Frank Plummer’s research has helped save the lives of countless others. Now, the microbiologist and infectious-disease expert is helping scientists test an experimental treatment that may save his own.
Dr. Plummer, an Officer of the Order of Canada whose work, particularly in HIV/AIDS, has shaped prevention strategies internationally, is the first participant in a Toronto trial that is using deep-brain stimulation to treat alcohol-use disorder. The treatment is sometimes described as a pacemaker for the brain. A year ago, surgeons implanted two electrodes in his brain – and the tiny, electric pulses they constantly emit, he said, have helped him feel better than he has in more than a decade.
“It’s given me my life back," he told The Globe and Mail recently. “I have a lot more joy for life.”
Dr. Plummer said he relied on alcohol over the years to deal with daily life, from stress to grief to happiness. Since alcohol use is common and socially accepted, and because he limited his consumption to evenings after work, he did not realize his drinking was problematic until he learned his liver was failing in 2012.
Today, he said, he is not completely abstinent – that is not his goal – although he no longer drinks every day and does not crave it. With his newfound energy, he is writing a book and working on developing an HIV vaccine.
A former scientific director of the National Microbiology Laboratory in Winnipeg involved in the development of an Ebola vaccine, Dr. Plummer is the first patient with alcohol-use disorder to participate in the trial at Sunnybrook Health Sciences Centre; researchers are hoping to get a total of six. It is believed to be the first trial of deep-brain stimulation for alcohol-use disorder in North America.
While deep-brain stimulation has been used to treat chronic pain since the 1970s, the list of conditions for which it is used either clinically or experimentally has grown to include Parkinson’s disease, depression, anorexia nervosa, post-traumatic stress disorder and addiction disorders. In November, researchers in West Virginia performed surgery on their initial participant in the first U.S. trial of deep-brain stimulation for opioid-use disorder.
The procedure involves drilling small holes in the skull to place electrodes into targeted areas of the brain, while a battery pack that powers them is implanted under the collarbone.
In Dr. Plummer’s case, electrodes were placed in the nucleus accumbens, a part of the brain that plays a major role in the reward system and communicates with other areas involved in decision-making and mood. The latter is important as alcohol-use disorder is often tied to depression.
“The idea is that if we can stimulate this part of the brain, disrupt the activity in the [brain’s reward] circuit and essentially reset it, we may have a good chance of having an influence and impact on some of these behaviours” involved in alcohol-use disorder, said neurosurgeon Nir Lipsman, the lead investigator of the Sunnybrook trial.
This approach reflects a shift in thinking about alcohol-use disorder, which affects an estimated 8 per cent of Canadians, as being driven by circuits in the brain that are not functioning properly.
“It’s among the most stigmatized illnesses there are,” Dr. Lipsman said, adding that many, including in the medical community, still view the disorder as a choice, a lifestyle or a weakness. By contrast, he said, “We view it as no different from Parkinson’s disease or Huntington’s disease or tremor, or any of these motor-circuit conditions. … These are circuit-based disorders of the brain.”
In the U.S., Ali Rezai, lead investigator of the trial for opioid use disorder at West Virginia University, said the nucleus accumbens is a key brain structure targeted in deep-brain stimulation studies for various types of addictions, whether to a drug, an activity such as gambling or eating, or a combination of substances.
Dr. Rezai explained that the cycle of addiction unfolds as follows: An individual starts using a substance, then he or she begins misusing the substance, before becoming dependent on it. Eventually, this evolves into an addiction.
“It’s not a brain disorder to begin with, but it becomes a brain disorder over time,” he said, adding that there are multiple contributing factors including genetics, individual and family dynamics, peer interactions and a lack of access to treatments, particularly in the early stages.
Many studies indicate that the nucleus accumbens becomes impaired in addiction, and there appears to be heightened activity in the reward circuits of the brain, contributing to cravings, Dr. Rezai said. Research suggests that there is also a corresponding decrease in activity in the prefrontal cortex, a part of the brain involved in controlling behaviour.
While the exact mechanisms of deep-brain stimulation are still unknown, the goal is to address this imbalance to improve individuals’ behavioural self-control, Dr. Rezai said.
Existing treatments for substance use disorders, such as medication, counselling and cognitive behavioural therapy, can be very effective, but it is important for individuals to have access to these treatments early and often to prevent or minimize changes occurring in the brain, he said.
Since deep-brain stimulation requires surgery, which involves risks such as infection and bleeding, it should only be reserved for severe, “end-stage” situations, where other forms of treatment have not worked, he said.
In the Toronto trial, volunteers are only considered if they have tried many other forms of treatment. The researchers believe deep-brain stimulation may allow patients to have a better chance of benefiting from these standard treatments, thus participants continue to receive counselling or participate in rehabilitation programs after surgery.
Treatment doesn’t end with deep-brain stimulation, Dr. Lipsman said, it begins with it.
Dr. Plummer continues to participate in an after-care program. His family feels a weight has been lifted, said his wife Jo Kennelly, who added that she often felt blamed as an enabler of his drinking.
“With this, I’m an abler in his recovery,” she said. “There’s no blame from the nucleus accumbens.”
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