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Some experts promote deep brain stimulation as a lifeline for people struggling with opioid addiction. Others question the hype.
In 2015, Rosalind Daly was going on a family vacation when she walked into her 16-year-old son's room and found him unconscious. Max, her son, had suffered an overdose of opioids and had slipped into a coma after choking on his vomit.
At that point, Max had already been struggling with addiction for three years. He had gone through various treatments: medication, therapy and inpatient programs in both France, the US and the UK. His relapse in July came just days after he returned home from a six-month rehab program. The coma lasted three days and exacerbated his pre-existing movement disorder, making it impossible for him to attend high school. «I couldn't hold a pen without dropping it, or a cup of coffee without spilling it on myself, — he later recalled.
Max's problems with opioids are typical: an estimated 40 to 60% of people with addiction experience a relapse after completing treatment.
Some researchers believe that many of those who experience relapse may suffer from some form of «treatment-resistant» disorder, although the condition is not recognized as an official medical diagnosis.
However, the invasiveness of the procedure and its high cost — typically in the hundreds of thousands of dollars — have been major obstacles for researchers studying its use in addiction. Research in the field is largely limited to small experiments with a few participants, making it difficult to assess the scope of the method and its effectiveness.
Clinicians exploring the use of deep brain stimulation to treat opioid addiction cite success stories like Max's to support the need for further research in this area. However, the path from experimental treatments to mainstream methods remains uncertain.
Drug dependence is a complex and often individualized condition that affects the human brain. The primary neurotransmitter involved is dopamine, which affects motivation, reward seeking, decision-making and other behaviors.
In many people who begin abusing drugs, the neural pathways associated with these behaviors are concentrated in a small area of the brain known as the contiguous nucleus, located in the front and bottom of the brain. As noted by neurobiologist Jasper Heinsbrook of the University of Alabama at Birmingham, this is where thoughts in motion are activated and decisions such as seeking and using drugs are made. It's also the area where changes in neuronal functioning occur when exposed to long-term abuse.
In the early 2000s, neurosurgeons in China began experimenting with removing the contiguous nucleus in patients to help them cope with severe addictions, inspired by animal studies. In 2004, about 1,000 patients at 20 hospitals underwent the surgery. However, China's Ministry of Health suspended the research due to concerns about the procedure's safety and long-term effects.
The lead author of the study, Patrick Bach, noted that despite the more encouraging results of the activated group, the small sample size does not allow for definitive conclusions about statistical significance.
From the outset, problems associated with small study groups and high statistical uncertainty have made it difficult to determine the efficacy of DBS (deep brain stimulation) for opioid use disorders. Studying substance use disorders in preclinical animal models is challenging, making it difficult to evaluate and improve treatments prior to their use in humans. In addition, the high cost, invasiveness, and novelty of DBS make it difficult for clinicians to recruit participants for clinical trials in the necessary numbers to draw reliable conclusions about therapeutic efficacy.
Max considers the surgery a success, although not a panacea. It helped reduce symptoms of depression and cravings for opioids, which he says he has not used recreationally since the surgery. However, it was less effective for his addiction to methamphetamine and cocaine. He reported relapsing in California, where he began using methamphetamine shortly after surgery. Max believes treatment is most effective when combined with attending Alcoholics Anonymous meetings and therapy sessions. «DBS alone, like any other drug treatment, is really not enough»
For people like Max Daly, life with experimental therapies is full of hope, but also uncertainty. After surgery, he faced a serious infection, which led to the electrode being disconnected. Now back in the U.S. for another surgery, he hopes to resume his life. «DBS doesn't just prevent the threat of overdose, it helps restore joy to life» — concludes his mother Rosalind.
Some experts promote deep brain stimulation as a lifeline for people struggling with opioid addiction. Others question the hype.
In 2015, Rosalind Daly was going on a family vacation when she walked into her 16-year-old son's room and found him unconscious. Max, her son, had suffered an overdose of opioids and had slipped into a coma after choking on his vomit.
