Kenneth Blum - Academia.edu (original) (raw)

Papers by Kenneth Blum

Research paper thumbnail of The Food and Drug Addiction Epidemic: Targeting Dopamine Homeostasis

Current pharmaceutical design, Jan 22, 2017

Obesity is damaging the lives of more than 300 million people worldwide and maintaining a healthy... more Obesity is damaging the lives of more than 300 million people worldwide and maintaining a healthy weight using popular weight loss tactics remains a very difficult undertaking. Managing the obesity problem seems within reach, as better understanding develops, of the function of our genome in drug/nutrient responses. Strategies indicated by this understanding of nutriepigenomics and neurogenetics in the treatment and prevention of metabolic syndrome and obesity include moderation of mRNA expression by DNA methylation, and inhibition of histone deacetylation. Based on an individual's genetic makeup deficient metabolic pathways can be targeted epigenetically by, for example, the provision of dietary supplementation that includes phytochemicals, vitamins, and importantly functional amino acids. Also, the chromatin structure of imprinted genes that control nutrients during fetal development can be modified. Pathways affecting dopamine signaling, molecular transport and nervous system...

Research paper thumbnail of Treatment of cocaine addiction

Research paper thumbnail of Dopamine D2 gene expression interacts with environmental enrichment to impact lifespan and behavior

Oncotarget, Jan 15, 2016

Aging produces cellular, molecular, and behavioral changes affecting many areas of the brain. The... more Aging produces cellular, molecular, and behavioral changes affecting many areas of the brain. The dopamine (DA) system is known to be vulnerable to the effects of aging, which regulate behavioral functions such as locomotor activity, body weight, and reward and cognition. In particular, age-related DA D2 receptor (D2R) changes have been of particular interest given its relationship with addiction and other rewarding behavioral properties. Male and female wild-type (Drd2 +/+), heterozygous (Drd2 +/-) and knockout (Drd2 -/-) mice were reared post-weaning in either an enriched environment (EE) or a deprived environment (DE). Over the course of their lifespan, body weight and locomotor activity was assessed. While an EE was generally found to be correlated with longer lifespan, these increases were only found in mice with normal or decreased expression of the D2 gene. Drd2 +/+ EE mice lived nearly 16% longer than their DE counterparts. Drd2 +/+ and Drd2 +/- EE mice lived 22% and 21% lon...

Research paper thumbnail of The D2 dopamine receptor gene as a predictor fo compulsive disease: Bayes' theorem

Functional neurology

ABSTRACT

Research paper thumbnail of Reward Deficiency Syndrome (RDS): Is there a Solution?

Journal of Alcoholism & Drug Dependence, 2014

could be classified under three headings: observation and analysis of psychological behaviors; ob... more could be classified under three headings: observation and analysis of psychological behaviors; observation and analysis of cultural and social variables: laboratory investigation into the physiological effects of alcohol on the body.

Research paper thumbnail of Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist Therapy as a Paradigm Shift: Dopamine for Dinner?

Molecular neurobiology, Jan 10, 2015

Everyday, there are several millions of people that are increasingly unable to combat their frust... more Everyday, there are several millions of people that are increasingly unable to combat their frustrating and even fatal romance with getting high and/or experiencing "normal" feelings of well-being. In the USA, the FDA has approved pharmaceuticals for drug and alcohol abuse: tobacco and nicotine replacement therapy. The National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) remarkably continue to provide an increasing understanding of the intricate functions of brain reward circuitry through sophisticated neuroimaging and molecular genetic applied technology. Similar work is intensely investigated on a worldwide basis with enhanced clarity and increased interaction between not only individual scientists but across many disciplines. However, while it is universally agreed that dopamine is a major neurotransmitter in terms of reward dependence, there remains controversy regarding how to modulate its role clinically to treat ...

