Joan Borsten's scientific contributions

The issue of insomnia is a global phenomenon which requires additional in-depth research. Insomnia especially in alcohol-dependent patients, for example, may lead to suicide. It is noteworthy that childhood sleep problems predict the onset of drinking in boys. We now know that while there are multi-faceted reasons for sleep problems and disturbances (e.g. sleep drive homeostasis, circadian rhythm physiology, and genetic influences), the scientific community has not been able to deliver an appropriate solution. Some benefit has been noted with cognitive behavioral therapy, but it has minimal effects in patients relapsing from drugs especially alcohol, cocaine and opiates. While there are a number of pharmaceutical drugs developed to treat insomnia, most have associated side effects and even addiction liability. We do know that benzodiazepines hijack the midbrain dopamine system leading to addiction. Finally, it has been proposed that dopamine D2 receptors are involved in rapid eye movement sleep, suggesting as proposed herein that dopaminergic activation is a worthwhile mechanism to explore in the future. The concepts presented herein on potential nutrigenomic therapy warrants further in-depth analysis. In this regard we hypothesize based on both literature review and empirical data that a putative dopaminergic, melatonin, benzodiazepine reward circuitry receptor(s) activator provides sleep induction benefits.

The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid dependence. It is well known that as well as the side effects reported for chronic opioid therapy, genetically predisposed individuals are at risk for opioid dependence. We propose the use of the Genetic Addiction Risk Score (GARS) assessment to identify patients early in treatment who should avoid narcotic pain medications. Primarily, this review will be an exploration of the mechanisms of action of an electrotherapeutic alternative to narcotic treatment that can be used to augment tissue healing and reduce the pain associated with human injuries and neuropathies. This particular electrotherapeutic device was developed at the Electronic Waveform Laboratory in Huntington Beach, California and is called the H-Wave® device. The primary effect of the H-Wave®device is stimulation (HWDS) of small diameter fibers of “red-slow-twitch” skeletal muscle. Mechanisms of action of HWDS have been investigated in both animal and human studies. They include edema reduction, induction of nitric oxide dependent augmented microcirculation and angiogenesis, small muscle contraction that eliminates transcapillary fluid shifts, reducing the painful effects of tetanizing fatigue and gradual loading of healing injured muscle tissue that helps repair and remodeling. A recent metaanalysis found a moderate-to-strong-positive effect of the HWDS in providing pain relief, reducing the requirement for pain medication, with the most robust effect being increased functionality. We are proposing that GARS can be used to identify those at risk of developing opioid dependence and that the need for opioid analgesia can be reduced by use of this electro therapeutic alternative to opioid analgesia in the treatment of pain and injuries.

A GREAT ARTICLE FOR ALL TO UNDERSTAND RDS

This article co-authored by a number of scientists, ASAM physicians, clinicians, treatment center owners, geneticists, neurobiologists, psychologists, social workers, criminologists, nurses, nutritionist, and students, is dedicated to all the people who have lost loved ones in substance-abuse and "reward deficiency syndrome" related tragedies. Why are we failing at reducing the incidence of 'Bad Behaviors'? Are we aiming at the wrong treatment targets for behavioral disorders? We are proposing a paradigm shift and calling it "Reward Deficiency Solution System" providing evidence for its adoption.

While numerous studies support the efficacy of methadone and buprenorphine for the stabilization and maintenance of opioid dependence, clinically significant opioid withdrawal symptoms occur upon tapering and cessation of dosage. We present a case study of a 35 year old Caucasian female (Krissie) who was prescribed increasing dosages of prescription opioids after carpel tunnel surgery secondary to chronic pain from reflex sympathetic dystrophy and fibromyalgia. Over the next 5 years, daily dosage requirements increased to over 80 mg of Methadone and 300 ug/hr Fentanyl transdermal patches, along with combinations of 12-14 1600 mcg Actig lollipop and oral 100 mg Morphine and 30 mg oxycodone 1-2 tabs q4-6hr PRN for breakthrough pain. Total monthly prescription costs including supplemental benzodiazepines, hypnotics and stimulants exceeded $50,000. The patient was subsequently transferred to Suboxone® in 2008, and the dosage was gradually tapered until her admission for inpatient detoxification with KB220Z a natural dopaminergic agonist. We carefully documented her withdrawal symptoms when she precipitously stopped taking buprenorphine/naloxone and during follow-up while taking KB220Z daily. We also genotyped the patient using a reward gene panel including (9 genes 18 alleles): DRD 2,3,4; MOA-A; COMT; DAT1; 5HTTLLR; OPRM1; and GABRA3. At 432 days post Suboxone® withdrawal the patient is being maintained on KB220Z, has been urine tested and is opioid free. Genotyping data revealed a moderate genetic risk for addiction showing a hypodopaminergic trait. This preliminary case data suggest that the daily use of KB220Z could provide a cost effective alternative substitution adjunctive modality for Suboxone®. We encourage double-blind randomized -placebo controlled studies to test the proposition that KB220Z may act as a putative natural opioid substitution maintenance adjunct.