At that point, Max had already been struggling with addiction for three years. He had gone through various treatments: medication, therapy and inpatient programs in both France, the US and the UK. His relapse in July came just days after he returned home from a six-month rehab program. The coma lasted three days and exacerbated his pre-existing movement disorder, making it impossible for him to attend high school. «I couldn't hold a pen without dropping it, or a cup of coffee without spilling it on myself, — he later recalled.
Max's problems with opioids are typical: an estimated 40 to 60% of people with addiction experience a relapse after completing treatment.
Some researchers believe that many of those who experience relapse may suffer from some form of «treatment-resistant» disorder, although the condition is not recognized as an official medical diagnosis.
However, the invasiveness of the procedure and its high cost — typically in the hundreds of thousands of dollars — have been major obstacles for researchers studying its use in addiction. Research in the field is largely limited to small experiments with a few participants, making it difficult to assess the scope of the method and its effectiveness.
«At that point, you're in a completely different world of claims and scientific facts» — noted anthropologist Danielle Carr of the University of California, Los Angeles. She believes such small studies are of limited value to a general audience. Carr and other researchers question the wisdom of investing resources in unproven methods that, even if successful, are unlikely to be scalable to address the opioid crisis, which claims more than 100,000 lives in the U.S. each year.
Clinicians exploring the use of deep brain stimulation to treat opioid addiction cite success stories like Max's to support the need for further research in this area. However, the path from experimental treatments to mainstream methods remains uncertain.
Drug dependence is a complex and often individualized condition that affects the human brain. The primary neurotransmitter involved is dopamine, which affects motivation, reward seeking, decision-making and other behaviors.
In many people who begin abusing drugs, the neural pathways associated with these behaviors are concentrated in a small area of the brain known as the contiguous nucleus, located in the front and bottom of the brain. As noted by neurobiologist Jasper Heinsbrook of the University of Alabama at Birmingham, this is where thoughts in motion are activated and decisions such as seeking and using drugs are made. It's also the area where changes in neuronal functioning occur when exposed to long-term abuse.
In the early 2000s, neurosurgeons in China began experimenting with removing the contiguous nucleus in patients to help them cope with severe addictions, inspired by animal studies. In 2004, about 1,000 patients at 20 hospitals underwent the surgery. However, China's Ministry of Health suspended the research due to concerns about the procedure's safety and long-term effects.
Since then, a new technology has emerged that allows us to change the functioning of the brain without having to remove it. Deep brain stimulation (DBS), which began to be researched in the 1980s, has been shown to be effective in treating a variety of movement disorders. Psychiatrist Alik Widge of the University of Minnesota shares about a patient with essential tremor who experienced instant relief, «The patient began to cry tears of joy when his disabling symptom disappeared in an instant, as if he had been cured».
The Food and Drug Administration has approved DBS to treat a number of movement disorders, including essential tremor and Parkinson's disease, and has also created a humanitarian exception for the treatment of obsessive-compulsive disorder. Researchers such as neurosurgeon Casey Halpern of the University of Pennsylvania have begun using DBS for a wider range of mental disorders, including opioid addiction.
The results so far have not been unequivocal. In the late 2010s, two randomized trials of DBS for treatment-resistant depression, involving more than a hundred participants, showed no significant differences between groups. The studies were stopped due to lack of conclusive data. In 2022, Halpern conducted a study with two participants to evaluate the use of DBS to treat compulsive overeating, and participants reported improved self-control and weight loss.
The Food and Drug Administration has approved DBS to treat a number of movement disorders, including essential tremor and Parkinson's disease, and has also created a humanitarian exception for the treatment of obsessive-compulsive disorder. Researchers such as neurosurgeon Casey Halpern of the University of Pennsylvania have begun using DBS for a wider range of mental disorders, including opioid addiction.
The results so far have not been unequivocal. In the late 2010s, two randomized trials of DBS for treatment-resistant depression, involving more than a hundred participants, showed no significant differences between groups. The studies were stopped due to lack of conclusive data. In 2022, Halpern conducted a study with two participants to evaluate the use of DBS to treat compulsive overeating, and participants reported improved self-control and weight loss.
The lead author of the study, Patrick Bach, noted that despite the more encouraging results of the activated group, the small sample size does not allow for definitive conclusions about statistical significance.
