North Kingstown, RI, United States
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Blum K.,University of Florida | Blum K.,University of Vermont | Blum K.,Dominion Diagnostics | Blum K.,Malibu Beach Recovery Center | And 6 more authors.
Molecular Neurobiology | Year: 2015

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 and prevent relapse for both substance and non-substance-related addictive behaviors. While the existing FDA-approved medications promote blocking dopamine, we argue that a more prudent paradigm shift should be biphasic—short-term blockade and long-term upregulation, enhancing functional connectivity of brain reward circuits. © 2015, The Author(s).

Smith D.E.,856 Stanyan Street | Smith D.E.,Center Point | Smith D.E.,Dominion Diagnostics
Journal of Psychoactive Drugs | Year: 2012

Prescription drug abuse is increasingly recognized as the United States' fastest growing drug problem, rising dramatically since the early 2000s, and particularly affecting adolescents and young adults. Federal officials are urging legislation to educate physicians about the use and effects of potent narcotics, which are increasingly being prescribed for chronic pain. ASAM developed strategies in the 1980s to identify the small minority of misprescribers and focused educational and retraining efforts on these individuals. As health reform and more prevalent pain management put more primary care physicians in a gatekeeper role to manage the medical care of addicts, these clinicians must become aware of the abuse potential of the powerful narcotics they prescribe. Increased reference to state-maintained controlled medication databases can also reduce misprescribing. © Taylor & Francis Group, LLC.

Gaedigk A.,Childrens Mercy Hospital and Clinics | Fuhr U.,University of Cologne | Johnson C.,Dominion Diagnostics | Berard L.A.,University of Montréal | And 2 more authors.
Pharmacogenomics | Year: 2010

Aims: Allelic variants of cytochrome P450 CYP2D6 (CYP2D6), such as gene deletion, duplication, multiplication and conversion, contribute to the wide range of CYP2D6 activity. Novel gene arrangements were discovered and characterized. Materials & methods: DNA from 32 Caucasian and 59 African-American duplication-positive subjects were analyzed by long-range PCR and genotyping to detect CYP2D7-2D6 hybrid tandem alleles. Novel allelic variants were sequenced and a strategy for the detection and analysis of hybrid genes was refined. Results: CYP2D7-2D6 hybrid tandem alleles were identified in one African-American and four Caucasian subjects. Three novel hybrid genes were found on CYP2D6*1 and CYP2D6*2 duplication backgrounds and designated CYP2D6*76, *77 and *78. CYP2D7to 2D6 conversion occurred in introns 1 and 4, and exon 9. All carried a T-insertion in exon 1 abolishing activity. In Caucasians, four out of 33 (12%) of the duplication-positive alleles were hybrid tandems, three CYP2D6*77 + *2 and one CYP2D6*78 + *2. By contrast, in African-Americans only one of 60 duplication-positive alleles was identified as a hybrid tandem. This allele was designated CYP2D6*76 + *1. Conclusion: Hybrid tandem alleles occur infrequently (<0.25%) in Caucasians, but may explain why not every subject with a CYP2D6 duplication presents with an ultrarapid metabolizer phenotype. © 2010 Future Medicine Ltd.

PubMed | University of Florida and Dominion Diagnostics
Type: Journal Article | Journal: Addiction genetics | Year: 2016

The Brain Reward Cascade (BRC) is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic), may result in addictive behaviors as well as altered pain tolerance. While there are many studies claiming a genetic association with addiction and other behavioral infractions, defined as Reward Deficiency Syndrome (RDS), not all are scientifically accurate and in some case just wrong. Albeit our bias, we discuss herein the facts and fictions behind molecular genetic testing in RDS (including pain and addiction) and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDX), the first test to accurately predict ones genetic risk for RDS.

