Neuromodulation (Brain Stimulation) Technologies for Treatment of Substance Use Disorders
Authors: Souki Afra , Soleimani Ghazaleh , Hanlon Colleen , Ekhtiari Hamed 
Published: January 2024

This chapter traces the historical development of brain stimulation technologies and their methodological parameters for treating substance use disorders (SUDs). These methods include Transcranial Electrical Stimulation (tES), Transcranial Magnetic Stimulation (TMS), Deep Brain Stimulation (DBS), and Transcranial Focused Ultrasound Stimulation (tFUS). The application of magnetic stimulation in modulating addictive behaviors dates back to the development of TMS for cigarette smoking around 2003 and later for cocaine use disorders around 2007. The development of electrical devices paralleled the early use of direct current stimulation in electrical medicine, starting around 2008 for alcohol and nicotine use disorders. Throughout the twentieth century, electrical medicine evolved, with increasingly sophisticated electronics allowing for new technologies utilizing complex waveforms (first transcranial alternating current stimulation (tACS) trial in SUD in 2020). Additionally, the first report investigating the effects of low-intensity tFUS neuromodulation for SUDs was published in 2023, demonstrating safety and significant decreases in cravings for all substances. The first systematic reviews on the application of tES and TMS for SUDs were conducted in 2012, indicating that these noninvasive brain stimulation technologies could be promising options in addiction treatment. More than 80% of previous brain stimulation studies targeted the dorsolateral prefrontal cortex, intending to modulate regions associated with pathophysiological excitability. However, there was significant variability between and within studies in terms of experimental design and individual responses to brain stimulation for addiction and meta-analyses reported small to medium effect sizes for the effectiveness of these technologies in SUDs. By the end of 2018, only 84 published tES/TMS trials were conducted in the field of SUDs. By the end of 2022, this number had increased to 198 studies. Following a decade of rapid growth, the United States Food and Drug Administration (FDA) cleared TMS for smoking cessation (FDA: K200957) in 2020. Since then, there has been an accelerating pace of new clinical trials using novel tools and protocols of non-invasive neuromodulation for SUDs, and the list of devices and indications receiving CE marking in Europe is growing. Over the last decade, systematic exploration of the dose-response and individual variability in brain stimulation methods has suggested new approaches to optimize responses. In recent years, there has been rapid growth and expansion of non-invasive neuromodulations as circuit-based interventional tools in SUD research. In 2023, trials emerged using fMRI-informed individualized brain stimulation for SUDs, utilizing fMRI data to inform brain stimulation parameters. This chapter introduces different types of brain stimulation methods for SUDs, emphasizing the unique role of tES and TMS in altering the broader trajectory of brain stimulation research for SUDs. The methodological parameter space and incremental approach have been foundational in outstanding tES/TMS studies, serving as a scientific anchor for the broader (re)discovery of non-invasive brain stimulation in this field.