Summary Document Research on RDS Anti-addiction Modeling: Annotated Bibliography.

Annotated bibliography of genetic addiction risk severity (GARS) publications, pro-dopamine regulation in nutraceuticals (KB220 nutraceutical variants), and policy documents. Further research is required to encourage the field to consider "Reward Deficiency Syndrome (RDS) Anti-addiction Modeling" which involves early risk identification by means of genetic assessment similar to GARS, followed by induction of dopamine homeostasis by means of genetically guided pro-dopamine regulation similar to KB220. These results suggest that genetically based treatments may be a missing piece in the treatment of substance use disorder (SUD).

Addressing cortex dysregulation in youth through brain health check coaching and prophylactic brain development.

The Carter Center has estimated that the addiction crisis in the United States (US), if continues to worsen at the same rate, may cost the country approximately 16 trillion dollars by 2030. In recent years, the well-being of youth has been compromised by not only the coronavirus disease 2019 pandemic but also the alarming global opioid crisis, particularly in the US. Each year, deadly opioid drugs claim hundreds of thousands of lives, contributing to an ever-rising death toll. In addition, maternal usage of opioids and other drugs during pregnancy could compromise the neurodevelopment of children. A high rate of DNA polymorphic antecedents compounds the occurrence of epigenetic insults involving methylation of specific essential genes related to normal brain function. These genetic antecedent insults affect healthy DNA and mRNA transcription, leading to a loss of proteins required for normal brain development and function in youth. Myelination in the frontal cortex, a process known to extend until the late 20s, delays the development of proficient executive function and decision-making abilities. Understanding this delay in brain development, along with the presence of potential high-risk antecedent polymorphic variants or alleles and generational epigenetics, provides a clear rationale for embracing the Brain Research Commission's suggestion to mimic fitness programs with an adaptable brain health check (BHC). Implementing the BHC within the educational systems in the US and other countries could serve as an effective initiative for proactive therapies aimed at reducing juvenile mental health problems and eventually criminal activities, addiction, and other behaviors associated with reward deficiency syndrome.

EPIC Spinal Procedure with Sound Wave Technology Induces Biomechanical Alignment Putatively Influencing Pain Response.

Spinal biomechanical alignment is now able to be altered through the use of unique sound wave technology. This methodological commentary will correlate recent studies demonstrating the ability of sound waves to carry mass, how the EPIC technique spinal procedure uses a sound wave impulse to create measurable changes in spinal alignment, and the clinical safety and efficacy of this approach. The EPIC technique is a direct genealogical descendant of the technique originally developed by the founding family of chiropractic. With sound wave therapies currently being used to break up kidney stones, called lithotripsy, in physical therapy for the treatment of soft tissue injuries, in the treatment of prostate cancer, and in the treatment of Alzheimer's disease, it is possible that the use of sound wave therapies may enter into the realm of altering joint biomechanics. Through a neurovascular examination, the EPIC technique spinal procedure can ascertain the presence of craniocervical subluxation, followed by acquiring multi-dimensional radiographic images for structural analysis. Currently using digital radiographic analysis, the EPIC technique acquires an epigenetic profile of structural asymmetries as well as a multi-directional biomechanical malposition profile of the spine, combining both profiles to ascertain the exact degrees for realignment. EPIC clinics have successfully utilized EPIC on over 20,000 cases. Comparison of pre-treatment biomechanical lateral displacement of the C1 vertebra around the Z-axis measured on digital radiographs, and post-treatment biomechanical lateral displacement of the C1 vertebra measured on digital radiographs immediately following the procedure, demonstrated an average 52% reduction in lateral biomechanical displacement around the Z-axis in a select group of over 2,000 cases. While more research is required, we are encouraged by these preliminary results. WC 265.

Futuristic Thinking about Engineering "Geneospirituality" to Help Prevent Relapse of Reward Deficiency Syndrome (RDS) Behaviors.

It is with a saddened heart that we are dedicating this article to the loving memory of our dear departed friend and associate B. William Downs. Bill was well known in the nutritional space worldwide for his major contributions to the health and welfare of millions around the globe. The founder of Victory Nutrition International (VNI) in conjunction with Kim Downs, as well as so many contributions to scientific literature, to those that knew him personally will forever be touched. Bill was a highly spirited human with a never ending love for caring and helping so many individuals. To know Bill is to walk in the face of a music lover playing drums, trained as a martial artist, and riding through the winds of a Beamer driven by an iconic man driven to victory. Our hearts may be saddened but Bills spirit to those that know him will be forever. In this article we discuss and review some potential futuristic concepts and technological advancements in terms of geneospirituality engineering to help prevent relapse and or even protect against an unwanted predisposition to RDS behaviors. Futuristic development may contribute to an attenuation of both DNA antecedents as well as epigenetic reward system insults leading to unwanted substance and non-substance addictive behaviors.

