In Search of Reward Deficiency Syndrome (RDS)-free Controls: The "Holy Grail" in Genetic Addiction Risk Testing.

BACKGROUND: The search for an accurate, gene-based test to identify heritable risk factors for Reward Deficiency Syndrome (RDS) was conducted based on hundreds of published studies about the role of dopamine in addictive behaviors, including risk for drug dependence and compulsive/impulsive behavior disorders. The term RDS was first coined by Blum's group in 1995 to identify a group of behaviors with a common neurobiological mechanism associated with a polymorphic allelic propensity for hypodopaminergia. OBJECTIVES: To outline the process used to select risk alleles of reward genes for the Genetic Addiction Risk Score (GARS) test. Consequently, to address the limitations caused by inconsistent results that occur in many case-control behavioral association studies. These limitations are perhaps due to the failure of investigators to adequately screen controls for drug and alcohol use disorder, and any of the many RDS behaviors, including nicotine dependence, obesity, pathological gambling, and internet gaming addiction. METHODS: Review of the literature related to the function of risk alleles of reward genes associated with hypodopaminergia relevant case-control association studies for the selection of alleles to be measured by the Genetic Addiction Risk Score (GARS) test. RESULTS: The prevalence of the DRD2 A1 allele in unscreened controls (33.3%), compared to "Super-Controls" [highly screened RDS controls (3.3%) in proband and family] is used to exemplify a possible solution. CONCLUSION: Unlike one gene-one disease (OGOD), RDS is polygenetic, and very complex. In addition, any RDS-related behaviors must be eliminated from the control group in order to obtain the best possible statistical analysis instead of comparing the phenotype with disease-ridden controls.

Hypodopaminergia and "Precision Behavioral Management" (PBM): It is a Generational Family Affair.

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. CONCLUSION: 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.

Death by Opioids: Are there non-addictive scientific solutions?

In the face of the current Opioid crisis in America killing close to 800,000 people since 2004, we are proposing a novel approach to assist in at least attenuating these unwanted premature deaths. While we applaud the wonderful efforts of our governmental institutes and professional societies (NIDA, NIAAA, ASAM, ABAM ) in their extraordinary efforts in combating this continued dilemma, the current approach is failing, and other alternative approaches should at least be tested. These truths present a serious ethical dilemma to scientists, clinicians and counselors in the Reward Deficiency Syndrome (RDS) treatment community. It is important to realize that the current DSM-5 does not actually accurately display the natural brain reward process. The human brain has not been designed to carve out specific drugs like opioids, alcohol, nicotine, cocaine, benzodiazepines or cannabis and process addictions such as gambling as distinct endophenotypes. This is true in spite of natural ligands for cannabinoids, endorphins, or even benzodiazepines. The most accurate endophenotype is indeed reward dysfunction (e.g hypodopaminergic or hyperdopaminergic). With this mind, we are hereby proposing that the current Medication Assisted Treatment (i.e. 'MAT') expands to needed individuals as an initial "Band-Aid" to reduce harm avoidance, with the long-term goal of prophylaxis. So, to be clear, there may be other promising modalities other than MAT such as repetitive transcranial magnetic stimulation (rTMS), exercise and even new medications with positive allosteric modulators of GABA-A receptors, as well as the highly researched Genetic Addiction Risk Score (GARS) coupled with precision KB220Z. This will induce "dopamine homeostasis" to effectively rebalance and restore healthier brain function by promoting the cross talk between various brain regions (e.g. Nucleus accumbens, cingulate gyrus, hippocampus etc.) resulting in dopamine homeostasis. Our laudable goal is to not only save lives, but to redeem joy and improve the quality of life in the recovery community through scientifically sound natural non-addicting alternatives.

The Benefits of Genetic Addiction Risk Score (GARS™) Testing in Substance Use Disorder (SUD).

Following 25 years of extensive research by many scientists worldwide, a panel of ten reward gene risk variants, called the Genetic Addiction Risk Score (GARS), has been developed. In unpublished work, when GARS was compared to the Addiction Severity Index (ASI), which has been used in many clinical settings, GARS significantly predicted the severity of both alcohol and drug dependency. In support of early testing for addiction and other RDS subtypes, parents caught up in the current demographic of 127 people, both young and old, dying daily from opiate/opioid overdose, need help. In the past, families would have never guessed that their loved ones would die or could be in real danger due to opiate addiction. Author, Bill Moyers, in Parade Magazine, reported that as he traveled around the United States, he found many children with ADHD and other spectrum disorders like Autism, and noted that many of these children had related conditions like substance abuse. He called for better ways to identify these children and treat them with approaches other than addictive pharmaceuticals. To our knowledge, GARS is the only panel of genes with established polymorphisms reflecting the Brain Reward Cascade (BRC), which has been correlated with the ASI-MV alcohol and drug risk severity score. While other studies are required to confirm and extend the GARS test to include other genes and polymorphisms that associate with an hypodopaminergic trait, these results provide clinicians with a non-invasive genetic test. Genomic testing, such as GARS, can improve clinical interactions and decision-making. Knowledge of precise polymorphic associations can help in the attenuation of guilt and denial, corroboration of family gene-o-grams; assistance in risk-severity-based decisions about appropriate therapies, including pain medications and risk for addiction; choice of the appropriate level of care placement (i.e., inpatient, outpatient, intensive outpatient, residential); determination of the length of stay in treatment; determination of genetic severity-based relapse and recovery liability and vulnerability; determination of pharmacogenetic medical monitoring for better clinical outcomes (e.g., the A1 allele of the DRD2 gene reduces the binding to opioid delta receptors in the brain, thus, reducing Naltrexone's clinical effectiveness); and supporting medical necessity for insurance scrutiny.

