Project Summary/Abstract Cannabis is used by up to half of the U.S. >1 million people living with the neurologic condition of multiple sclerosis (MS), which is the most common chronic and progressive CNS disease to affect adults of working age. Growing evidence shows that cannabis use actually worsens MS disability for many, and specifically contributes to the commonly (>75%) disabling feature of cognitive impairment. However, for the many patients seeking to reduce or discontinue their use, there are few if any accessible interventions available, leaving both clinicians and investigators to only counsel for its discontinuation. To meet this critical need, our expert team connects our extensive work in the use of noninvasive brain stimulation in MS to its established applications in the treatment of substance use disorders. Although the neural circuitry contributing to this cycle of addiction is well known, there are no neural circuit based therapeutics available for cannabis use disorder (CUD) treatment. We propose a novel and readily scalable approach that is highly accessible due to its telehealth delivery that allows all study procedures to be completed form home. Our innovative approach will use repeated sessions of transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) as a target of negative affect that is identified as a key component in perpetuating disordered substance use. A core feature of Koob & Volkow’s 3-stage model of addiction, negative affect both results from disordered use and drives continued use. We therefore hypothesize that reducing distress in this context will lead to reduced cannabis use. We overcome a major limitation in the clinical evaluation of tDCS to date with our remote protocol, enabling access to treatment and providing extended treatments for adequate evaluation of its cumulative benefits. We will recruit a readily available sample of patients with MS and CUD, to evaluate 20 daily (M-F) sessions over one month, using RS-tDCS as a tool to decrease distress (Aim 1) and reduce cannabis use (Aim 2). As tDCS is ideally paired with a concurrent activity to increase benefit and to maintain consistent “brain state” to evaluate its effects, stimulation will be paired with guided mindfulness meditation. In the context of this evaluation, we will collect cognitive and symptomatic measures towards our ultimate objective of evaluating its effects on disease burden. We will collect follow-up outcomes at one-, two- and three-months post-intervention. Public Health Significance: We will pioneer our RS-tDCS telehealth intervention for individuals seeking to discontinue cannabis, evaluated in people living with MS and applicable across the many patients with chronic brain disorders for whom cannabis may contribute to their disability. With the COVID-19 pandemic driving unprecedented rates of substance use disorders, the need for scalable, remote therapeutics that can be coupled with telehealth behavioral techniques is even more critical.

Project Narrative Cannabis is frequently used by people living with multiple sclerosis (MS), however its adverse effects are known to worsen their disease-related disability. There are currently few if any accessible interventions available to the MS patient seeking to reduce their use of cannabis, and the need for scalable, remote therapeutics to decrease distress in these individuals is more important than ever given the need for telehealth and increase of substance use disorders during the worldwide burden of COVID-19. We will target the distress component in the cycle of dependency, where cannabis use results in increased distress and in turn the increase in distress drives continued use to cope, by evaluating a novel noninvasive neuromodulation approach – remotely supervised transcranial direct current stimulation (RS-tDCS) – as tool to reduce distress and cannabis use.