The Future is Now for Precision Genomic Addiction Medicine as a Frontline Modality for Inducing "Dopamine Homeostasis" in Reward Deficiency Syndrome (RDS).

INTRODUCTION: In this genomic era of addiction medicine, ideal treatment planning begins with genetic screening to determine neurogenetic antecedents of the Reward Deficiency Syndrome (RDS) phenotype. Patients suffering from endotype addictions, both substance and behavioral, and other mental health/comorbid disorders that share the neurobiological commonality of dopamine dysfunction, are ideal candidates for RDS solutions that facilitate dopamine homeostasis, addressing the cause, rather than symptoms. OBJECTIVE: Our goal is to promote the interplay of molecular biology and recovery as well as provide evidence linked to RDS and its scientific basis to primary care physicians and others. METHODS: This was an observational case study with a retrospective chart review in which an RDS treatment plan that utilized Genetic Addiction Risk Severity (GARS) analysis to evaluate neurogenetic challenges was used in order to develop appropriate short- and long-term pharmaceutical and nutraceutical interventions. RESULTS: A Substance Use Disorder (SUD) treatment-resistant patient was successfully treated utilizing the GARS test and RDS science. CONCLUSION: The RDS Solution Focused Brief Therapy (RDS-SFBT) and the RDS Severity of Symptoms Scale (SOS) may provide clinicians with a useful tool for establishing neurological balance and helping patients to achieve self-efficacy, self-actualization, and prosperity.

Future Newborns with Opioid-Induced Neonatal Abstinence Syndrome (NAS) Could Be Assessed with the Genetic Addiction Risk Severity (GARS) Test and Potentially Treated Using Precision Amino-Acid Enkephalinase Inhibition Therapy (KB220) as a Frontline Modality Instead of Potent Opioids.

In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of primarily opioid-induced NAS. Newborns of individuals who use illicit and licit substances during pregnancy are at risk for withdrawal, also known as NAS. In the US, the reported prevalence of NAS has increased from 4.0 per 1000 hospital births in 2010 to 7.3 per 1000 hospital births in 2017, which is an 82% increase. The management of NAS is varied and involves a combination of nonpharmacologic and pharmacologic therapy. The preferred first-line pharmacological treatment for NAS is opioid therapy, specifically morphine, and the goal is the short-term improvement in NAS symptomatology. Nonpharmacological therapies are individualized and typically focus on general care measures, the newborn-parent/caregiver relationship, the environment, and feeding. When used appropriately, nonpharmacologic therapies can help newborns with NAS avoid or reduce the amount of pharmacologic therapy required and the length of hospitalization. In addition, genetic polymorphisms of the catechol-o-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes appear to affect the length of stay and the need for pharmacotherapy in newborns with prenatal opioid exposure. Therefore, based on this extensive literature and additional research, this team of coauthors suggests that, in the future, in addition to the current nonpharmacological therapies, patients with opioid-induced NAS should undergo genetic assessment (i.e., the genetic addiction risk severity (GARS) test), which can subsequently be used to guide DNA-directed precision amino-acid enkephalinase inhibition (KB220) therapy as a frontline modality instead of potent opioids.

Hypothesizing in the Face of the Opioid Crisis Coupling Genetic Addiction Risk Severity (GARS) Testing with Electrotherapeutic Nonopioid Modalities Such as H-Wave Could Attenuate Both Pain and Hedonic Addictive Behaviors.

In the United States, amid the opioid overdose epidemic, nonaddicting/nonpharmacological proven strategies are available to treat pain and manage chronic pain effectively without opioids. Evidence supporting the long-term use of opioids for pain is lacking, as is the will to alter the drug-embracing culture in American chronic pain management. Some pain clinicians seem to prefer classical analgesic agents that promote unwanted tolerance to analgesics and subsequent biological induction of the "addictive brain". Reward genes play a vital part in modulation of nociception and adaptations in the dopaminergic circuitry. They may affect various sensory and affective components of the chronic pain syndromes. The Genetic Addiction Risk Severity (GARS) test coupled with the H-Wave at entry in pain clinics could attenuate pain and help prevent addiction. The GARS test results identify high-risk for both drug and alcohol, and H-Wave can be initiated to treat pain instead of opioids. The utilization of H-Wave to aid in pain reduction and mitigation of hedonic addictive behaviors is recommended, notwithstanding required randomized control studies. This frontline approach would reduce the possibility of long-term neurobiological deficits and fatalities associated with potent opioid analgesics.

