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of Psychostimulants in the Long-Term</h1> </header> <p class="entry-meta"> </p> <div class="entry-content clearfix"> <div class="italics"><i>Kenneth Blum, Rajendra D. Badgaiyan, Eric R. Braverman, Kristina Dushaj, Mona Li, Peter K. Thanos, Zsolt Demetrovics and Marcelo Febo</i></div> <div class="italics"></div> <div class="italics"></div> <div></div> <p> </p> <div> <p><strong>Abstract</strong></p> </div> <p>Unlike other drugs of abuse such as alcohol, nicotine, opiates/opioids, the FDA has not approved any agent to treat psychostimulant dependence. Certainly, it is widely acceptable that dopaminergic signaling is a key factor in both the initiation and continued motivation to abuse this class of stimulant substances. It is also well accepted that psychostimulants such as cocaine affect not only the release of neuronal dopamine at the nucleus accumbens (NAc), but also has powerful inhibitory actions on the dopamine transporter system. Understandably, certain individuals are at high risk and very vulnerable to abuse this class of substances. Trace-amine-associated receptor 1 (TAAR1) is a G -protein coupled receptor activated by trace amines. The encoded protein responds little or not at all to dopamine, serotonin, epinephrine, or histamine, but responds well to betaphenylethylamine, p-tyramine, octopamine, and tryptamine. This gene is thought to be intronless. TAAR1 agonists reduce the neurochemical effects of cocaine and amphetamines as well as attenuate addiction and abuse associated with these two psychostimulants. The mechanism involves blocking the firing rate of dopamine in the limbic system thereby decreasing a hyperdopaminergic trait/state, whereby the opposite is true for TAAR1 antagonists. Based on many studies, it is accepted that in Reward Deficiency Syndrome (RDS), there is weakened tonic and improved phasic dopamine discharge leading to a hypodopaminergic/ glutamatergic trait. The dopamine pro-complex mixture KB220, following many clinical trials including neuroimaging studies, has been shown to enhance resting state functional connectivity in humans (abstinent heroin addicts), na茂ve rodent models, and regulates extensive theta action in the cingulate gyrus of abstinent psychostimulant abusers. In this article, we are hypothesizing that KB220 may induce its action on resting state functional connectivity, for example, by actually balancing (optimizing) the effects of TAAR1 on the glutamatergic system allowing for optimization of this system. This will lead to a normalized and homeostatic release of NAc dopamine. This proposed optimization, and not enhanced activation of TAAR1, should lead to well-being of the individual. Hyper-activation instead of optimizing the TAAR1 system unfortunately will lead to a prolonged hypodopaminergic state and as such, will cause enhanced craving for not only psychoactive substances, but also other drug-related and even non-drug related RDS behaviors. This hypothesis will require extensive research, which seems warranted based on the global epidemic of drug and behavioral addictions.</p> <div><strong>Published on:</strong> June 29, 2016<br/> <strong>doi:</strong> 10.17756/jrdsas.2016-023<br/> <strong>Citation:</strong> Blum K, Badgaiyan RD, Braverman ER, Dushaj K, Li M, et al. Hypothesizing that, A Pro-Dopamine Regulator (KB220Z) Should Optimize, but Not Hyper-Activate the Activity of Trace Amine-Associated Receptor 1 (TAAR-1) and Induce Anti-Craving of Psychostimulants in the Long-Term.<i>J Reward Defic Syndr Addict Sci</i> 2(1): 14-21.</div> <div class="italics"> </div> <div class="pdfdownloadlink"><img class="alignleft size-full wp-image-507" style="margin: 4px -5px 4px 5px;" src="http://jnanoworld.com/wp-content/uploads/2017/04/pdf-icon-24-e1509106685135-1.png" alt="" width="16" height="16"/><div class="sdm_download_link"><a href="https://jaddictionscience.com/?smd_process_download=1&download_id=370" class="sdm_download green" title="jrdsas-023-kenneth-blum" target="_self">PDF (Download Full text)</a></div></div> <div><div class="sdm_download_count"><span class="sdm_count_number"><strong>574</strong></span><br/><span class="sdm_count_string"> Downloads</span></div><span class="postviews_eachpost"><div class="post-views post-245 entry-meta"> <span class="post-views-label">Views </span> <span class="post-views-count">1,132</span> </div></span></div> <script type="text/javascript">jQuery(document).ready(function($){$.post('https://jaddictionscience.com/wp-admin/admin-ajax.php',{action:'wpt_view_count',id:'245'});});</script><div class="addtoany_share_save_container addtoany_content_bottom"><div class="a2a_kit a2a_kit_size_32 addtoany_list" data-a2a-url="https://jaddictionscience.com/2016/06/29/hypothesizing-that-a-pro-dopamine-regulator-kb220z-should-optimize-but-not-hyper-activate-the-activity-of-trace-amine-associated-receptor-1-taar-1-and-induce-anti-craving-of-psychostimulants-in/" data-a2a-title="Hypothesizing that, A Pro-Dopamine Regulator (KB220Z) Should Optimize, but Not Hyper-Activate the Activity of Trace Amine-Associated Receptor 1 (TAAR-1) and Induce Anti-Craving of Psychostimulants in the Long-Term"><a class="a2a_button_facebook" 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