Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist Therapy as a Paradigm Shift: Dopamine for Dinner?

Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist Therapy as a Paradigm Shift: Dopamine for Dinner? Kenneth Blum 0 1 2 3 4 5 Marcelo Febo 0 1 2 3 4 5 Panayotis K. Thanos 0 1 2 3 4 5 David Baron 0 1 2 3 4 5 James Fratantonio 0 1 2 3 4 5 Mark Gold 0 1 2 3 4 5 0 M. Gold Department of Research, Rivermernd Health , Atlanta, GA , USA 1 D. Baron Keck School of Medicine, University of Southern California , Los Angeles, CA , USA 2 D. Baron Department of Psychiatry, Keck School of Medicine, University of Southern California , Los Angeles, CA , USA 3 P. K. Thanos Behavior Neuropharmacology and Neuroimaging Laboratory, Department of Psychology, SUNY at Stony Brook , Stony Brook, NY , USA 4 K. Blum Department of Addiction Research and Therapy, Malibu Beach Recovery Center , Malibu, CA , USA 5 K. Blum Human Integrated Services Unit, Center for Clinical and Translational Science, Department of Psychiatry, College of Medicine, University of Vermont , Burlington, VT , USA Everyday, there are several millions of people that are increasingly unable to combat their frustrating and even fatal romance with getting high and/or experiencing Bnormal^ feelings of well-being. In the USA, the FDA has approved pharmaceuticals for drug and alcohol abuse: tobacco and nicotine replacement therapy. The National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) remarkably continue to provide an increasing understanding of the intricate functions of brain reward circuitry through sophisticated neuroimaging and molecular genetic applied technology. Similar work is intensely investigated on a worldwide basis with enhanced clarity and increased interaction between not only individual scientists but across many disciplines. However, while it is universally agreed that dopamine is a major neurotransmitter in terms of reward dependence, there remains controversy regarding how to modulate its role clinically to treat and prevent relapse for both substance and non-substance-related addictive behaviors. While the existing FDA-approved medications promote blocking dopamine, we argue that a more prudent paradigm shift should be biphasic-short-term blockade and long-term upregulation, enhancing functional connectivity of brain reward circuits. Dopamine; Reward deficiency syndrome (RDS); Agonistic therapy; Dopamine societies; Genetics and epigenetics - Mille viae ducunt homines per saecula Romam (A thousand roads lead men forever to Rome) in Liber Parabolarum, 591 (1175), by Alain de Lille. Scientific explorations from around the globe agree that substance and non-substance-seeking behaviors are considered an endemic societal problem affecting multimillions. Certainly, we have come a long way since Bill Wilson and Dr. Bob Smith began their crusade in 1933 embracing the BCambridge^ theories and doctrines, resulting in the most powerful anti-alcohol/drug program and fellowship in the worldAlcoholics/Narcotic Anonymous. Many years after Jelnicks famous article in 1956 providing the medical profession with the Bconcept of alcoholism as a disease,^ the American Society of Addiction Medicine (ASAM) espoused a new definition of addiction indicating that BAddiction is a primary, chronic disease involving brain reward, motivation, memory and related circuitry^; it can lead to relapse, progressive development, and the potential for fatality if not treated. While pathological use of alcohol and, more recently, psychoactive substances has been accepted as an addictive disease, developing brain science has set the stage for inclusion of the process addictions, including food, sex, shopping, and gambling problems, in a broader definition of addiction as set forth by the American Society of Addiction Medicine in 2011 [1]. To carry out this review, we searched a number of important databases including the following: filtered resources Cochrane Systematic Reviews, DARE, PubMed Central Clinical Queries, National Guideline Clearinghouse; unfiltered resourcesPsychINFO, ACP PIER, PsychSage, PubMed/MEDLINE. The major search terms included the following: dopamine agonist therapy for addiction, dopamine agonist therapy for reward dependence, dopamine antagonistic therapy for addiction, dopamine antagonistic therapy for reward dependence. Our results produced the following: dopamine agonistic therapy for addictionCochrane Systematic Reviews 0, DARE 0, PubMed Central Clinical Queries 9, National Guideline Clearinghouse 0, PsychINFO 0, ACP PIER 83, PsychSage 15, PubMed/MEDLINE 501; dopamine agonist for addictionCochrane Systematic Reviews 3, DARE 3, PubMed Central Clinical Queries 10, National Guideline Clearinghouse 0, ACP PIER 0, PsychSage 15, PubMed/MEDLINE 13; dopamine agonistic therapy for reward dependenceCochrane Systematic Reviews 0, DARE 0, PubMed Central Clinical Queries 1, National Guideline Clearinghouse 0, PsychINFO 0, ACP PIER 0, PsychSage 0, PubMed/MEDLINE 62; dopamine agonist for reward dependenceCochrane Systematic Reviews 0, DARE 0, PubMed Central Clinical Queries 337, National Guideline Clearinghouse 0, PsychINFO 1, ACP PIER 0, PsychSage 0, PubMed/MEDLINE 120 (see Fig. 1); dopamine antagonistic therapy for addictionCochrane Systematic Reviews 0, DARE 0, PubMed Central Clinical Queries 0, National Guideline Clearinghouse 0, PsychINFO 0, ACP PIER 0, PsychSage 0, PubMed/MEDLINE 633. Clearly, we utilized a combination of PubMed Central Clinical Queries and PubMed/MEDLINE for our reliable review search as well as author searches based on personal knowledge of the field. According to Belcher et al., drug addiction is characterized by a compulsive drive to take drugs despite serious negative consequences and is a disorder that involves complex interactions between genetic and environmental variables [3]. For example, undoubtedly, heroin addiction is a complex phenomenon of the brain involving both affective and cognitive processes [4]. It has been found that in heroin-dependent individuals, there is increased white matter intensity in the frontal area and decreased gray matter density in the bilateral prefrontal cortices and in the temporal regions compared to healthy subjects [5]. It was also found that there is a high accuracy in the activation pattern differences between heroin-dependent subjects and healthy individuals during resting-state brain activities. These differences of activation patterns included orbitofrontal cortex (OFC), hippocampal/parahippocampal region, amygdala, caudate, putamen, as well as the insula and thalamus [6]. Moreover, similar effects were found for alcohol as well. Specifically, Luhar et al. [7] compared non-smoking non-alcoholicsalcoholics who smoke had volumetric abnormalities in pre- and paracentral frontal cortical areas and rostral middle frontal white matter, parahippocampal and temporal pole regions, the amygdala, the pallidum, the ventral diencephalic region, and the lateral ventricle. The comorbid group (...truncated)