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

Background Addictive-like behaviors (e.g., hoarding and shopping) may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants as well as elevated stress levels. We, therefore, propose that dopamine homeostasis may be the preferred goal in combating such challenging and unwanted behaviors, when simple dopaminergic activation through potent agonists may not provide any resolution. Case presentation C.J. is a 38-year-old, single, female, living with her mother. She has a history of substance use disorder as well as attention deficit hyperactivity disorder, inattentive type. She had been stable on buprenorphine/naloxone combination and amphetamine, dextroamphetamine mixed salts for many years when unexpectedly she lost her job for oversleeping and not calling into work. KB200z (a pro-dopamine compound) was added to her regimen for complaints of low drive and motivation. After taking this nutraceutical for 4 weeks, she noticed a marked improvement in her mental status and many behaviors. She noted that her shopping and hoarding addictions had appreciably decreased. Furthermore, her lifelong history of terrifying lucid dreams was eliminated. Finally, she felt more in control; her locus of control shifted from external to more internal. Discussion The hypothesis is that C.J.'s reported, behavioral, and psychological benefits resulted from the pro-dopamine-regulating effect of KB220Z across the brain reward system. Conclusions This effect, we surmise, could be the result of a new dopamine balance, across C.J.'s brain reward system. Dopamine homeostasis is an effect of KB220Z seen in both animal and human placebo-controlled fMRI experiments.

Genetic addiction risk score (GARS) ™, a predictor of vulnerability to opioid dependence.

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.

The effects of residential dual diagnosis treatment on alcohol abuse.

This multi-center study of dual diagnosis (DD) programs involved 804 residential patients with co-occurring alcohol and mental health disorders. The Addiction Severity Index was administered at admission and at one, six, and 12 months after discharge. Repeated measures analysis showed the intoxication rate per month stabilized between months six and 12 with 68% still in remission and an 88% mean reduction from baseline (F = 519, p < .005). A comparison between patients with and without weekly relapse produced significant differences in hospitalization (odds ratio 11.3:1; 95% C.I., 5.5 to 23.2). Eight ANCOVAs used mean intoxication days per month after discharge as the outcome variable, pre-admission intoxication days per month as a covariate, and eight variables associated with relapse (e.g. depression) as factors. Patients with these factors at admission did not have significantly higher intoxication rates after discharge than patients without them. This suggests that these DD programs successfully integrated treatment of both disorders and explained their effectiveness. Co-occurring DSM IV mood disorders such as anxiety and depression as well as drug abuse involving opioids or cocaine fell between 66 and 95% at months one, six, and twelve.

Pro-Dopamine Regulator - (KB220) to Balance Brain Reward Circuitry in Reward Deficiency Syndrome (RDS).

We are faced with a worldwide opiate/opioid epidemic that is devastating. According to the Centers for Disease Control and Prevention (CDC), at least 127 people, young and old, are dying every day in America due to narcotic overdose. The Food and Drug Administration (FDA) has approved Medication-Assisted Treatments (MATs) for opiate/opioids as well as alcohol and nicotine. The mechanism of action of most MATS favors either blocking of dopaminergic function or a form of Opiate Substitution Therapy (OST). These treatment options are adequate for short-term treatment of the symptoms of addiction and harm reduction but fail long-term to deal with the cause or lead to recovery. There is a need to continue to seek better treatment options. This mini-review is the history of the development of one such treatment; a glutaminergic-dopaminergic optimization complex called KB220. Growing evidence indicates that brain reward circuitry controls drug addiction, in conjunction with "anti-reward systems" as the "anti-reward systems" can be affected by both glutaminergic and dopaminergic transmission. KB220 may likely alter the function of these regions and provide for the possible eventual balancing the brain reward system and the induction of "dopamine homeostasis." Many of these concepts have been reported elsewhere and have become an integral part of the addiction science literature. However, the concise review may encourage readership to reconsider these facts and stimulate further research focused on the impact that the induction of "dopamine homeostasis" may have on recovery and relapse prevention.

Lyme and Dopaminergic Function: Hypothesizing Reduced Reward Deficiency Symptomatology by Regulating Dopamine Transmission.

