Substance Use Disorders (SUDs) are chronic, relapsing, and life-long diseases that, unlike appendicitis, strep throat, or some Cancers, are not cured by current treatments. The goals of treatments for SUDs are harm reduction, remission, and also a return to premorbid functioning. Large numbers of people have SUDs that have elevated relapse rates, even following treatment initiation. Medications have been significant additions to the treatment of SUDs, including medicines for detoxification that decrease craving and prevent overdoses and relapses.
Treatments have improved but, while safe and effective, are not always ideal. Research has suggested that many neurological effects of SUDs persist long after detoxification . Despite our best efforts, many patients have persistent deficits , do not return to premorbid function, and many patients relapse. New research and ideas may help treatment and recovery outcomes by adding to the current standard, safe and effective treatments.
New Treatment Ideas for Substance Use Disorders
New data reported by SUD experts have supported the importance of incorporating vigorous physical exercise as part of SUD treatment and recovery programs . Patients with substance use disorders often have problems with stress management, anxiety, and stress-related relapses. They also have altered neural, behavioral, and physiological responses to stress . Exercise is a treatment and often a mainstay of regenerative medicine and recovery programs.
Eminem  described vigorous physical activity as an essential part of his treatment and continued recovery from his 2007 overdose on opioid pills. He had SUDs and polydrug use and abuse. When he was admitted to the rehab hospital, he was also approximately 230 pounds.
According to him, “When I got out of rehab, I needed to lose weight, but I also needed to figure out a way to function sober. Unless I was blitzed out of my mind, I had trouble sleeping. So I started running. It gave me a natural endorphin high, but it also helped me sleep, so it was perfect.
“It’s easy to understand how people replace addiction with exercise —one addiction for another but one that’s good for them. I got an addict’s brain, and when it came to running, I think I got a little carried away. I became a …. hamster.
“Seventeen miles a day on a treadmill. I would get up in the morning, and before I went to the studio, I would run eight and a half miles in about an hour. Then I’d come home and run another eight and a half. I started getting OCD about the calories, making sure I burned 2,000 every day. In the end, I got down to about 149 pounds . I ran to the point where I started to get injured. All the constant pounding from the running began to tear up my hip flexors.”
While he may be an exception, exercise is a crucial component of treatment and recovery programs these days. By the way, Eminem reports that he is clean and sober for 12 years  and tweeted out his A.A. 12-year sobriety pin.
Recent research by Thanos demonstrated how exercise could alter the brain’s mesolimbic dopamine pathway, linked to the rewarding and reinforcing properties of drugs such as cocaine. Exercise can help prevent relapses into cocaine addiction, according to new research led by the University at Buffalo’s Professor Panayotis (Peter) Thanos, Ph.D.
“Cocaine addiction is often characterized by cycles of recovery and relapse, with stress and negative emotions, often caused by withdrawal itself, among the major causes of relapse,” says Thanos, a senior research scientist in the U.B. Research Institute on Addictions and the Department of Pharmacology and Toxicology in the Jacobs School of Medicine and Biomedical Sciences.
Using animal models, Thanos found that regular aerobic exercise (one hour on a treadmill, five times a week) decreased stress-induced cocaine-seeking behavior. Exercise also altered behavioral and physiological responses to stress .
Exercise has the potential for the prevention and treatment of SUDs and neuropsychiatric diseases. Studies have shown that aerobic exercise is an effective regenerative medicine treatment strategy utilized in Parkinson’s Disease, heart disease, diabetes, anxiety, and depression. “Our results suggest that regular aerobic exercise could be a useful strategy for relapse prevention, as part of a comprehensive treatment program for recovering cocaine abusers,” Thanos says.
“Further research is necessary to see if these results also hold true for other addictive drugs.” Also, exercise reduces stress hormones and elevates mood, which could alleviate anxiety and negative emotions associated with withdrawal. Exercise effects on epigenetics and sex differences are examined and discussed in terms of future research implications .
Neuromodulation: TMS and DBS
Scientists are continuously looking for novel approaches and new modalities for treatment for substance use disorders . Another strategy involves transcranial neuromodulation, which has been used therapeutically for neurological and psychiatric disorders and has demonstrated positive preliminary findings for substance use disorder treatment.
Transcranial Magnetic Stimulation (TMS) is a non-invasive treatment in widespread use for depression. TMS uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression, reduce obsessions and compulsions, and also to reduce cigarette smoking.
It is being tried in SUDs, especially in craving and facilitating brain circuit recovery from drugs of abuse. TMS, unlike vagus nerve stimulation or deep brain stimulation, does not require surgery or implantation of electrodes.
Transcranial Magnetic Stimulation is not electroconvulsive therapy (ECT) and doesn’t cause seizures or require sedation with anesthesia. Generally, rTMS is considered safe and well-tolerated.TMS is widely used by Psychiatrists to treat depression when other depression treatments haven’t been effective.