Research paper thumbnail of Raising Endogenous Brain Levels of Kynurenic Acid May Produce Anti-Reward and Enhance Suicide Ideation

Journal of Alcoholism & Drug Dependence, 2014

Research paper thumbnail of Acute intravenous synaptamine complex variant KB220™ "normalizes" neurological dysregulation in patients during protracted abstinence from alcohol and opiates as observed using quantitative electroencephalographic and genetic analysis for reward polymorphisms: part 1, pilot study with 2 case reports

Postgraduate medicine, 2010

It is well established that in both food- and drug-addicted individuals, there is dopamine resist... more 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…

Research paper thumbnail of Correction: Braverman, E.R., et al. Managing Terrorism or Accidental Nuclear Errors, Preparing for Iodine-131 Emergencies: A Comprehensive Review. Int. J. Environ. Res. Public Health 2014, 11, 4158–4200

International Journal of Environmental Research and Public Health, 2014

The authors wish to make the following amendments to their paper published in International Journ... more The authors wish to make the following amendments to their paper published in International Journal of Environmnetal Research and Public Health [1]: [...]

Research paper thumbnail of The Genetics of Problem and Pathological Gambling: A Systematic Review

Current Pharmaceutical Design, 2014

Research paper thumbnail of Synaptamine (SG8839),TM An Amino-Acid Enkephalinase Inhibition Nutraceutical Improves Recovery of Alcoholics, A Subtype of Reward Deficiency Syndrome (RDS)

Trends in Applied Sciences Research, 2007

Research paper thumbnail of Prolonged P300 latency in a neuropsychiatric population with the D2 Dopamine receptor A1 allele

Pharmacogenetics, 1994

The role of the dopaminergic system in P300 has been implicated and previous studies have suggest... more The role of the dopaminergic system in P300 has been implicated and previous studies have suggested the presence of a heritable component in the genesis of P300 or P3, a late positive component of the event-related potential. In the present investigation, 155 Caucasian male and female diagnosed neuropsychiatrically-ill patients with and without comorbid drug and alcohol abuse/dependence were genotyped for the presence or absence of the A1 allele of the D2 dopamine receptor gene (DRD2). The relationship of the A1 and A2 alleles to P3 amplitude and latency was also determined. The results showed no significant difference in P3 amplitude between all groups studied with A1 and A2 allele carriers. However, we now report prolonged P3 latency in neuropsychiatrically-ill patients (with or without polysubstance abuse) with those carrying two copies of the A1 allele (homozygote) of the DRD2 gene (quadratic trend, p = 0.01). Moreover, the age-adjusted mean P3 latency in the D2A2/A2 allele group was 327.8 +/- 3.08 ms compared by ANOVA, to 360.04 +/- 4.86 ms in the D2A1/A1 group. Our work suggests an association of polymorphisms of the DRD2 gene and a biological marker previously indicated to have predictive value in vulnerability to substance abuse.

Research paper thumbnail of From brain science to brain based medicine

Research paper thumbnail of Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy

Medical Hypotheses, 2004

We decided to test the hypothesis that possibly by combining a narcotic antagonist and amino-acid... more We decided to test the hypothesis that possibly by combining a narcotic antagonist and amino-acid therapy consisting of an enkephalinase inhibitor (D D-phenylalanine) and neurotransmitter precursors (L L-amino-acids) to promote neuronal dopamine release might enhance compliance in methadone patients rapidly detoxified with the narcotic antagonist Trexan â (Dupont, Delaware). In this regard, Thanos et al. [J. Neurochem. 78 (2001) 1094] and associates found increases in the dopamine D2 receptors (DRD2) via adenoviral vector delivery of the DRD2 gene into the nucleus accumbens, significantly reduced both ethanol preference (43%) and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. This DRD2 overexpression similarly produced significant reductions in ethanol non-preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This work further suggests that high levels of DRD2 may be protective against alcohol abuse [JAMA 263 (1990) 2055; Arch, Gen. Psychiatr. 48 (1991) 648]. The DRD2 A1 allele has also been shown to associate with heroin addicts in a number of studies. In addition, other dopaminergic receptor gene polymorphisms have also associated with opioid dependence. For example, Kotler et al. [Mol. Phychiatr. 3 (1997) 251] showed that the 7 repeat allele of the DRD4 receptor is significantly overpresented in the opioid-dependent cohort and confers a relative risk of 2.46. This has been confirmed by Li et al. [Mol. Psychiatry 2 (1997) 413] for both the 5 and 7 repeat alleles in Han Chinese case control sample of heroin addicts. Similarly Duaux et al. [Mol.