From the outset, problems associated with small study groups and high statistical uncertainty have made it difficult to determine the efficacy of DBS (deep brain stimulation) for opioid use disorders. Studying substance use disorders in preclinical animal models is challenging, making it difficult to evaluate and improve treatments prior to their use in humans. In addition, the high cost, invasiveness, and novelty of DBS make it difficult for clinicians to recruit participants for clinical trials in the necessary numbers to draw reliable conclusions about therapeutic efficacy.
A few years ago, researchers at the University of Amsterdam began a pilot study to evaluate DBS as an intervention for opioid addiction. They tried to recruit participants from six institutions that treated about 27,000 patients annually. However, over the three years of the study, only 23 referrals were received, and only two patients agreed to participate. Interviews with patients who were not included in the study showed that fear of surgery was a reason for not participating.
In small trials, it is difficult to determine whether a patient's improvement is due specifically to DBS and not to counseling or other traditional treatments they receive at the same time as DBS, or to the placebo effect — the patient's belief that the procedure is effective, regardless of the actual performance of the electrodes.
Some patients may receive DBS off-label: a doctor who is already using DBS to treat FDA-approved disorders such as movement disorders sometimes suggests implanting an additional electrode to control addictive impulses.
In small trials, it is difficult to determine whether a patient's improvement is due specifically to DBS and not to counseling or other traditional treatments they receive at the same time as DBS, or to the placebo effect — the patient's belief that the procedure is effective, regardless of the actual performance of the electrodes.
Some patients may receive DBS off-label: a doctor who is already using DBS to treat FDA-approved disorders such as movement disorders sometimes suggests implanting an additional electrode to control addictive impulses.
Max considers the surgery a success, although not a panacea. It helped reduce symptoms of depression and cravings for opioids, which he says he has not used recreationally since the surgery. However, it was less effective for his addiction to methamphetamine and cocaine. He reported relapsing in California, where he began using methamphetamine shortly after surgery. Max believes treatment is most effective when combined with attending Alcoholics Anonymous meetings and therapy sessions. «DBS alone, like any other drug treatment, is really not enough»
The same year that Daly received his implant, neurosurgeon Ali Rezaei of West Virginia University launched the first NIH-funded clinical trial to evaluate the effectiveness of DBS for opioid addiction. The project involves recruiting about 20 patients with histories of repeated opioid overdoses and monitoring their drug use and cravings through urine tests and interviews.
Last year, the team released results for the first four participants: two were completely abstinent for more than a year after surgery; one had his implant removed for not following the study protocol; and a fourth participant returned to sporadic drug use, including fentanyl, methamphetamine and cannabis, mostly in moments of unemployment or homelessness. This participant noted that the treatment did not reduce his cravings for opioids.
The diversity of treatment outcomes in early DBS studies for opioid addiction underscores a difficult reality for researchers: positive results for one patient do not guarantee success for others.
«We should seriously consider what one high-profile case study that demonstrates success might mean» — noted Carr of the University of California, Los Angeles, who focuses her work on laboratories studying DBS. She expressed concern about narratives, both in the media and among some researchers, that exaggerate the power of DBS to solve public health problems based on one person's experience.
The diversity of patient outcomes underscores a difficult reality for researchers: promising results for one patient do not necessarily predict success for others.
Last year, the team released results for the first four participants: two were completely abstinent for more than a year after surgery; one had his implant removed for not following the study protocol; and a fourth participant returned to sporadic drug use, including fentanyl, methamphetamine and cannabis, mostly in moments of unemployment or homelessness. This participant noted that the treatment did not reduce his cravings for opioids.
The diversity of treatment outcomes in early DBS studies for opioid addiction underscores a difficult reality for researchers: positive results for one patient do not guarantee success for others.
«We should seriously consider what one high-profile case study that demonstrates success might mean» — noted Carr of the University of California, Los Angeles, who focuses her work on laboratories studying DBS. She expressed concern about narratives, both in the media and among some researchers, that exaggerate the power of DBS to solve public health problems based on one person's experience.
The diversity of patient outcomes underscores a difficult reality for researchers: promising results for one patient do not necessarily predict success for others.