Proposing FDA consideration for the treatment and prophylaxis of opioid and psychostimulant abuse to incorporate the induction of DNA guided dopamine homeostasis: Anti-reward deficiency restoration solution (ARDS).

Background: In face of an American opioid/psychostimulant crisis with overdose fatalities, due, in part, to the COVOD 19 pandemic, we are proposing a paradigm shift in response. Currently, The FDA has approved pharmaceuticals for the treatment of opioids, alcohol, and nicotine but not for psychostimulants or even cannabis. Proposition: To respond to the deadly overdose issue globally, we are proposing that the FDA embrace, for the treatment and prophylaxis of opioid and psychostimulant abuse, induction of DNA-guided, dopamine homeostasis. We refer to this novel therapeutic target as the Anti-Reward Deficiency Restoration Solution (ARDS). Expert opinion: This futuristic proposal regarding the FDA will provide important information that may ultimately lead to significant improvement in the recovery of individuals with opioid/psychostimulant and polydrug abuse issues, especially, those with genetically-induced dopamine deficiency. Conclusion: With large populations supporting these initial results, and possibly even additional candidate genes and single nucleotide polymorphisms, the neuroscience and neurological community may eventually have the clinical ability to classify addiction severity, according to genotype and possession of risk alleles. A promising goal is the identification of high risk vulnerability, along with the provision of a safe, non-addicting ARDS natural nutrigenomic, involving a therapeutic model that potentially up-regulates instead of down-regulates dopaminergic receptors, preferably, the D2 subtype, is one laudable goal.

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.

Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z.

Dopaminergic reward dysfunction in addictive behaviors is well supported in the literature. There is evidence that alterations in synchronous neural activity between brain regions subserving reward and various cognitive functions may significantly contribute to substance-related disorders. This study presents the first evidence showing that a pro-dopaminergic nutraceutical (KB220Z) significantly enhances, above placebo, functional connectivity between reward and cognitive brain areas in the rat. These include the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and dopaminergic functionality were found across the brain reward circuitry. Increases in functional connectivity were specific to these regions and were not broadly distributed across the brain. While these initial findings have been observed in drug naïve rodents, this robust, yet selective response implies clinical relevance for addicted individuals at risk for relapse, who show reductions in functional connectivity after protracted withdrawal. Future studies will evaluate KB220Z in animal models of addiction.

Hypothesizing Las Vegas and Sutherland Springs Mass Shooters Suffer from Reward Deficiency Syndrome: "Born Bad".

The slaughters in Las Vegas and Sutherland Springs demand explanation, in the face of the ineffable. An understanding of the shooters' motives could restore our trust in our mutually cooperative existence. In this short communication we provide post-hoc rationale of both Stephen Paddock (Las Vegas mass shooting) and Devin Kelley (Southerland Springs mass shooting) and hypothesize that these shooters had genetically induced "Reward Deficiency Syndrome" (RDS) and a hypodopaminergia trait/state. In this particular case we are in pursuit of trying to obtain postmortem samples of mass shooters for subsequent epigenetic and neurogenetic analyses. It is our contention that early genetic identification of RDS and its pathological behaviors including hyper - sexuality, violence, a love for guns, even in children, could be a giant step forward in potentially saving lives.

"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.

Pilot clinical observations between food and drug seeking derived from fifty cases attending an eating disorder clinic.

