Ziv Government Medical Center

Ẕefat, Israel

Ziv Government Medical Center

Ẕefat, Israel
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Blum K.,Florida College | Blum K.,G and listic Addiction Treatment Center | Blum K.,LifeGen Inc | Blum K.,Path Foundation NY | And 20 more authors.
IIOAB Journal | Year: 2011

The total population of the United States at the turn of the 21 st century was 281,421,906. The total number of people above the age of 12 years old was estimated at 249 million. The National Institutes on Drug Abuse and the Substance Abuse and Mental Health Services Administration (SAMHSA) have surveyed persons age 12 and older and found that in the year 2001, a total of 104 million people have used illegal drugs in their life (ever used), 32 million used a psychoactive drug in the past year (2000-2001) and 18 million used a psychoactive drug in the past 30 days. Interestingly this does not include Alcohol. We must ask then, who are the people that could just say NO? When almost half-of the US population have indulged in illegal drug practices, when our presidential candidates are forced to dodge the tricky question of their past history involving illegal drug use, and when almost every American has sloshed down a martini or two in their life time, there must be a reason, there must be a need, there must be a natural response for humans to imbibe at such high rates. There is even a more compelling question surrounding the millions who seek out high risk novelty. Why do millions have this innate drive in face of putting themselves in harms-way? Why are millions paying the price of their indiscretions in our jails, in hospitals, in wheel chairs and are lying dead in our cemeteries. What price must we pay for pleasure seeking or just plain getting "HIGH"? Maybe the answer lies within our brain. Maybe it is in our genome? Utilization of the candidate vs the common variant approach may be parsimonious as it relates to unraveling the addiction riddle. In this commentary we have discussed evidence, theories and conjecture about the "High Mind" and its relationship to evolutionary genetics and drug seeking behavior as impacted by genetic polymorphisms. We consider the meaning of recent findings in genetic research including an exploration of the candidate vs the common variant approach to addiction, epigenetics, genetic memory and the genotype-phenotype problem. We speculate about the neurological basis of pleasure seeking and addiction, the human condition and the scope of societal judgments that effect multitudes in a global atmosphere where people are seeking "pleasure states". ©IIOAB-India.

Blum K.,University of Florida | Blum K.,G and listic Addiction Treatment Center | Blum K.,University of Colorado at Boulder | Blum K.,Reward Deficiency Solutions LLC | And 16 more authors.
IIOAB Journal | Year: 2010

There is a need to classify patients at genetic risk for drug seeking behavior prior to or upon entry to residential and or non-residential chemical dependency programs. We have determined based on a literature review, that there are seven risk alleles associated with six candidate genes that were studied in this patient population of recovering poly-drug abusers. To determine risk severity of these 26 patients we calculated the percentage of prevalence of the risk alleles and provided a severity score based on percentage of these alleles. Subjects carry the following risk alleles: DRD2=A1; SLC6A3 (DAT) =10R; DRD4=3R or 7R; 5HTTlRP = L or LA; MAO= 3R; and COMT=G. As depicted in table 2 low severity (LS) = 1-36%; Moderate Severity =37-50%, and High severity = 51-100%. We studied two distinct ethnic populations group 1 consisted of 16 male Caucasian psycho stimulant addicts and group 2 consisted of 10 Chinese heroin addicted males. Based on this model the 16 subjects tested have at least one risk allele or 100%. Out of the 16 subjects we found 50% (8) HS; 31% (5) MS; and 19% LS (3 subjects). These scores are then converted to a fraction and then represented as a Genetic Addiction Risk Score (GARS) whereby we found the average GARS to be: 0.28 low severity, 0.44 moderate severity and 0.58 high severity respectively. Therefore, using this GARS we found that 81% of the patients were at moderate to high risk for addictive behavior. Of particular interest we found that 56% of the subjects carried the DRD2 A1 allele (9/16). Out of the 9 Chinese heroin addicts[one patient not genotyped] (group 2) we found 11% (1) HS; 56% (5) MS; and 33% LS (3 subjects). These scores are then converted to a fraction and then represented as GARS whereby we found the average GARS to be: 0.28 Low Severity; 0.43 moderate severity and 0.54 high severity respectively. Therefore, using GARS we found that 67% of the patients were at moderate to high risk for addictive behavior. Of particular interest we found that 56% of the subjects carried the DRD2 A1 allele (5/9) similar to group 1. Statistical analysis revealed that the groups did not differ interms of overall severity (67 vs. 81%) in these two distinct populations. Combining these two independent study populations reveal that subjects entering a residential treatment facility for poly-drug abuse carry at least one risk allele (100%). We found 74% of the combined 25 subjects (Caucasian and Chinese) had a moderate to high GARS. Confirmation of these exploratory results and development of mathematical predictive values of these risk alleles are necessary before any meaningful interpretation of these results are to be considered. ©IIOAB-India.