Research paper thumbnail of Neuro-chemical activation of brain reward meso-limbic circuitry is associated with relapse prevention and drug hunger: A hypothesis

Medical Hypotheses, 2011

Background: It is no surprise that it has taken over four decades to confirm and extend the cruci... more Background: It is no surprise that it has taken over four decades to confirm and extend the crucial role of dopamine and related genes and gene deficits in the etiology of risk for drug dependence. Hundreds of studies, enabled by neuroscience neuroimaging and genetic advances, have been reported. While dopamine theories have been reported, confirmed, replicated and replicated again, changes have been slow to move from the bench to the bedside. Unlike penicillin used to target certain infections, addiction requires the consent, motivation and enthusiastic participation of the patient. Clearly, current treatment has not caught up with advances in the science. In-patient and outpatient treatment still relies on detoxification, abstinence and 12 step programs. Addiction is a chronic and relapsing disease. Addiction treatment can be reported as cures at 3 or 6 weeks, only to be clearly failures at 1 or 5 years. The logical standard of care should focus on detoxifying, stabilizing and returning the patient to the pre-loss of control or pre-addiction neurochemical state. Method: Pre-clinical and clinical data on neurochemistry and neurogenetics of Substance Use Disorder (SUD) as it relates to both relapse and drug hunger has been reviewed. Results: We are proposing herein that efforts to physiologically integrate known neural mechanisms with other psychotherapeutic treatment options to combat relapse should be encouraged. It is well known that after prolonged abstinence, recovered addicts are particularly vulnerable to relapse. Individuals who use their drug of choice after abstinence experience a powerful euphoria that can quickly precipitate a full-blown relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed ''supersensitivity'' might be the result of pre-morbid or state genetic hypodopaminergic polymorphisms. Hypothesis: We are proposing that recent studies have indicated that genetic, personality and environmental factors are predictors of drug use in adolescents. Exploration of various treatment approaches for the most part reveal poor outcomes in terms of relapse prevention and continued drug hunger. The authors are proposing a new paradigm shift in residential, non-residential and aftercare involving the incorporation of genetic testing to identify risk alleles coupled with D2 receptor stimulation using neuroadatogen amino acid precursor enkephlinase-catecholamine-methyltransferase (COMT) inhibition therapy. A natural but therapeutic nutraceutical formulation potentially induces DA release could cause the induction of D2-directed mRNA and proliferation of D2 receptors in the human. We further hypothesize that this proliferation of D2 receptors in turn will induce the attenuation of drug-like craving behavior. Finally, pharmacological therapies have had limited success because these powerful agents have focused on maintenance or interference with drug euphoria rather than correcting or compensating for pre-morbid dopamine system deficits These concepts await further confirmation via required neuroimaging studies.

Research paper thumbnail of Neurogenetics and Clinical Evidence for the Putative Activation of the Brain Reward Circuitry by a Neuroadaptagen: Proposing an Addiction Candidate Gene Panel Map

Journal of Psychoactive Drugs, 2011

This document presents evidence supporting the role of the KB220/KB220Z neuroadaptagens consistin... more This document presents evidence supporting the role of the KB220/KB220Z neuroadaptagens consisting of amino-acid neurotransmitter precursors and enkephalinase-catecholamine-methyl-transferase (COMT) inhibition therapy called Neuroadaptagen Amino Acid Therapy (NAAT) in brain reward function. It is becoming increasingly clear that this novel formulation is the first neuroadaptagen known to activate the brain reward circuitry. Ongoing research repeatedly confirms the numerous clinical effects that ultimately result in significant benefits for victims having genetic antecedents for all addictive, compulsive and impulsive behaviors. These behaviors are correctly classified under the rubric of"Reward Deficiency…

Research paper thumbnail of Hypothesising that salts of iodine, strontium and caesium reverse ageing induced by nuclear radiation