Background The reward deficiency syndrome hypothesis posits that genes are responsible for reward dependence and related behaviors. There is evidence that both bulimia and anorexia nervosa, especially in women, have been linked to a lifetime history of substance use disorder (SUD). There are difficulties in accepting food as an addiction similar to drugs; however, increasingly neuroimaging studies favor such an assertion. Case presentations We are reporting the evidence of comorbidity of eating disorders with SUD found within these case presentations. We show 50 case reports derived from two independent treatment centers in Florida that suggest the commonality between food and drug addictions. In an attempt to provide data from this cohort, many participants did not adequately respond to our questionnaire. Discussion We propose that dopamine agonist therapy may be of common benefit. Failure in the past may reside in too powerful D2 agonist activity leading to D2 receptor downregulation, while the new methodology may cause a reduction of "dopamine resistance" by inducing "dopamine homeostasis." While this is not a definitive study, it does provide some additional clinical evidence that these two addictions are not mutually exclusive. Conclusion Certainly, it is our position that there is an overlap between food- and drug-seeking behavior. We propose that the studies focused on an effort to produce natural activation of dopaminergic reward circuitry as a type of common therapy may certainly be reasonable. Additional research is warranted.

Hypothesizing that a Pro-Dopaminergic Regulator (KB220z™ Liquid Variant) can Induce "Dopamine Homeostasis" and Provide Adjunctive Detoxification Benefits in Opiate/Opioid Dependence.

In order to explore the initiation of detoxification of addictive patients to opiates/opioids (along with some other anti-withdrawal agents), we developed a protocol to be utilized in treatment centers particularly with heavily dependent opiate/opioid subjects. Out of 17 subjects, only three received Buprenorphine/Naloxone (Bup/nx) along with KB220Z. In this pilot, we first used a dose of KB220Z of 2 oz twice daily before meals along with clonidine and benzodiazepines and other anti-nausea and sleep aids including Gabapentin. The dose of KB220Z was maintained for 6 days in five individuals. In a second scenario, we utilized a higher dose of 4 oz every 6 hours, over a 6-day period. The higher dose was employed in another 12 patients. It is noteworthy that only 3 people have relapsed utilizing these two protocols during the first two weeks of the study, allowing for the remaining 82% to be maintained on KB220Z. The patients have been maintained without any additional Bup/nx for a minimum of 120 days and in one subject, 214 days. We are in the process of testing this hypothesis in multiple treatment centers across the United Sates utilizing data from the Clinical opiate Withdrawal Scale (COWS) pre and post KB220Z. We are in the process of testing this hypothesis in multiple treatment centers across the United Sates. While this does not constitute an acceptable controlled experiment, it does provide some preliminary evidence that agrees with an earlier study. Moreover, because of the utilization of standard detoxifying agents in this detoxification protocol, we cannot make any inference to KB220Z's effects. However, out of 17 subjects, only three required Bup/nx suggesting an interesting finding. If further confirmed in larger studies, the utilization for opiate/opioid detoxification may provide a novel way to eliminate the need for addictive opioids during withdrawal and detoxification. This paradigm shift may translate to a reduction in utilizing powerful and addictive opioids like buprenorphine and methadone (especially in these patients at high genetic risk for addiction) as not only detoxifying agents, but also maintenance drugs. While extensive research is required, this pilot paves the way for future investigations that could assist in the reduction of addictive opiate/opioid use and mortalities amongst both the young and old in America.

The Molecular Neurobiology of Twelve Steps Program & Fellowship: Connecting the Dots for Recovery.

There are some who suggest that alcoholism and drug abuse are not diseases at all and that they are not consequences of a brain disorder as espoused recently by the American Society of Addiction Medicine (ASAM). Some would argue that addicts can quit on their own and moderate their alcohol and drug intake. When they present to a treatment program or enter the 12 Step Program & Fellowship, many addicts finally achieve complete abstinence. However, when controlled drinking fails, there may be successful alternatives that fit particular groups of individuals. In this expert opinion, we attempt to identify personal differences in recovery, by clarifying the molecular neurobiological basis of each step of the 12 Step Program. We explore the impact that the molecular neurobiological basis of the 12 steps can have on Reward Deficiency Syndrome (RDS) despite addiction risk gene polymorphisms. This exploration has already been accomplished in part by Blum and others in a 2013 Springer Neuroscience Brief. The purpose of this expert opinion is to briefly, outline the molecular neurobiological and genetic links, especially as they relate to the role of epigenetic changes that are possible in individuals who regularly attend AA meetings. It begs the question as to whether "12 steps programs and fellowship" does induce neuroplasticity and continued dopamine D2 receptor proliferation despite carrying hypodopaminergic type polymorphisms such as DRD2 A1 allele. "Like-minded" doctors of ASAM are cognizant that patients in treatment without the "psycho-social-spiritual trio," may not be obtaining the important benefits afforded by adopting 12-step doctrines. Are we better off with coupling medical assisted treatment (MAT) that favors combining dopamine agonist modalities (DAM) as possible histone-deacetylase activators with the 12 steps followed by a program that embraces either one or the other? While there are many unanswered questions, at least we have reached a time when "science meets recovery," and in doing so, can further redeem joy in recovery.

