acknowledged that doctors and researchers do not yet fully understand how this works.

“The exact mechanisms are not known,” he said. By modulating the reward circuit, which relies on a chemical messenger called dopamine, “you’re getting better control, so you’re not craving dopamine as much,” he said.

The same type of surgery for other diseases has relieved debilitating symptoms, including the motor problems experienced by Parkinson’s patients. About 180,000 people around the world have deep brain stimulators, Rezai said.

The same surgery for people with opioid use disorder has been performed in China and Holland, said Helen Mayberg, director of the Center of Advanced Circuit Therapeutics at Mt. Sinai Medical Center’s Icahn School of Medicine, and also has been tried as a cure for alcoholism.

Other countries have employed different approaches for people with the most severe addictions as the opioid crisis continues. In Canada, for example, a few small programs offer hardcore heroin addicts a pharmaceutical grade version of the drug so they can function.

Rezai’s effort is believed to be the first attempt to use deep brain stimulation on opioid use disorder in the United States. It is partly funded by the National Institute on Drug Abuse and required approval from, among other agencies, the U.S. Food and Drug Administration.

Nora Volkow, NIDA’s director, said she spoke with a handful of the patients who underwent the procedure in China and concluded that the surgery had potential. They told her that after the operation, they were no longer consumed by the need to acquire drugs and were able to pay attention to other things.

“They reported more of an ability to engage, to feel interest in other things,” she said. The brain’s fixation on opioids may have been disrupted by the surgery, she said.

Mayberg, who was not involved in the trial, said the logic of the effort is sound, and the circuitry of this part of the brain is well-mapped compared with other regions. The key question is whether the researchers have found the precise spot for insertion of the electrodes.

“The precision of where you put it is key,” she said. “Different nodes are good for different kinds of problems, because circuits are abnormal in different ways.”

Monday, December 09, 2019