Pharmacotherapeutics for substance-use disorders: a focus on dopaminergic medications

Abstract

Introduction Illicit substance-use is a substantial public health concern, contributing over $150 billion in costs annually to Americans. A complex disease, a substance-use disorder affects neural circuits involved in reinforcement, motivation, learning and memory, and inhibitory control. Areas covered The modulatory influence of dopamine in mesocorticolimbic circuits contributes to encoding the primary reinforcing effects of substances and numerous studies suggest that aberrant signaling within these circuits contributes to the development of a substance-use disorder in some individuals. Decades of research focused on the clinical development of medications that directly target dopamine receptors has led to recent studies of agonist-like dopaminergic treatments for stimulant-use disorders and, more recently, cannabis-use disorder. Human studies evaluating the efficacy of dopaminergic agonist-like medications to reduce reinforcing effects and substance-use provide some insight into the design of future pharmacotherapy trials. A search of PubMed using specific brain regions, medications, and/or the terms ‘dopamine’, ‘cognition’, ‘reinforcement’, ‘cocaine’, ‘methamphetamine’, ‘amphetamine’, ‘cannabis’, ‘treatment/pharmacotherapy’, ‘addiction/abuse/dependence’ identified articles relevant to this review. Expert opinion Conceptualization of substance-use disorders and their treatment continues to evolve. Current efforts increasingly focus on a strategy fostering combination pharmacotherapies that target multiple neurotransmitter systems.

Assessment of safety, cardiovascular and subjective effects after intravenous cocaine and lofexidine

“…Cocaine is a potent inhibitor of monoamine transporters, including DA, serotonin, and NE transporters (Fleckenstein et al 2000; Miller et al 2001). Cocaine binds at the DA transporter and inhibits neurotransmitter reuptake, leading to a build-up of extracellular DA levels and potentiation of mesolimbocortical pathways (Haile et al 2012b; Verrico et al 2013). The distribution half-life of cocaine from an IV dose is about 10 min and the elimination T-½ of cocaine is ~1 hour (50–80 min).…”

“…A variety of neuropharmacological strategies and targets are being pursued as treatments for cocaine addiction. Some of these strategies include blocking cocaine’s positive subjective effects, reducing cocaine craving, treating underlying co-morbid conditions that may predispose individuals to developing dependence, and stress reduction to prevent relapse (Haile & Kosten 2013; Haile et al 2012b; Verrico et al 2013). …”

The Clinical Efficacy of Mindfulness-Based Treatments for Alcohol and Drugs Use Disorders: A Meta-Analytic Review of Randomized and Nonrandomized Controlled Trials

“…Numerous studies also confirmed how pharmacotherapy might be beneficial in DUDs treatment (for overviews see: [13][14][15]). Furthermore, a variety of psychological and behavioral therapies also demonstrated to be effective (e.g., cognitive-behavioral therapy [CBT], motivational enhancement therapy, 12-step facilitation therapy [16][17][18][19]).…”

The Role of Guanfacine as a Therapeutic Agent to Address Stress-Related Pathophysiology in Cocaine-Dependent Individuals

“…As many of the subjective and reinforcing effects of cocaine have traditionally been attributed to dopaminergic deficiencies within the mesocorticolimbic pathways (Koob, 2003; Volkow, Fowler, Wang, & Goldstein, 2002), potentiating dopamine transmission via “agonist therapy” has provided an important therapeutic target for reducing withdrawal symptoms and preventing relapse (Verrico, Haile, Newton, Kosten, & De La Garza, 2013). However, many of these candidate medications have been limited due to their high abuse liability and high prevalence of side effects (Diana, 2011; Thanos et al, 2004).…”