International Journal of Low Radiation, 2013

Radiation accelerates ageing, producing telomere shortening, metabolic ageing, cell apoptosis, im... more Radiation accelerates ageing, producing telomere shortening, metabolic ageing, cell apoptosis, immunological decline, mitochondrial damage, free radical damage and oxidative stress. Salts of iodine, strontium and caesium may reverse ageing induced by nuclear radiation. The American Thyroid Association (ATA) has established that potassium iodide (KI) needs to be accessible to those within 50 miles of nuclear reactors. Despite ATA recommendations, if you distribute KI at the time of explosion, it may not be effective; thus, it is a preventive measure, not a tertiary treatment. KI treatment is most successful when used prior to radioactive iodine exposure. Weekly supplementation of KI reduces hypothyroidism and thyroid nodules; strontium carbonate (SrCO 3) reduces osteopenia and inadequate bone development; and caesium chloride (CsCl) reduces brain cell apoptosis and anxiety. Low doses of radiation may result in hormesis and improved health. A radiation cleanup plan with further investigation could be implemented as a preventive measure.

Research paper thumbnail of Dopamine D2-receptor gene polymorphisms in scandinavian chronic alcoholics

European Archives of Psychiatry and Clinical Neuroscience, 1994

Alterations in the dopamine system have been hypothesized as a predisposing factor in alcoholism.... more Alterations in the dopamine system have been hypothesized as a predisposing factor in alcoholism. The presence of the TaqI A1 and B1 alleles adjacent to the dopamine D 2-receptor gene (DRD2) was studied in Scandinavian alcoholic inpatients (n = 74), alcoholics autopsied at a forensic clinic (n = 19) and controls (n = 81). There were no significant differences between controls and the alcoholics, but a tendency of increased DRD2 TaqI A1 or B1 allele frequencies in alcoholic groups selected for severity (i.e. severity according to DSM-III-R criteria, early onset or severe medical complications due to alcohol abuse) and decreased frequencies in the corresponding less severe alcoholic group. The present study does not yield evidence for the hypothesis of an association between the DRD2 TaqI A1 or B1 alleles and alcoholism.

Research paper thumbnail of Effects of chromium picolinate supplementation on body composition: a randomized, double-masked, placebo-controlled study

Current Therapeutic Research, 1996

To examine the effect of chromium picolinate (CrP) on body composition, a randomized, double-mask... more To examine the effect of chromium picolinate (CrP) on body composition, a randomized, double-masked, placebo-controlled study was conducted. A total of 154 patients received either a placebo or 200 kg or 400 pg of CrP per day. Subjects were asked to consume at least two servings of a protein/carbohydrate nutritional drink a day that contained the different amounts of CrP. Subjects were free-living and were not provided with weight loss, dietary, or exercise guidance. Body composition was measured before and after the 72-day test period by using underwater testing (displacement method) with residual lung volumes determined by helium dilution. On completion of the posttest, a body composition improvement (BCI) index was calculated for each subject by adding the loss of body fat and gain in nonfat mass and subtracting fat gained and lean lost. Analysis of the prestudy data revealed that there were no significant differences in body composition between the three groups. After the test period, both the 200-pg and 400-pg groups had significantly higher positive changes in BCIs compared with placebo. A single-factor analysis of variance weighted linear trend was also highly significant. No significant differences in BCI were found between the 200-and 400~(rg groups. Supplementation with a minimum of 200 pg/d of chromium (as CrP) can lead to significant improvement in body composition.

Research paper thumbnail of Substance Use Disorder Exacerbates Brain Electrophysiological Abnormalities in a Psychiatrically-III Population

Clinical Electroencephalography, 1996

Objective: To assess by brain electrical activity mapping whether cocaine and alcohol abuse and d... more Objective: To assess by brain electrical activity mapping whether cocaine and alcohol abuse and dependence would exacerbate electrophysiological abnormalities in a psychiatrically-ill population.Design, Setting, and Participants: Utilizing a brain mapping system, we assessed EEG, Spectral Analysis (Quantitative EEG[QEEG]), Evoked Potentials (Auditory and Visual), and P300 (cognitive evoked potential), in a total of 111 probands divided into three groups: controls (N = 16), psychiatrically-ill without comorbid substance use disorder (N = 34), and psychiatrically-ill with comorbid substance use disorder (cocaine and alcohol abuse and dependence) (N = 61), at an outpatient neuropsychiatric clinic. With regard to demographic data, the group participating in this study did not differ significantly. A comparison was made among the groups to assist in differentiating the effects of substance use disorder compared to psychiatric disease on brain electrical activity.Main Outcome Measures: An...