Critics say DBS is unlikely to be a solution to the public health crisis caused by opioid addiction. The treatment is extremely expensive, requires highly trained professionals and is likely to be available to only a few patients who could benefit from it, as noted by neuroethicist Wayne Denis Hall, professor emeritus at the University of Queensland.
Hall and other experts in addiction research believe that trying to make DBS a one-size-fits-all treatment for resistant forms of addiction is misplaced prioritization. They suggest that public health funds and efforts would be better spent on resources such as medications to prevent overdoses and therapy for more patients.
DBS «should not be considered a first-line therapy» — said the researchers from the University of Alabama at Birmingham, viewing the procedure as a last resort that should be resorted to when it may be the only way to prevent overdose deaths. They added that while the surgery is considered generally safe, implanting foreign bodies into the brain carries risks, including inflammation and scarring.
Hall and other experts in addiction research believe that trying to make DBS a one-size-fits-all treatment for resistant forms of addiction is misplaced prioritization. They suggest that public health funds and efforts would be better spent on resources such as medications to prevent overdoses and therapy for more patients.
DBS «should not be considered a first-line therapy» — said the researchers from the University of Alabama at Birmingham, viewing the procedure as a last resort that should be resorted to when it may be the only way to prevent overdose deaths. They added that while the surgery is considered generally safe, implanting foreign bodies into the brain carries risks, including inflammation and scarring.
Bach, who participated in a recent study of DBS for the treatment of alcohol-related disorder, supports further research on this technique in the context of treating substance dependence. He agrees that the current evidence is not strong enough for use outside of clinical trials, but emphasizes the importance of gathering evidence for patients in whom other treatment options have been exhausted. DBS may be useful for such patients, as it is necessary to balance the high mortality from non-disease with the risks of the procedure itself.
Widge, a psychiatrist at the University of Minnesota, notes that small studies and individual successes help reveal the safety and potential of DBS. Each positive result makes it easier to support further research that may lead to new clinical insights. The priority is to understand the reasons for differences in patient response to treatment, which will avoid unnecessary surgeries.
«There is much hope for DBS for addiction treatment, and most experts would agree on the biological plausibility of the idea» — Widge writes, adding that it has not yet been proven clinically or mechanistically.
Halpern sees each study as a step toward understanding addiction as a neurological disease rather than a moral failing. «By using an electrode in the brain, we're helping a patient with opioid addiction, which confirms that it's a brain disorder and not just a weakness of will» — he says.
While opioid-dependent patients are often reluctant to expose themselves to the risks of DBS, some evidence suggests that this may be changing. Widge's team surveyed 20 people with addictions in 2020 and 2021, and most initially expressed discomfort, finding the method «weird» or «scary». However, after discussing the topic, only one participant remained opposed to DBS.
Widge, a psychiatrist at the University of Minnesota, notes that small studies and individual successes help reveal the safety and potential of DBS. Each positive result makes it easier to support further research that may lead to new clinical insights. The priority is to understand the reasons for differences in patient response to treatment, which will avoid unnecessary surgeries.
«There is much hope for DBS for addiction treatment, and most experts would agree on the biological plausibility of the idea» — Widge writes, adding that it has not yet been proven clinically or mechanistically.
Halpern sees each study as a step toward understanding addiction as a neurological disease rather than a moral failing. «By using an electrode in the brain, we're helping a patient with opioid addiction, which confirms that it's a brain disorder and not just a weakness of will» — he says.
While opioid-dependent patients are often reluctant to expose themselves to the risks of DBS, some evidence suggests that this may be changing. Widge's team surveyed 20 people with addictions in 2020 and 2021, and most initially expressed discomfort, finding the method «weird» or «scary». However, after discussing the topic, only one participant remained opposed to DBS.
For people like Max Daly, life with experimental therapies is full of hope, but also uncertainty. After surgery, he faced a serious infection, which led to the electrode being disconnected. Now back in the U.S. for another surgery, he hopes to resume his life. «DBS doesn't just prevent the threat of overdose, it helps restore joy to life» — concludes his mother Rosalind.