Hypothesizing That Neuropharmacological and Neuroimaging Studies of Glutaminergic-Dopaminergic Optimization Complex (KB220Z) Are Associated With “Dopamine Homeostasis” in Reward Deficiency Syndrome (RDS)

Abstract

Background There is need for better treatments of addictive behaviors, both substance and non-substance related, termed “Reward Deficiency Syndrome” (RDS). While the FDA has approved pharmaceuticals under the umbrella term Medication Assisted Treatment (MAT), these drugs are not optimal. Objectives It is our contention that these drugs work well in the short-term by blocking dopamine function leading to psychological extinction. However, use of buprenorphine/Naloxone over a long period of time results in unwanted addiction liability, reduced emotional affect, and mood changes including suicidal ideation. Methods We are thus proposing a paradigm shift in addiction treatment, with the long-term goal of achieving “Dopamine Homeostasis.” While this may be a laudable goal, it is very difficult to achieve. Nevertheless, this commentary briefly reviews past history of developing and subsequently, utilizing a glutaminergic-dopaminergic optimization complex [Kb220Z] shown to be beneficial in at least 20 human clinical trials and in a number of published and unpublished studies. Results It is our opinion that, while additional required studies could confirm these findings to date, the cited studies are indicative of achieving enhanced resting state functional connectivity, connectivity volume, and possibly, neuroplasticity. Conclusions/Importance We are proposing a Reward Deficiency Solution System (RDSS) that includes: Genetic Addiction Risk Score (GARS); Comprehensive Analysis of Reported Drugs (CARD); and a glutaminergic-dopaminergic optimization complex (Kb220Z). Continued investigation of this novel strategy may lead to a better-targeted approach in the long-term, causing dopamine regulation by balancing the glutaminergic-dopaminergic pathways. This may potentially change the landscape of treating all addictions leading us to the promised land.

Physical Exercise Interventions for Drug Addictive Disorder

“…Dopamine subtype 2 receptor (D2DR) knockdown mice fail to gain weight or exhibit elevated appetitive motivation in comparison with the wild-type mice within standard environments yet in enriched environments incorporating voluntary exercise facilities, these D2DR knockdown mice expressed markedly lower activity with a rapid increase in obesity compared with the wild-type mice without being receptive of the protective benefit from exercise contingencies [ 14 ]. Thus, an underlying mechanism for conceptualizing and treating addictive problems ought to be the reinstatement of a “Dopamine Homeostasis” [ 15 ].…”

Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD)

“…It is the goal through this novel model that by using PBM the addiction field will have a synergistic tool along with MAT or even alone, to overcome dopamine dysregulation either surfeit (adolescents) or deficit (adults) by the induction of “ dopamine homeostasis” to help attenuate SUD by enabling early intervention through genetic testing [ 23 , 24 ].…”

“…To date there have been 42 published studies on KB220 related to many RDS behaviors [22]. There is evidence derived from animal and human studies using BOLD neuroimaging and behavioral methodologies that support homeostatic activation of brain dopamine in the reward circuitry by KB220 variants, as well as anti-substance seeking and modification of RDS behaviors [23][24][25][26][27][28]. RDS encompasses behaviors like PTSD, ADHD, over-eating, shopping, hoarding and related RDS cognitive insults.…”

Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD

“…Regarding both hoarding and shopping issues, the elimination of these unwanted behaviors in the patient is at the core of the mechanism of action of KB220Z. Previous work adequately showed not only selective DA activation across the brain reward circuitry ( Febo et al., 2017 ), but also evidence for DA homeostasis in protracted heroin dependence ( Blum, Febo, et al., 2017 ; Blum, Liu, et al., 2015 ).…”