Research paper thumbnail of The Food and Drug Addiction Epidemic: Targeting Dopamine Homeostasis

Current pharmaceutical design, Jan 22, 2017

Obesity is damaging the lives of more than 300 million people worldwide and maintaining a healthy... more Obesity is damaging the lives of more than 300 million people worldwide and maintaining a healthy weight using popular weight loss tactics remains a very difficult undertaking. Managing the obesity problem seems within reach, as better understanding develops, of the function of our genome in drug/nutrient responses. Strategies indicated by this understanding of nutriepigenomics and neurogenetics in the treatment and prevention of metabolic syndrome and obesity include moderation of mRNA expression by DNA methylation, and inhibition of histone deacetylation. Based on an individual's genetic makeup deficient metabolic pathways can be targeted epigenetically by, for example, the provision of dietary supplementation that includes phytochemicals, vitamins, and importantly functional amino acids. Also, the chromatin structure of imprinted genes that control nutrients during fetal development can be modified. Pathways affecting dopamine signaling, molecular transport and nervous system...

Research paper thumbnail of Treatment of cocaine addiction

Research paper thumbnail of Dopamine D2 gene expression interacts with environmental enrichment to impact lifespan and behavior

Oncotarget, Jan 15, 2016

Aging produces cellular, molecular, and behavioral changes affecting many areas of the brain. The... more Aging produces cellular, molecular, and behavioral changes affecting many areas of the brain. The dopamine (DA) system is known to be vulnerable to the effects of aging, which regulate behavioral functions such as locomotor activity, body weight, and reward and cognition. In particular, age-related DA D2 receptor (D2R) changes have been of particular interest given its relationship with addiction and other rewarding behavioral properties. Male and female wild-type (Drd2 +/+), heterozygous (Drd2 +/-) and knockout (Drd2 -/-) mice were reared post-weaning in either an enriched environment (EE) or a deprived environment (DE). Over the course of their lifespan, body weight and locomotor activity was assessed. While an EE was generally found to be correlated with longer lifespan, these increases were only found in mice with normal or decreased expression of the D2 gene. Drd2 +/+ EE mice lived nearly 16% longer than their DE counterparts. Drd2 +/+ and Drd2 +/- EE mice lived 22% and 21% lon...

Research paper thumbnail of The D2 dopamine receptor gene as a predictor fo compulsive disease: Bayes' theorem

Functional neurology

ABSTRACT

Research paper thumbnail of Reward Deficiency Syndrome (RDS): Is there a Solution?

Journal of Alcoholism & Drug Dependence, 2014

could be classified under three headings: observation and analysis of psychological behaviors; ob... more could be classified under three headings: observation and analysis of psychological behaviors; observation and analysis of cultural and social variables: laboratory investigation into the physiological effects of alcohol on the body.

Research paper thumbnail of Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist Therapy as a Paradigm Shift: Dopamine for Dinner?

Molecular neurobiology, Jan 10, 2015

Everyday, there are several millions of people that are increasingly unable to combat their frust... more Everyday, there are several millions of people that are increasingly unable to combat their frustrating and even fatal romance with getting high and/or experiencing "normal" feelings of well-being. In the USA, the FDA has approved pharmaceuticals for drug and alcohol abuse: tobacco and nicotine replacement therapy. The National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) remarkably continue to provide an increasing understanding of the intricate functions of brain reward circuitry through sophisticated neuroimaging and molecular genetic applied technology. Similar work is intensely investigated on a worldwide basis with enhanced clarity and increased interaction between not only individual scientists but across many disciplines. However, while it is universally agreed that dopamine is a major neurotransmitter in terms of reward dependence, there remains controversy regarding how to modulate its role clinically to treat ...