NIDA-Drug Addiction Treatment Outcome Study (DATOS) Relapse as a Function of Spirituality/Religiosity.

BACKGROUND: The connection between religion/spirituality and deviance, like substance abuse, was first made by Durkheim who defined socially expected behaviors as norms. He explained that deviance is due in large part to their absence (called anomie), and concluded that spirituality lowers deviance by preserving norms and social bonds. Impairments in brain reward circuitry, as observed in Reward Deficiency Syndrome (RDS), may also result in deviance and as such we wondered if stronger belief in spirituality practice and religious belief could lower relapse from drugs of abuse. METHODS: The NIDA Drug Addiction Treatment Outcome Study data set was used to examine post hoc relapse rates among 2,947 clients who were interviewed at 12 months after intake broken down by five spirituality measures. RESULTS: Our main findings strongly indicate, that those with low spirituality have higher relapse rates and those with high spirituality have higher remission rates with crack use being the sole exception. We found significant differences in terms of cocaine, heroin, alcohol, and marijuana relapse as a function of strength of religious beliefs (x2 = 15.18, p = 0.028; logistic regression = 10.65, p = 0.006); frequency of attending religious services (x2 = 40.78, p < 0.0005; logistic regression = 30.45, p < 0.0005); frequency of reading religious books (x2 = 27.190, p < 0.0005; logistic regression = 17.31, p < 0.0005); frequency of watching religious programs (x2 = 19.02, p = 0.002; logistic regression = ns); and frequency of meditation/prayer (x2 = 11.33, p = 0.045; logistic regression = 9.650, p = 0.002). Across the five measures of spirituality, the spiritual participants reported between 7% and 21% less alcohol, cocaine, heroin, and marijuana use than the non-spiritual subjects. However, the crack users who reported that religion was not important reported significantly less crack use than the spiritual participants. The strongest association between remission and spirituality involves attending religious services weekly, the one marker of the five that involves the highest social interaction/social bonding consistent with Durkheim's social bond theory. CONCLUSIONS: Stronger spiritual/religious beliefs and practices are directly associated with remission from abused drugs except crack. Much like the value of having a sponsor, for clients who abuse drugs, regular spiritual practice, particularly weekly attendance at the religious services of their choice is associated with significantly higher remission. These results demonstrate the clinically significant role of spirituality and the social bonds it creates in drug treatment programs.

Drug abuse relapse rates linked to level of education: can we repair hypodopaminergic-induced cognitive decline with nutrient therapy?

It is well known that athletes and other individuals who have suffered painful injuries are at increased risk for all reward deficiency syndrome (RDS) behaviors, including substance use disorder (SUD). Comparing patient demographics and relapse rates in chemical dependence programs is pertinent because demographics may affect outcomes. Increased risk for relapse and lower academic achievement were found to have a significant association in recent outcome data from a holistic treatment center (HTC) located in North Miami Beach, FL. Relapse outcomes from the Drug Addiction Treatment Outcome Study (DATOS; n = 1738) and HTC (n = 224) were compared for a 12-month period. Post-discharge relapse was reported by 26% of HTC patients and 58% of patients in DATOS. When broken out by education level-less than high school, high school diploma, college degree, and graduate degree-HTC patient relapse was 50%, 36%, 33%, and 16%, respectively, and demonstrated an inverse linear association (F = 5.702; P = 0.017). Looking at DATOS patient relapse rates broken down by educational grades/years completed, patients who attended school between 7th grade and 4 years of college also demonstrated an inverse linear association (F = 5.563; P = 0.018). Additionally, the lowest performers, patients who reported their academic performance as "not so good," had the highest relapse (F = 4.226; P = 0.04). Albeit certain limitations, compared with DATOS patients, HTC patients produced significantly larger net differences in relapse rates (X 2 = 84.09; P = 0.0001), suggesting that other variables, such as the treatment model may also affect patient relapse. Our results implicate the use of vitamin and mineral supplements coupled with a well-researched natural dopamine agonist nutrient therapy; both have been shown to improve cognition and behavior, and thus academic achievement. That relapse is highest among addicts who have less education and who report lower grades is a factor that can be useful when considering treatment type and controlled for when comparing treatment outcomes.