Repetitive transcranial magnetic stimulation (rTMS) is an exciting therapeutic modality for the treatment of Substance Use Disorders (SUDs). Recent developments regarding the efficacy and safety of rTMS for several manifestations of SUDs and concurrent disorders are encouraging.
SUDs are among the leading cause of morbidity and mortality worldwide. The epidemic of opioid addiction and mortality in the U.S. is a clarion call for action. Our understanding of the neurobiology of SUDs has advanced exponentially, in part because of new brain imaging technology developed over the past three decades. However, treatment options remain woefully limited.
Both animal and human imaging studies have revealed previously unknown circuits that mediate various phases of addictive disease. The ventral tegmental area (VTA) and ventral striatum, including the nucleus accumbens (NaC), are innervated during intoxication. The extended amygdala in the midbrain becomes overactive during periods of forced abstinence and during withdrawal from most intoxicants, producing a highly negative affect. The neural circuitry innervating the orbitofrontal cortex-dorsal striatum, prefrontal cortex is impaired during acute intoxication and degraded by chronic administration of psychoactive substances (addiction). The basolateral amygdala, hippocampus and insula are activated during high stress and anxious states, and are thus involved in drug and alcohol craving states.
If disrupted inhibitory control in the dorsolateral prefrontal and inferior frontal cortices (which are part of the pathophysiology of SUD) occur, the rick of relapse increases dramatically. While this complicated and intricate biochemistry is currently better understood than ever before, targeting these critical brain regions and functions with therapeutic agents are often futile due to the tightly knit endothelial barrier that guards the brain from foreign or toxic substances.
However, recent studies have demonstrated the potential of transcranial magnetic stimulation (TMS) as an innovative, safe and cost-effective treatment for SUDs that is not prevented by the Blood Brain Barrier (BBB).
How Does Transcranial Magnetic Stimulation Work?
Transcranial magnetic stimulation (TMS) is a noninvasive procedure originally developed for treatment-resistant depression. We were among the first to use it when it was approved for use by the FDA at the University of Florida’s hospitals and clinics. The patients liked the treatments, plus it was easy to use, safe and effective.
TMS uses magnetic fields to stimulate nerve cells in the brain to improve dysphoric symptoms associated with depression and now SUDs, which share much the same pathophysiology and bi-directionally co-occur in 45-65% of patients with either disorder. TMS treats depression, but it is also being tried as a treatment for pain, cigarette smoking, tinnitus and memory.
For addiction, TMS or (rTMS) influences neural activity and neuroplasticity, both locally, directly under the stimulating coil, and systemically, by improving neural connectivity that has been degraded by SUDs throughout the brain. The limited research on SUDs and rTMS suggest that long-term neurophysiological changes induced by the magnets may mediate behaviors relating to drug craving, intake and relapse. The best available research suggests that rTMS is opening novel modalities in addiction treatment.
Why Does This Matter?
In a very short time, all drugs of abuse cause neuroadaptive changes in the brain’s dopamine and related reward systems. Today, we cannot guarantee that the patient, even if they stop using drugs and work very hard at a relapse prevention program, will return to their premorbid state. This is due in part to the fact that intoxicants are taken to cause euphoria and a state of well-being. They target the brain and insinuate themselves into similarly sized, shaped and specific neurotransmitters. Drug-receptor and brain systems are at first activated by their interaction but over time become changed and overwhelmed.
Drugs are effective counterfeits for the real neurotransmitters, often damaging and degrading the neuronal connectivity and signals between important nuclei in the dopamine reward system and throughout the brain. Drugs of abuse raise the brain’s reward threshold, meaning that more stimulation is needed for former addicts to feel pleasure.
Because of the aforementioned barriers to chemical therapeutics, non-drug treatments such as TMS have been added to aid in reprogramming the brain’s circuitry, releasing endorphins and other brain neurotransmitters, and promotion of neuroadaptive changes to the damaged circuitry.
This exciting new modality is not unlike the work that Herb Kleebler, Fred Goodwin, other scientists at National Institute of Mental Health (NIMH) and I did in the early 1980s, when we developed our hypothesis that opioid abuse and addiction induced endogenous opioid deficiencies. It did indeed. If TMS releases endogenous opioids, as shown by Naltrexone reversal of analgesia, the benefits would be a very important finding, to say the least.
My recent research with Dr. Ben Srivastava at Washington University, which was published in Current Psychiatry, asked the question of how many drug overdoses were accidental and how many were suicide attempts. Depression, suicidal thinking and anhedonia are all real and important acquired problems that accompany drug abuse and addictions. On the question of depression versus poisoning versus accidental opioid overdoses, we point to the lack of overall efficacy of current pharmacological treatments, most of which induce neurotoxicity – this is just more evidence for the need of TMS and related restorative treatments.