Research paper thumbnail of Raising Endogenous Brain Levels of Kynurenic Acid May Produce Anti-Reward and Enhance Suicide Ideation

Journal of Alcoholism & Drug Dependence, 2014

Research paper thumbnail of Acute intravenous synaptamine complex variant KB220™ "normalizes" neurological dysregulation in patients during protracted abstinence from alcohol and opiates as observed using quantitative electroencephalographic and genetic analysis for reward polymorphisms: part 1, pilot study with 2 case reports

Postgraduate medicine, 2010

It is well established that in both food- and drug-addicted individuals, there is dopamine resist... more 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…

Research paper thumbnail of Correction: Braverman, E.R., et al. Managing Terrorism or Accidental Nuclear Errors, Preparing for Iodine-131 Emergencies: A Comprehensive Review. Int. J. Environ. Res. Public Health 2014, 11, 4158–4200

International Journal of Environmental Research and Public Health, 2014

The authors wish to make the following amendments to their paper published in International Journ... more The authors wish to make the following amendments to their paper published in International Journal of Environmnetal Research and Public Health [1]: [...]

Research paper thumbnail of The Genetics of Problem and Pathological Gambling: A Systematic Review

Current Pharmaceutical Design, 2014

Research paper thumbnail of Synaptamine (SG8839),TM An Amino-Acid Enkephalinase Inhibition Nutraceutical Improves Recovery of Alcoholics, A Subtype of Reward Deficiency Syndrome (RDS)

Trends in Applied Sciences Research, 2007

Research paper thumbnail of Prolonged P300 latency in a neuropsychiatric population with the D2 Dopamine receptor A1 allele

Pharmacogenetics, 1994

The role of the dopaminergic system in P300 has been implicated and previous studies have suggest... more The role of the dopaminergic system in P300 has been implicated and previous studies have suggested the presence of a heritable component in the genesis of P300 or P3, a late positive component of the event-related potential. In the present investigation, 155 Caucasian male and female diagnosed neuropsychiatrically-ill patients with and without comorbid drug and alcohol abuse/dependence were genotyped for the presence or absence of the A1 allele of the D2 dopamine receptor gene (DRD2). The relationship of the A1 and A2 alleles to P3 amplitude and latency was also determined. The results showed no significant difference in P3 amplitude between all groups studied with A1 and A2 allele carriers. However, we now report prolonged P3 latency in neuropsychiatrically-ill patients (with or without polysubstance abuse) with those carrying two copies of the A1 allele (homozygote) of the DRD2 gene (quadratic trend, p = 0.01). Moreover, the age-adjusted mean P3 latency in the D2A2/A2 allele group was 327.8 +/- 3.08 ms compared by ANOVA, to 360.04 +/- 4.86 ms in the D2A1/A1 group. Our work suggests an association of polymorphisms of the DRD2 gene and a biological marker previously indicated to have predictive value in vulnerability to substance abuse.

Research paper thumbnail of From brain science to brain based medicine

Research paper thumbnail of Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy

Medical Hypotheses, 2004

We decided to test the hypothesis that possibly by combining a narcotic antagonist and amino-acid... more We decided to test the hypothesis that possibly by combining a narcotic antagonist and amino-acid therapy consisting of an enkephalinase inhibitor (D D-phenylalanine) and neurotransmitter precursors (L L-amino-acids) to promote neuronal dopamine release might enhance compliance in methadone patients rapidly detoxified with the narcotic antagonist Trexan â (Dupont, Delaware). In this regard, Thanos et al. [J. Neurochem. 78 (2001) 1094] and associates found increases in the dopamine D2 receptors (DRD2) via adenoviral vector delivery of the DRD2 gene into the nucleus accumbens, significantly reduced both ethanol preference (43%) and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. This DRD2 overexpression similarly produced significant reductions in ethanol non-preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This work further suggests that high levels of DRD2 may be protective against alcohol abuse [JAMA 263 (1990) 2055; Arch, Gen. Psychiatr. 48 (1991) 648]. The DRD2 A1 allele has also been shown to associate with heroin addicts in a number of studies. In addition, other dopaminergic receptor gene polymorphisms have also associated with opioid dependence. For example, Kotler et al. [Mol. Phychiatr. 3 (1997) 251] showed that the 7 repeat allele of the DRD4 receptor is significantly overpresented in the opioid-dependent cohort and confers a relative risk of 2.46. This has been confirmed by Li et al. [Mol. Psychiatry 2 (1997) 413] for both the 5 and 7 repeat alleles in Han Chinese case control sample of heroin addicts. Similarly Duaux et al. [Mol.