Potential neuromodulatory treatments for substance use disorder include:
- Transcranial direct current stimulation
- Transcranial magnetic stimulation
- Theta-burst stimulation
- Deep brain stimulation
- Vagal nerve stimulation
- Trigeminal nerve stimulation
- Percutaneous nerve field stimulation
- Auricular nerve stimulation
- Low intensity focused ultrasound
Of these neuromodulatory treatments, Transcranial Magnetic Stimulation (TMS) has many well-designed studies supporting use in tobacco, cocaine, and other SUDs. Excitatory repetitive TMS of the brain’s dorsolateral prefrontal cortex reduces craving and drug use in patients with substance use disorders. The anti-craving effect of TMS neuromodulation may be related to the TMS stimulation dose.
Zhang et al.  found that repetitive excitatory TMS on the top left part of the brain—the dorsolateral prefrontal cortex—significantly decreased substance use and cravings. Another recent review  by Mahoney and colleagues describes the currently available neuromodulation, both invasive and non-invasive, which are being investigated in 2020 to treat SUDs.
The data supporting the use of Transcranial Magnetic Stimulation in SUDs is extensive and compelling. Deep brain stimulation has also shown promise, though it has not been widely studied and lacks well-controlled clinical trials to support its efficacy. It does help us to understand that addiction and recovery are related to brain circuits activation and changes.
Knowing where to stimulate with DBS as such discoveries may directly translate to other less invasive forms of neuromodulation treatments. Transcranial direct current stimulation has also demonstrated promising results though the findings are not consistent, and well-designed randomized clinical trials are needed to prove safety and efficacy.
Mahoney concludes that Transcranial Magnetic Stimulation research and reports are promising and may help reduce substance use and craving. It does appear that neuromodulation may provide a non-pharmacological option as a potential treatment and/or treatment augmentation for substance use disorder . Zhang, Mahoney, and an international consensus panel agree that TMS is both promising and useful treatment for SUDs .
Diet and Nutraceuticals
Cannabidiol or CBD, the non-psychoactive ingredient in hemp and marijuana, could also find a role in the treat opioid use disorders, craving, and addiction . When CBD is given to heroin addicts, it reduced their appetites for illicit drugs and their anxiety levels.
Lead study author Yasmin Hurd, Ph.D.  said, “To address the critical need for new treatment options for the millions of people and families who are being devastated by this epidemic, we initiated a study to assess the potential of a non-intoxicating cannabinoid on craving and anxiety in heroin-addicted individuals.”
Dr. Hurd added, “The specific effects of CBD on cue-induced drug craving and anxiety are particularly important in the development of addiction therapeutics because environmental cues are one of the strongest triggers for relapse and continued drug use .”
Blum  has worked to understand dopamine and Substance Use Disorders for 50 years. His recent work asks whether a pro-dopamine lifestyle with gentle prolonged D2 agonist therapy overcome DNA polymorphisms by promoting positive epigenetic effects. Nutraceutical dietary supplementation might induce current changes but also changes that might be transferred from generation to generation.
Blum has worked for decades on the development of a nutraceutical product to enhance dopamine neurotransmission . Holistic addiction adjunctive dietary treatment modalities like a low glycemic index diet could augment other holistic treatments like exercise, mindfulness training, neurofeedback, yoga, and meditation, all known to support reward neurotransmission and naturally enhance the release of dopamine and thereby reduce craving and relapse.
TMS has been successfully utilized in smoking cessation and craving for cigarette smoking. Mindful yogic breathing also appears to be useful in smoking cessation but primarily in mitigating the withdrawal-related anhedonia and decreasing smoking behavior. Mindful breathing techniques are safe, simple, and cost-effective strategies  worth adding to the treatment of SUDs.
We have made remarkable progress in understanding that SUDs are diseases of the brain and developing new evidence-based treatments for SUDs. These new treatments are safe and effective but best for tobacco, alcohol, and opioid use disorders.
Progress has been much slower for cocaine, methamphetamine, and cannabis use disorders. In these SUDs, the brain changes may resemble traumatic injury or vascular hypoperfusion, causing brain circuit dysfunctions.
Recently reported research clearly shows that not all brain changes produced by drugs are reversed when use is discontinued and may persist for months. New treatments are necessary and are being studied right now. Diet and dietary supplements, exercise, Transcranial Magnetic Stimulation , and brain stimulation appear to be the most promising new adjunctive treatments for SUDs, craving, and relapse.
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About the Author:
Mark S. Gold, M.D., Professor, Washington University School of Medicine – Department of Psychiatry, served as Professor, the Donald Dizney Eminent Scholar, Distinguished Professor and Chair of Psychiatry from 1990-2014. He was the first Faculty from the College of Medicine to be selected as a University-wide Distinguished Alumni Professor and served as the 17th University of Florida’s Distinguished Alumni Professor.
Dr. Gold is also a Distinguished Fellow, American Society of Addiction Medicine; Distinguished Life Fellow, the American Psychiatric Association; Distinguished Fellow, American College of Clinical Pharmacology; Clinical Professor of Psychiatry, Tulane University School of Medicine; Professor( Adjunct), Washington University in St Louis, School of Medicine, Department of Psychiatry; National Council, Washington University in St Louis, Institute for Public Health
Learn more about Mark S. Gold, MD
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Published on October 15, 2020. Published on AddictionHope.com
Reviewed by Jacquelyn Ekern, MS, LPC on October 15, 2020