PubMed | University of Minnesota, Dominion Diagnostics, University of Florida and Nupathways Inc.
Type: Journal Article | Journal: Journal of reward deficiency syndrome | Year: 2016

There are approximately 14,500 clinics and programs in America that provide treatment for all types of addictive behaviors we call Reward Deficiency Syndrome (RDS). While most of these have good intentions to provide needed help to the victims of RDS, we propose herein that most of their efforts, especially during periods of aftercare, are not based on the existing scientific evidence. We use aftercare to refer to any form of program or therapy following primary treatment including 12-Step programs. Very few programs actually provide any evidenced-based treatment approaches during this most vulnerable period in recovery. In this trieste we are suggesting that a hypodopaminergic trait (genetic) and/or state (epigenetic) is critical in terms of continued motivation to use/abuse of alcohol or other drugs and can lead to relapse. While there is evidence for the approved FDA drugs to treat drug addiction (e.g. alcohol, opiates, nicotine) these drugs favor a short-term benefit by blocking dopamine. We argue instead for the utilization of long-term benefits that induce dopamine homeostasis, or in simpler terms normalcy. We suggest that this could be accomplished through a number of holistic modalities including, but not limited to, dopamine-boosting diets, hyper-oxygenation, heavy metal detoxification, exercise, meditation, yoga, and most importantly, brain neurotransmitter balancing with nutraceuticals such as KB220 variants. We embrace 12-step programs and fellowships but not as a stand-alone modality, especially during aftercare. We also provide some scientific basis for why resting state functional connectivity (rsfMRI) is so important and may be the cornerstone in terms of how to treat RDS. We postulate that since drugs, food, smoking, gambling, and even compulsive sexual behavior could reduce rsfMRI then modalities (following required research), that can restore this impaired cross talk between various brain regions (e.g. Nucleus accumbens, cingulate gyrus, hippocampus etc.) should be incorporated into the aftercare plan in all treatment programs in America. Anything less will ultimately lead to the so called revolving door for as many as 90% of treatment participants.

Chambers E.E.,Waters Corporation | Woodcock M.J.,Dominion Diagnostics | Wheaton J.P.,Waters Corporation | Pekol T.M.,Dominion Diagnostics | Diehl D.M.,Waters Corporation
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

Tricyclic antidepressants have been prescribed for the treatment of depression and other disorders since their discovery in the 1950s but have been replaced in recent decades by newer drugs with more favorable side effect profiles. However, for some patients and conditions, tricyclic antidepressants remain the drug of choice. A fast, sensitive, and robust UPLC-MS/MS method for the monitoring of amitriptyline, nortriptyline, imipramine, doxepin, and desipramine in human urine has been developed using a pre-defined and systematic method development approach. The method was developed using sub-2-μm particle technology, providing a state-of-the-art alternative to older methods. Total cycle time was 2.5min. Human urine samples (200μL) were prepared using an Oasis® WCX μElution solid-phase extraction plate, which provided good recovery for all analytes (>92%) and low matrix effects (absolute matrix effects <10%). Standard curves were linear over the range 0.02-250ng/mL with r2 values>0.994. The method was evaluated against current FDA guidelines and was applied to the analysis of patient samples, including an assessment of incurred sample reanalysis (ISR). © 2013 Elsevier B.V.

PubMed | Dominion Diagnostics, Wright State University and Florida College
Type: Journal Article | Journal: Austin addiction sciences | Year: 2016

Dopamine along with other chemical messengers like serotonin, cannabinoids, endorphins and glutamine, play significant roles in brain reward processing. There is a devastating opiate/opioid epidemicin the United States. According to the Centers for Disease Control and Prevention (CDC), at least 127 people, young and old, are dying every day due to narcotic overdose and alarmingly heroin overdose is on the rise. The Food and Drug Administration (FDA) has approved some Medication-Assisted Treatments (MATs) for alcoholism, opiate and nicotine dependence, but nothing for psychostimulant and cannabis abuse. While these pharmaceuticals are essential for the short-term induction of psychological extinction, in the long-term caution is necessary because their use favors blocking dopaminergic function indispensable for achieving normal satisfaction in life. The two institutions devoted to alcoholism and drug dependence (NIAAA & NIDA) realize that MATs are not optimal and continue to seek better treatment options. We review, herein, the history of the development of a glutaminergic-dopaminergic optimization complex called KB220 to provide for the possible eventual balancing of the brain reward system and the induction of dopamine homeostasis. This complex may provide substantial clinical benefit to the victims of Reward Deficiency Syndrome (RDS) and assist in recovery from iatrogenically induced addiction to unwanted opiates/opioids and other addictive behaviors.

Dominion Diagnostics | Date: 2010-02-26

Printed questionnaire and survey to be completed by patients and used for monitoring adherence with patients medications.

Dominion Diagnostics | Date: 2011-08-30

Printed reports providing results of tests performed on patients, including substance detection, analysis, description, and references to authoritative citations, and results of tests performed on patients for medication monitoring.

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