Written by: Amanda Dankberg
Edited by: Kaitlin Lemke
Edited by: Kaitlin Lemke
The opioid overdose epidemic is worsening in the United States. Fortunately, researchers are developing new technologies to aid in the recovery of opioid addicts and stop addiction, permanently. One such promising technology is repetitive transcranial magnetic stimulation (rTMS), which aims to repair dopamine pathways in the brain to modulate substance cravings while avoiding the side effects of current treatment drugs and being accessible to everyone.
Why is combating the opioid crisis important? Every year, 10.3 million people misuse prescription opioids, resulting in over 130 deaths every day. Additionally, once an addiction starts, intense cravings and dependency develop.
From a neuroscience perspective, addiction is accompanied by neuroplastic changes in the brain’s reward circuitry that furthers addiction and leads to more relapses. Opioid addiction affects the receptors involved in both ascending and descending neurological pathways. Cravings are modulated by the prefrontal cortical and limbic projections and back projections. The mesolimbic reward system in the central nervous system plays a key role. Dopamine, a brain chemical involved in the feelings of reward and pleasure, is generated in the lower brain areas and then moves to the cortex. The limbic structures – the parts of the brain involved in behavior and emotions such as survival instincts – are modified to perpetuate addiction. Opioids inhibit a dopamine inhibitor, causing dopamine to be released in overwhelming amounts.
The most common options to treat addiction are currently behavioral therapy and medication. However, behavioral therapy is often ineffective and has high rates of relapse. Medications have higher rates of efficacy but have side effects, including vomiting, cognitive troubles, fainting, chest pain, confusion, tooth decay, muscle aches, rash, and more. These treatments are also not always accessible for various groups of people, including patients who live in areas without clinic access, specific professional groups (ex. pilots and healthcare workers), and patients with challenging personal circumstances. Additionally, there still exists a stigma with using medication, as many perceive using medication to treat addiction as replacing one opioid with another. Thus, researchers have sought to create a more accessible and effective treatment: rTMS.
rTMS uses electromagnetic stimulation of neuronal populations in the central nervous system to modulate substance cravings; specifically, rTMS stimulates the prefrontal cortex with a pulsed magnetic field. When the magnetic field crosses through cortical neurons, it entrains with the frequency of the electromagnetic pulse of the brain. This elevates the depressed frontal cortex, which can treat many neuropsychiatric symptoms.
Over time, rTMS recalibrates dopamine transmission, treats hedonic dysregulation (phasic cravings) caused by addiction, and has immune effects that decrease inflammation in the brain to help repair dopamine pathways. In addition, during opioid withdrawal, dopamine drastically decreases – rTMS can increase dopamine levels in healthy amounts during these times. One key advantage of rTMS is that it easily crosses the blood-brain barrier, a challenge faced by drug development. rTMS also treats depression and anxiety, both of which are symptoms that often accompany opioid addiction. Furthermore, patients do not have to endure brain or systemic side effects. In a small pilot study, all patients stopped heroin use after the use of rTMS therapy.
Although rTMS has been in use for a while, the machine is quite large and expensive, which still presents issues with accessibility. Thus, Dr. Makale and his team at the University of California San Diego are currently working to miniaturize it to the point where it could potentially be worn underneath a hat and used in daily life without much hassle. Additionally, miniaturization could have the advantage of facilitating coil integration with current EEG (electroencephalogram) sensors, which would create a highly effective closed loop. Essentially, this could lead to real-time modulated treatment systems that can be worn for semi-continuous ambulatory treatment.
However, extreme miniaturization is no easy task. rTMS is extremely high in both voltage and current, requiring a quick circuit discharge to elicit an electric field in the brain. In reality, this may lead to overheating and scalp pain. So far, a successful benchmark prototype has been able to achieve 300 volts/meter in only 1.5 centimeters and 20 grams – such innovative strides are certainly promising. In addition, there have been experiments with energy recycling to prevent overheating; this prototype currently has the power to do one 10-minute cycle every day and is now going into its first clinical trial.
If trials are successful, rTMS can be used for more than just addiction – for instance, it was evident in the first pilot study that it can drastically reduce depression and anxiety. Other positive effects of rTMS include an overall boost in brain activity, alertness, and even vision. It has been utilized in U.S. military studies, which it was proven to increase accuracy and aim. It has also been used in sports to improve performance and treat head injuries, such as concussions. Finally, in studies done on U.S. veterans, it was shown to alleviate symptoms of PTSD. Essentially, if this miniaturized version of rTMS proves to be effective and widely accessible, it could have significant impacts on both society and the medical industry.