Importantly, research from our laboratory in both in-patient and outpatient facilities utilizing the Comprehensive Analysis of Reported Drugs (CARD)™ found a significant lack of compliance to prescribed treatment medications and a lack of abstinence from drugs of abuse during active recovery. This unpublished, ongoing research provides an impetus to develop accurate genetic diagnosis and holistic approaches that will safely activate brain reward circuitry in the mesolimbic dopamine system. Our laboratory has extensively published the neurogentics of brain reward systems with particular reference to genes related to dopaminergic function. In 1996, we coined “Reward Deficiency Syndrome” (RDS), used to describe behaviors found to have an association with gene-based hypodopaminergic function. Many subsequent studies have embraced RDS as a useful concept to help expand our understanding of Substance Use Disorder (SUD), process addictions, and other obsessive, compulsive and impulsive behaviors. Here, we illustrate the usefulness of the genetic testing of a panel of reward-related genes, the Genetic Addiction Risk Score (GARS) in only one case study. Interestingly, we were able to describe lifetime RDS behaviors in a recovery addict (17 years sober) blindly by just assessing resultant GARS data. We encourage further required studies in this important emerging field.

In accord with the new definition of addiction published by American Society of Addiction Medicine (ASAM) it is well-known that individuals who present to a treatment center involved in chemical dependency or other documented reward dependence behaviors have impaired brain reward circuitry. They have hypodopaminergic function due to genetic and/or environmental negative pressures upon the reward neuro-circuitry. This impairment leads to aberrant craving behavior and other behaviors such as Substance Use Disorder (SUD). Neurogenetic research in both animal and humans revealed that there is a well-defined cascade in the reward site of the brain that leads to normal dopamine release. This cascade has been termed the "Brain Reward Cascade" (BRC). Any impairment due to either genetics or environmental influences on this cascade will result in a reduced amount of dopamine release in the brain reward site. Manipulation of the BRC has been successfully achieved with neuro-nutrient therapy utilizing nutrigenomic principles. After over four decades of development, neuro-nutrient therapy has provided important clinical benefits when appropriately utilized. This is a review, with some illustrative case histories from a number of addiction professionals, of certain molecular neurobiological mechanisms which if ignored may lead to clinical complications.

Mindful of the new evolutionary ideas related to an emerging scientific focus known as omics, we propose that spiritual, social, and political behaviors may be tied in part to inheritable reward gene polymorphisms, as has been demonstrated for the addictions. If so, analyses of gene polymorphisms may assist in predicting liberalism or conservatism in partisan attachments. For example, both drinking (alcohol) and obesity seem to cluster in large social networks and are influenced by friends having the same genotype, in particular the DRD2 A1 allele. Likewise, voting, voting turnout and attachment to a particular political ideology is differentially related to various reward genes (e.g., 5HTT, MOA, DRD2, and DRD4), possibly predicting liberalism or conservatism. Moreover, voters' genetic information may predict presidential outcomes more than the actual issues at hand or the presidential candidates themselves. Thus, political discussions on TV, radio, or other media may be morphed by one's reward gene polymorphisms and as such, may explain the prevalence of generations of die-hard republicans and equally entrenched democratic legacies. Indeed, even in politics, birds of a feather (homophily) flock together. We caution that our proposal should be viewed mindfully awaiting additional research before definitive statements or conclusions can be derived from the studies to date, and we encourage large scale studies to confirm these earlier reports.

This article will touch on theories, scientific research and conjecture about the evolutionary genetics of the brain function and the impact of genetic variants called polymorphisms on drug-seeking behavior. It will cover the neurological basis of pleasure-seeking and addiction, which affects multitudes in a global atmosphere where people are seeking "pleasure states".