Research paper thumbnail of Neuro-chemical activation of brain reward meso-limbic circuitry is associated with relapse prevention and drug hunger: A hypothesis

Medical Hypotheses, 2011

Background: It is no surprise that it has taken over four decades to confirm and extend the cruci... more Background: It is no surprise that it has taken over four decades to confirm and extend the crucial role of dopamine and related genes and gene deficits in the etiology of risk for drug dependence. Hundreds of studies, enabled by neuroscience neuroimaging and genetic advances, have been reported. While dopamine theories have been reported, confirmed, replicated and replicated again, changes have been slow to move from the bench to the bedside. Unlike penicillin used to target certain infections, addiction requires the consent, motivation and enthusiastic participation of the patient. Clearly, current treatment has not caught up with advances in the science. In-patient and outpatient treatment still relies on detoxification, abstinence and 12 step programs. Addiction is a chronic and relapsing disease. Addiction treatment can be reported as cures at 3 or 6 weeks, only to be clearly failures at 1 or 5 years. The logical standard of care should focus on detoxifying, stabilizing and returning the patient to the pre-loss of control or pre-addiction neurochemical state. Method: Pre-clinical and clinical data on neurochemistry and neurogenetics of Substance Use Disorder (SUD) as it relates to both relapse and drug hunger has been reviewed. Results: We are proposing herein that efforts to physiologically integrate known neural mechanisms with other psychotherapeutic treatment options to combat relapse should be encouraged. It is well known that after prolonged abstinence, recovered addicts are particularly vulnerable to relapse. Individuals who use their drug of choice after abstinence experience a powerful euphoria that can quickly precipitate a full-blown relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed ''supersensitivity'' might be the result of pre-morbid or state genetic hypodopaminergic polymorphisms. Hypothesis: We are proposing that recent studies have indicated that genetic, personality and environmental factors are predictors of drug use in adolescents. Exploration of various treatment approaches for the most part reveal poor outcomes in terms of relapse prevention and continued drug hunger. The authors are proposing a new paradigm shift in residential, non-residential and aftercare involving the incorporation of genetic testing to identify risk alleles coupled with D2 receptor stimulation using neuroadatogen amino acid precursor enkephlinase-catecholamine-methyltransferase (COMT) inhibition therapy. A natural but therapeutic nutraceutical formulation potentially induces DA release could cause the induction of D2-directed mRNA and proliferation of D2 receptors in the human. We further hypothesize that this proliferation of D2 receptors in turn will induce the attenuation of drug-like craving behavior. Finally, pharmacological therapies have had limited success because these powerful agents have focused on maintenance or interference with drug euphoria rather than correcting or compensating for pre-morbid dopamine system deficits These concepts await further confirmation via required neuroimaging studies.

Research paper thumbnail of Neurogenetics and Clinical Evidence for the Putative Activation of the Brain Reward Circuitry by a Neuroadaptagen: Proposing an Addiction Candidate Gene Panel Map

Journal of Psychoactive Drugs, 2011

This document presents evidence supporting the role of the KB220/KB220Z neuroadaptagens consistin... more This document presents evidence supporting the role of the KB220/KB220Z neuroadaptagens consisting of amino-acid neurotransmitter precursors and enkephalinase-catecholamine-methyl-transferase (COMT) inhibition therapy called Neuroadaptagen Amino Acid Therapy (NAAT) in brain reward function. It is becoming increasingly clear that this novel formulation is the first neuroadaptagen known to activate the brain reward circuitry. Ongoing research repeatedly confirms the numerous clinical effects that ultimately result in significant benefits for victims having genetic antecedents for all addictive, compulsive and impulsive behaviors. These behaviors are correctly classified under the rubric of"Reward Deficiency…

Research paper thumbnail of Hypothesising that salts of iodine, strontium and caesium reverse ageing induced by nuclear radiation