References
Makale, M. T. (2023, January). Towards a Wearable rTMS Device to Suppress Cravings in Opioid Use Disorder. Lecture, Los Angeles; UCLA.
Naltrexone. SAMHSA. (n.d.). Retrieved April 5, 2023, from https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-rela ted-conditions/naltrexone
Why is combating the opioid crisis important? Every year, 10.3 million people misuse prescription opioids, resulting in over 130 deaths every day. Additionally, once an addiction starts, intense cravings and dependency develop.
From a neuroscience perspective, addiction is accompanied by neuroplastic changes in the brain’s reward circuitry that furthers addiction and leads to more relapses. Opioid addiction affects the receptors involved in both ascending and descending neurological pathways. Cravings are modulated by the prefrontal cortical and limbic projections and back projections. The mesolimbic reward system in the central nervous system plays a key role. Dopamine, a brain chemical involved in the feelings of reward and pleasure, is generated in the lower brain areas and then moves to the cortex. The limbic structures – the parts of the brain involved in behavior and emotions such as survival instincts – are modified to perpetuate addiction. Opioids inhibit a dopamine inhibitor, causing dopamine to be released in overwhelming amounts.
The most common options to treat addiction are currently behavioral therapy and medication. However, behavioral therapy is often ineffective and has high rates of relapse. Medications have higher rates of efficacy but have side effects, including vomiting, cognitive troubles, fainting, chest pain, confusion, tooth decay, muscle aches, rash, and more. These treatments are also not always accessible for various groups of people, including patients who live in areas without clinic access, specific professional groups (ex. pilots and healthcare workers), and patients with challenging personal circumstances. Additionally, there still exists a stigma with using medication, as many perceive using medication to treat addiction as replacing one opioid with another. Thus, researchers have sought to create a more accessible and effective treatment: rTMS.
rTMS uses electromagnetic stimulation of neuronal populations in the central nervous system to modulate substance cravings; specifically, rTMS stimulates the prefrontal cortex with a pulsed magnetic field. When the magnetic field crosses through cortical neurons, it entrains with the frequency of the electromagnetic pulse of the brain. This elevates the depressed frontal cortex, which can treat many neuropsychiatric symptoms.
Over time, rTMS recalibrates dopamine transmission, treats hedonic dysregulation (phasic cravings) caused by addiction, and has immune effects that decrease inflammation in the brain to help repair dopamine pathways. In addition, during opioid withdrawal, dopamine drastically decreases – rTMS can increase dopamine levels in healthy amounts during these times. One key advantage of rTMS is that it easily crosses the blood-brain barrier, a challenge faced by drug development. rTMS also treats depression and anxiety, both of which are symptoms that often accompany opioid addiction. Furthermore, patients do not have to endure brain or systemic side effects. In a small pilot study, all patients stopped heroin use after the use of rTMS therapy.
Although rTMS has been in use for a while, the machine is quite large and expensive, which still presents issues with accessibility. Thus, Dr. Makale and his team at the University of California San Diego are currently working to miniaturize it to the point where it could potentially be worn underneath a hat and used in daily life without much hassle. Additionally, miniaturization could have the advantage of facilitating coil integration with current EEG (electroencephalogram) sensors, which would create a highly effective closed loop. Essentially, this could lead to real-time modulated treatment systems that can be worn for semi-continuous ambulatory treatment.
However, extreme miniaturization is no easy task. rTMS is extremely high in both voltage and current, requiring a quick circuit discharge to elicit an electric field in the brain. In reality, this may lead to overheating and scalp pain. So far, a successful benchmark prototype has been able to achieve 300 volts/meter in only 1.5 centimeters and 20 grams – such innovative strides are certainly promising. In addition, there have been experiments with energy recycling to prevent overheating; this prototype currently has the power to do one 10-minute cycle every day and is now going into its first clinical trial.
If trials are successful, rTMS can be used for more than just addiction – for instance, it was evident in the first pilot study that it can drastically reduce depression and anxiety. Other positive effects of rTMS include an overall boost in brain activity, alertness, and even vision. It has been utilized in U.S. military studies, which it was proven to increase accuracy and aim. It has also been used in sports to improve performance and treat head injuries, such as concussions. Finally, in studies done on U.S. veterans, it was shown to alleviate symptoms of PTSD. Essentially, if this miniaturized version of rTMS proves to be effective and widely accessible, it could have significant impacts on both society and the medical industry.
References
Makale, M. T. (2023, January). Towards a Wearable rTMS Device to Suppress Cravings in Opioid Use Disorder. Lecture, Los Angeles; UCLA.
Naltrexone. SAMHSA. (n.d.). Retrieved April 5, 2023, from https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-rela ted-conditions/naltrexone
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