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      Is Open Access

      Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD

      case-report

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          Abstract

          Background

          Addictive-like behaviors (e.g., hoarding and shopping) may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants as well as elevated stress levels. We, therefore, propose that dopamine homeostasis may be the preferred goal in combating such challenging and unwanted behaviors, when simple dopaminergic activation through potent agonists may not provide any resolution.

          Case presentation

          C.J. is a 38-year-old, single, female, living with her mother. She has a history of substance use disorder as well as attention deficit hyperactivity disorder, inattentive type. She had been stable on buprenorphine/naloxone combination and amphetamine, dextroamphetamine mixed salts for many years when unexpectedly she lost her job for oversleeping and not calling into work. KB200z (a pro-dopamine compound) was added to her regimen for complaints of low drive and motivation. After taking this nutraceutical for 4 weeks, she noticed a marked improvement in her mental status and many behaviors. She noted that her shopping and hoarding addictions had appreciably decreased. Furthermore, her lifelong history of terrifying lucid dreams was eliminated. Finally, she felt more in control; her locus of control shifted from external to more internal.

          Discussion

          The hypothesis is that C.J.’s reported, behavioral, and psychological benefits resulted from the pro-dopamine-regulating effect of KB220Z across the brain reward system.

          Conclusions

          This effect, we surmise, could be the result of a new dopamine balance, across C.J.’s brain reward system. Dopamine homeostasis is an effect of KB220Z seen in both animal and human placebo-controlled fMRI experiments.

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          Most cited references84

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          Imaging dopamine's role in drug abuse and addiction.

          Dopamine is involved in drug reinforcement but its role in addiction is less clear. Here we describe PET imaging studies that investigate dopamine's involvement in drug abuse in the human brain. In humans the reinforcing effects of drugs are associated with large and fast increases in extracellular dopamine, which mimic those induced by physiological dopamine cell firing but are more intense and protracted. Since dopamine cells fire in response to salient stimuli, supraphysiological activation by drugs is experienced as highly salient (driving attention, arousal, conditioned learning and motivation) and with repeated drug use may raise the thresholds required for dopamine cell activation and signaling. Indeed, imaging studies show that drug abusers have marked decreases in dopamine D2 receptors and in dopamine release. This decrease in dopamine function is associated with reduced regional activity in orbitofrontal cortex (involved in salience attribution; its disruption results in compulsive behaviors), cingulate gyrus (involved in inhibitory control; its disruption results in impulsivity) and dorsolateral prefrontal cortex (involved in executive function; its disruption results in impaired regulation of intentional actions). In parallel, conditioning triggered by drugs leads to enhanced dopamine signaling when exposed to conditioned cues, which then drives the motivation to procure the drug in part by activation of prefrontal and striatal regions. These findings implicate deficits in dopamine activity-inked with prefrontal and striatal deregulation-in the loss of control and compulsive drug intake that results when the addicted person takes the drugs or is exposed to conditioned cues. The decreased dopamine function in addicted individuals also reduces their sensitivity to natural reinforcers. Therapeutic interventions aimed at restoring brain dopaminergic tone and activity of cortical projection regions could improve prefrontal function, enhance inhibitory control and interfere with impulsivity and compulsive drug administration while helping to motivate the addicted person to engage in non-drug related behaviors.
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            Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior.

            Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions.
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              The dopamine theory of addiction: 40 years of highs and lows.

              For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum. There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels. Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.
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                Author and article information

                Journal
                jba
                JBA
                Journal of Behavioral Addictions
                J Behav Addict
                Akadémiai Kiadó (Budapest )
                2062-5871
                2063-5303
                09 January 2018
                March 2018
                : 7
                : 1
                : 192-203
                Affiliations
                [ 1 ]Department of Psychopharmacology, Center for Psychiatric Medicine , Lawrence, MA, USA
                [ 2 ]Department of Psychiatry, Boonshoft School of Medicine, Dayton VA Medical Center, Wright State University , Dayton, OH, USA
                [ 3 ]Department of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine , Gainesville, FL, USA
                [ 4 ]Department of Psychiatry and Behavioral Sciences, Keck Medicine University of Southern California , Los Angeles, CA, USA
                [ 5 ]Division of Applied Clinical Research & Education, Dominion Diagnostics, LLC , North Kingstown, RI, USA
                [ 6 ]Department of Precision Medicine, Geneus Health LLC , San Antonio, TX, USA
                [ 7 ]Department of Addiction Research & Therapy, Nupathways Inc. , Innsbrook, MO, USA
                [ 8 ]Department of Clinical Neurology, Path Foundation , New York, NY, USA
                [ 9 ]Division of Neuroscience Based Addiction Therapy, The Shores Treatment & Recovery Center , Port Saint Lucie, FL, USA
                [ 10 ] Institute of Psychology, Eötvös Loránd University , Budapest, Hungary
                [ 11 ]Department of Psychology, Curry College , Milton, MA, USA
                [ 12 ]Department of Psychiatry, Icahn School of Medicine , Staten Island, NY, USA
                Author notes
                [* ]Corresponding author: Edward Justin Modestino, PhD; Department of Psychology, Curry College, 1071 Bluehill Avenue, Milton, MA 02186, USA; Phone: +1 617 333 2226; Fax: +1 617 333 2316; E-mail: edward.modestino@ 123456gmail.com
                Article
                10.1556/2006.6.2017.081
                6035027
                29316800
                862cb531-445f-4cc8-ad42-cbb6566c42cc
                © 2018 The Author(s)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes – if any – are indicated.

                History
                : 09 July 2017
                : 04 September 2017
                : 16 October 2017
                : 27 November 2017
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 77, Pages: 12
                Funding
                Funding sources: Drs. KB and ERB are co-recipients of a grant from The Life Extension Foundation, Ft. Lauderdale, FL, USA to Path Foundation, NY, USA. Dr. RDB is supported by the National Institutes of Health grants 1R01NS073884 and 1R21MH073624.
                Categories
                CASE REPORT

                Evolutionary Biology,Medicine,Psychology,Educational research & Statistics,Social & Behavioral Sciences
                reward deficiency syndrome (RDS),attention-deficit/hyperactivity disorder (ADHD),pro-dopamine regulation (KB220Z),hoarding and shopping behaviors

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