The principal vector of Lyme disease in the United States is Ixodes scapularis: black legged or deer ticks. There is increased evidence that those infected may be plagued by anxiety or depression as well. Researchers have identified transcripts coding for two putative cytosolic sulfotransferases in these ticks, which recognized phenolic monoamines as their substrates. It is hypothesized that protracted Lyme disease sequelae may be due to impairment of dopaminergic function of the brain reward circuitry. The subsequent recombinant proteins exhibited sulfotransferase function against two neurotransmitters: dopamine and octopamine. This, in itself, can reduce dopamine function leading to many Reward Deficiency Syndrome behaviors, including depression and possibly, anxiety. In fact, it was shown that activity of Ixosc Sult 1 and Sult 2 in the Ixodid tick salivary glands might contain inactivation of the salivation signal through sulfonation of either dopamine or octopamine. This infraction results in a number of clinically observed mood changes, such as anxiety and depression. In fact, there are common symptoms observed for both Parkinson and Lyme diseases. The importance of understanding the mechanistic and neurobiological effects of Lyme on the central nervous system (CNS) provides the basis for pro-dopamine regulation as a treatment. WC 195.

"Dopamine homeostasis" requires balanced polypharmacy: Issue with destructive, powerful dopamine agents to combat America's drug epidemic.

The well-researched pro-dopamine regulator KB220 and variants result in increased functional connectivity in both animal and human brains, and prolonged neuroplasticity (brain cell repair) having been observed in rodents. Moreover, in addition to increased functional connectivity, recent studies show that KB220Z increases overall brain connectivity volume, enhances neuronal dopamine firing, and eliminates lucid dreams in humans over a prolonged period. An unprecedented number of clinical studies validating this patented nutrigenomic technology in re-balancing brain chemistry and optimizing dopamine sensitivity and function have been published. On another note, it is sad that unsuspecting consumers could be deceived and endangered by false promises of knock-off marketers with look- and- sound-alike products. Products containing ingredients having potential dangers (i.e., combinations of potent D2 agonists including L-Dopa and L-Theanine) threaten the credibility and reputation of validated, authentic, and ethical products. We encourage clinicians and neuroscientists to continue to embrace the concept of "dopamine homeostasis" and search for safe, effective, validated and authentic means to achieve a lifetime of recovery, instead of reverting to anti-dopaminergic agents doomed to fail in the war against the devastating drug epidemic, or promoting powerful D2 agonists that compromise needed balance.

Improvement of long-term memory access with a pro-dopamine regulator in an elderly male: Are we targeting dopamine tone?

With aging, there is decline in both short-term and long-term memory. This effect is magnified by epigenetic insults on specific, dopamine- related genes (e.g., DRD2, DAT1) as well as by impaired or reduced mRNA transcription. In addition, long-term memory ability is positively correlated with dopamine function and there is evidence that aging is associated with a reduction in brain dopamine D2 receptors, with an acceleration seen in aging-induced dementia. As a result, the authors tested the acute effect of a Pro-Dopamine Regulator (KB220Z, liquid Nano variant) on an aspect of long-term memory performance in a 77-year-old, highly functional male, using the Animal Naming Test (ANT). An improvement in long-term memory retrieval had initially been noted during the subject's follow-up neurology exam, after he had been, for other reasons, taking KB220z. The patient had been given a number of ANTs by his primary and, later, another neurologist, from 2013 to 2016. Because the number of ANT observations was small (N = 7 with two groups) and the data uncorrelated, a non-parametric Wilcoxon-Mann-Whitney test was performed to test mean differences. After KB220z, the patient had much higher scores (p = 0.04762) on the ANT vs. when not taking it. His scores increased from the 30th percentile (pre-test) to the 76th percentile, after the first administration of KB220z and, later, to the 98th percentile, after a second administration of KB220z, six months later. The results indicate that KB220z, given acutely, increased a form of long-term memory retrieval in a highly functional, elderly male. Larger, double-blind, randomized controlled studies are encouraged.

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

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 BENEFITS OF CUSTOMIZED DNA DIRECTED NUTRITION TO BALANCE THE BRAIN REWARD CIRCUITRY AND REDUCE ADDICTIVE BEHAVIORS.

DNA Customization of nutraceutical products is here. In the truest sense, "Gene Guided Precision Nutrition™" and KB220 variants (a complex mixture of amino-acids, trace metals, and herbals) are the pioneers and standard-bearers for a state of the art DNA customization. Findings by both, Kenneth Blum, Ph.D. and Ernest Noble, Ph.D. concerning the role of genes in shaping cravings and pleasure- seeking, opened the doors to comprehension of how genetics control our actions and effect our mental and physical health. Moreover, technology that is related to KB220 variants in order to reduce or eradicate excessive cravings by influencing gene expression is a cornerstone in the pioneering of the practical applications of nutrigenomics. Continuing discoveries have been an important catalyst for the evolution, expansion, and scientific recognition of the significance of nutrigenomics and its remarkable contributions to human health. Neuro-Nutrigenomics is now a very important field of scientific investigation that offers great promise to improving the human condition. In the forefront is the development of the Genetic Addiction Risk Score (GARS™), which unlike 23andMe, has predictive value for the severity of drug and alcohol abuse as well as other non-substance related addictive behaviors. While customization of neuronutrients has not yet been commercialized, there is emerging evidence that in the future, the concept will be developed and could have a significant impact in addiction medicine.