International Journal of Low Radiation, 2013

Radiation accelerates ageing, producing telomere shortening, metabolic ageing, cell apoptosis, im... more Radiation accelerates ageing, producing telomere shortening, metabolic ageing, cell apoptosis, immunological decline, mitochondrial damage, free radical damage and oxidative stress. Salts of iodine, strontium and caesium may reverse ageing induced by nuclear radiation. The American Thyroid Association (ATA) has established that potassium iodide (KI) needs to be accessible to those within 50 miles of nuclear reactors. Despite ATA recommendations, if you distribute KI at the time of explosion, it may not be effective; thus, it is a preventive measure, not a tertiary treatment. KI treatment is most successful when used prior to radioactive iodine exposure. Weekly supplementation of KI reduces hypothyroidism and thyroid nodules; strontium carbonate (SrCO 3) reduces osteopenia and inadequate bone development; and caesium chloride (CsCl) reduces brain cell apoptosis and anxiety. Low doses of radiation may result in hormesis and improved health. A radiation cleanup plan with further investigation could be implemented as a preventive measure.

Research paper thumbnail of Dopamine D2-receptor gene polymorphisms in scandinavian chronic alcoholics

European Archives of Psychiatry and Clinical Neuroscience, 1994

Alterations in the dopamine system have been hypothesized as a predisposing factor in alcoholism.... more Alterations in the dopamine system have been hypothesized as a predisposing factor in alcoholism. The presence of the TaqI A1 and B1 alleles adjacent to the dopamine D 2-receptor gene (DRD2) was studied in Scandinavian alcoholic inpatients (n = 74), alcoholics autopsied at a forensic clinic (n = 19) and controls (n = 81). There were no significant differences between controls and the alcoholics, but a tendency of increased DRD2 TaqI A1 or B1 allele frequencies in alcoholic groups selected for severity (i.e. severity according to DSM-III-R criteria, early onset or severe medical complications due to alcohol abuse) and decreased frequencies in the corresponding less severe alcoholic group. The present study does not yield evidence for the hypothesis of an association between the DRD2 TaqI A1 or B1 alleles and alcoholism.

Research paper thumbnail of Effects of chromium picolinate supplementation on body composition: a randomized, double-masked, placebo-controlled study

Current Therapeutic Research, 1996

To examine the effect of chromium picolinate (CrP) on body composition, a randomized, double-mask... more To examine the effect of chromium picolinate (CrP) on body composition, a randomized, double-masked, placebo-controlled study was conducted. A total of 154 patients received either a placebo or 200 kg or 400 pg of CrP per day. Subjects were asked to consume at least two servings of a protein/carbohydrate nutritional drink a day that contained the different amounts of CrP. Subjects were free-living and were not provided with weight loss, dietary, or exercise guidance. Body composition was measured before and after the 72-day test period by using underwater testing (displacement method) with residual lung volumes determined by helium dilution. On completion of the posttest, a body composition improvement (BCI) index was calculated for each subject by adding the loss of body fat and gain in nonfat mass and subtracting fat gained and lean lost. Analysis of the prestudy data revealed that there were no significant differences in body composition between the three groups. After the test period, both the 200-pg and 400-pg groups had significantly higher positive changes in BCIs compared with placebo. A single-factor analysis of variance weighted linear trend was also highly significant. No significant differences in BCI were found between the 200-and 400~(rg groups. Supplementation with a minimum of 200 pg/d of chromium (as CrP) can lead to significant improvement in body composition.

Research paper thumbnail of Substance Use Disorder Exacerbates Brain Electrophysiological Abnormalities in a Psychiatrically-III Population

Clinical Electroencephalography, 1996

Objective: To assess by brain electrical activity mapping whether cocaine and alcohol abuse and d... more Objective: To assess by brain electrical activity mapping whether cocaine and alcohol abuse and dependence would exacerbate electrophysiological abnormalities in a psychiatrically-ill population.Design, Setting, and Participants: Utilizing a brain mapping system, we assessed EEG, Spectral Analysis (Quantitative EEG[QEEG]), Evoked Potentials (Auditory and Visual), and P300 (cognitive evoked potential), in a total of 111 probands divided into three groups: controls (N = 16), psychiatrically-ill without comorbid substance use disorder (N = 34), and psychiatrically-ill with comorbid substance use disorder (cocaine and alcohol abuse and dependence) (N = 61), at an outpatient neuropsychiatric clinic. With regard to demographic data, the group participating in this study did not differ significantly. A comparison was made among the groups to assist in differentiating the effects of substance use disorder compared to psychiatric disease on brain electrical activity.Main Outcome Measures: An...