The interaction of neurotransmitters and genes that control the release of dopamine is the Brain Reward Cascade (BRC). Variations within the BRC, whether genetic or epigenetic, may predispose individuals to addictive behaviors and altered pain tolerance. This discussion authored by a group of concerned scientists and clinicians examines the Genetic Addiction Risk Score (GARS), the first test to accurately predict vulnerability to pain, addiction, and other compulsive behaviors, defined as Reward Deficiency Syndrome (RDS). Innovative strategies to combat epidemic opioid, iatrogenic prescription drug abuse and death, based on the role of dopaminergic tone in pain pathways, are proposed. Sensitivity to pain may reside in the mesolimbic projection system, where genetic polymorphisms associate with a predisposition to pain vulnerability or tolerance. They provide unique therapeutic targets that could assist in the treatment of pain, and identify risk for subsequent addiction. Pharmacogenomic testing of candidate genes like CB1, mu receptors, and PENK might result in pharmacogenomic, personalized solutions, and improved clinical outcomes. Genetically identifying risk for all RDS behaviors, especially in compromised populations, may be a frontline tool to assist municipalities to provide better resource allocation.
Background/Aims:
This case series presents the novel Genetic Addiction Risk Score
(GARS®) coupled with a customized pro-dopamine regulator matched to polymorphic reward genes
having a hypodopaminergic risk.
Methods:
The proband is a female with a history of drug abuse and alcoholism. She experienced a car
accident under the influence and voluntarily entered treatment. Following an assessment, she was genotyped
using the GARS, and started a neuronutrient with a KB220 base indicated by the identified polymorphisms.
She began taking it in April 2018 and continues.
Results:
She had success in recovery from Substance Use Disorder (SUD) and improvement in socialization,
family, economic status, well-being, and attenuation of Major Depression. She tested
negative over the first two months in treatment and a recent screening. After approximately two
months, her parents also decided to take the GARS and started taking the recommended variants.
The proband’s father (a binge drinker) and mother (no SUD) both showed improvement in various
behavioral issues. Finally, the proband’s biological children were also GARS tested, showing a high
risk for SUD.
Conclusions:
This three-generation case series represents an example of the impact of genetic information
coupled with an appropriate DNA guided “Pro-Dopamine Regulator” in recovery and enhancement
of life.
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.
The aim of the present study was to evaluate the striatum's involvement in verbal awareness (semantic processing and supra-modal attention) in normals and children with attention deficit hyperactivity disorder (ADHD). Our previous finding of striatal hypoperfusion in ADHD at rest, supports our prediction that the striatum will also show reduced activation in response to tasks requiring verbal awareness. Regional cerebral blood flow (rCBF) was studied with the Xenon133 SPECT method in 12 boys with ADHD and six normal controls. The experimental controls included: (1) White Noise, (2) Passive Listening to a series of animal names, and (3) Detection of Targets ("dangerous animals") from the same series of animal names. The conditions were selected to isolate the semantic processing (Passive Listening - White Noise) and supra-modal attention components (Detection of Targets - Passive Listening of verbal awareness). ADHD children had decreased rCBF in the right striatum when compared to normals (mean difference from grand mean of each subject 8.06 ml/100 g/min vs 14.16 ml/100 g/min, p < 0.05). Factor analysis of the rCBF data revealed high factor I loadings for the frontal and striatal regions, which, in conjunction with the nature of the experimental conditions supported the inference that factor I mediated verbal awareness. Factor scores, which summarized the activity of all of the regions of interest (ROI's) on factor I, were differentially affected by the language component of the experimental tasks. Function scores were derived from factor I for the anterior cingulum and infero-frontal regions to evaluate their respective involvement in supra-modal attention and semantic processing. Function scores were also developed for the striatum, because of its central location and potential role in ADHD. The anterior cingulum was activated by supra-modal attention. The infero-frontal and the striatal regions were both activated by the language demands of the tasks. However, the striatum demonstrated reduced function scores (p < 0.05) in ADHD for all tasks. Our finding that the anterior gyrus cinguli were activated by supramodal attention and that the infero-frontal and striatal regions were activated by semantic processing supports the involvement of these ROI's in verbal awareness. Furthermore, the depressed functional contribution of the striatum to verbal awareness in ADHD children is consistent with and helps to explain their reduced cognitive control over behaviour and mental function.
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