Blum K.,University of Florida | Blum K.,LifeGen Inc | Blum K.,Path Research and Medical Foundation | Blum K.,G and listic Treatment Center | And 11 more authors.
Medical Hypotheses | Year: 2010

Using fMRI, Menon and Levitin [9] clearly found for the first time that listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the nucleus accumbens (NAc) and the ventral tegmental area (VTA), as well as the hypothalamus, and insula, which are thought to be involved in regulating autonomic and physiological responses to rewarding and emotional stimuli. Importantly, responses in the NAc and VTA were strongly correlated pointing to an association between dopamine release and NAc response to music. Listing to pleasant music induced a strong response and significant activation of the VTA-mediated interaction of the NAc with the hypothalamus, insula, and orbitofrontal cortex. Blum et al. [10] provided the first evidence that the dopamine D2 receptor gene (DRD2) Taq 1 A1 allele significantly associated with severe alcoholism whereby the author's suggested that they found the first "reward gene" located in the mesolimbic system. The enhanced functional and effective connectivity between brain regions mediating reward, autonomic, and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. However, little is known about why some people have a more or less powerful mesolimbic experience when they are listening to music. It is well-known that music may induce an endorphinergic response that is blocked by naloxone, a known opioid antagonist (Goldstein [19]). Opioid transmission in the NAc is associated with dopamine release in the VTA. Moreover, dopamine release in the VTA is linked to polymorphisms of the DRD2 gene and even attention-deficit hyperactivity disorder (ADHD), whereby carriers of the DRD2 A1 allele show a reduced NAc release of dopamine (DA). Thus it is conjectured that similar mechanisms in terms of adequate dopamine release and subsequent activation of reward circuitry by listening to music might also be affected by an individual's D2 density in the VTA mediated interaction of the NAc. It is therefore hypothesized that carriers of DRD2 A1 allele may respond significantly differently to carriers of the DRD2 A2 genotype. In this regard, carriers of the D2 A1 allele have a blunted response to glucose and monetary rewards. In contrast powerful D2 agonists like bromocryptine show a heightened activation of the reward circuitry only in DRD2 A1 allele carriers. If music causes a powerful activation in spite of the DRD2 A1 allele due to a strong DA neuronal release which subsequently impinges on existing D2 receptors, then it is reasonable to assume that music is a strong indirect D2 agonist (by virtue of DA neuronal release in the NAc) and may have important therapeutic applicability in Reward Deficiency Syndrome (RDS) related behaviors including Substance Use Disorder (SUD). Ross et al. [18] found that music therapy appears to be a novel motivational tool in a severely impaired inpatient sample of patients with co-occurring mental illness and addiction. © 2009 Elsevier Ltd.

Miller D.K.,LifeStream Solutions Inc | Miller D.K.,Bridging the Gaps Treatment Center | Miller D.K.,LifeGen Inc | Bowirrat A.,Ziv Government Medical Center | And 15 more authors.
Postgraduate Medicine | Year: 2010

It is well established that in both food- and drug-addicted individuals, there is dopamine resistance due to an association with the DRD2 gene A1 allele. Evidence is emerging whereby the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may find its place in recovery from reward deficiency syndrome (RDS) in patients addicted to psychoactive chemicals. Utilizing quantitative electroencephalography (qEEG) as an imaging tool, we show the impact of Synaptamine Complex Variant KB220™ as a putative activator of the mesolimbic system. We demonstrate for the first time that its intravenous administration reduces or "normalizes" aberrant electrophysiological parameters of the reward circuitry site. For this pilot study, we report that the qEEGs of an alcoholic and a heroin abuser with existing abnormalities (ie, widespread theta and widespread alpha activity, respectively) during protracted abstinence are significantly normalized by the administration of 1 intravenous dose of Synaptamine Complex Variant KB220™. Both patients were genotyped for a number of neurotransmitter reward genes to determine to what extent they carry putative dopaminergic risk alleles that may predispose them for alcohol or heroin dependence, respectively. The genes tested included the dopamine transporter (DAT1, locus symbol SLC6A3), dopamine D4 receptor exon 3 VNTR (DRD4), DRD2 TaqIA (rs1800497), COMT val158 met SNP (rs4680), monoamine oxidase A upstream VNTR (MAOA-uVNTR), and serotonin transporter-linked polymorphic region (5HTTLPR, locus symbol SLC6A4). We emphasize that these are case studies, and it would be unlikely for all individuals to carry all putative risk alleles. Based on previous research and our qEEG studies (parts 1 and 2 of this study), we cautiously suggest that long-term activation of dopaminergic receptors (ie, DRD2 receptors) will result in their proliferation and lead to enhanced "dopamine sensitivity" and an increased sense of happiness, particularly in carriers of the DRD2 A1 allele. This is supported by a clinical trial on Synaptamine Complex Variant KB220™ using intravenous administration in. 600 alcoholic patients, resulting in significant reductions in RDS behaviors. It is also confirmed by the expanded oral study on Synaptose Complex KB220Z™, published as part 2 of this study. Future studies must await both functional magnetic resonance imaging and positron emission tomography scanning to determine the acute and chronic effects of oral KB220™ on numbers of D2 receptors and direct interaction at the nucleus accumbens. Confirmation of these results in large, population-based, case-controlled experiments is necessary. These studies would provide important information that could ultimately lead to significant improvement in recovery for those with RDS and dopamine deficiency as a result of a multiple neurotransmitter signal transduction breakdown in the brain reward cascade. © Postgraduate Medicine.

Bowirrat A.,Ziv Medical Center | Chen T.J.H.,Chang Jung Christian University | Blum K.,University of Florida | Blum K.,Reward Deficiency Solutions LLC | And 14 more authors.
Current Neuropharmacology | Year: 2010

Background and Hypothesis: Although the biological underpinnings of immediate and protracted traumarelated responses are extremely complex, 40 years of research on humans and other mammals have demonstrated that trauma (particularly trauma early in the life cycle) has long-term effects on neurochemical responses to stressful events. These effects include the magnitude of the catecholamine response and the duration and extent of the cortisol response. In addition, a number of other biological systems are involved, including mesolimbic brain structures and various neurotransmitters. An understanding of the many genetic and environmental interactions contributing to stress-related responses will provide a diagnostic and treatment map, which will illuminate the vulnerability and resilience of individuals to Posttraumatic Stress Disorder (PTSD). Proposal and Conclusions: We propose that successful treatment of PTSD will involve preliminary genetic testing for specific polymorphisms. Early detection is especially important, because early treatment can improve outcome. When genetic testing reveals deficiencies, vulnerable individuals can be recommended for treatment with “body friendly” pharmacologic substances and/or nutrients. Results of our research suggest the following genes should be tested: serotoninergic, dopaminergic (DRD2, DAT, DBH), glucocorticoid, GABAergic (GABRB), apolipoprotein systems (APOE2), brain-derived neurotrophic factor, Monamine B, CNR1, Myo6, CRF-1 and CRF-2 receptors, and neuropeptide Y (NPY). Treatment in part should be developed that would up-regulate the expression of these genes to bring about a feeling of well being as well as a reduction in the frequency and intensity of the symptoms of PTSD. ©2010 Bentham Science Publishers Ltd.

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