1Center for Exercise and Sport Mental Health, Western University Health Sciences, Pomona, USA 2Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel 3Division of Clinical Neurological Research, The Kenneth Blum Neurogenetic and Behavioral Institute, Austin, USA 4Division of Personalized Pain Therapy Research, Center for Advanced Spine Care of Southern Arizona, Tucson, USA 5Department of Pharmaceutical Sciences, College of Pharmacy, Texas Southern University, Houston, TX, USA 6Department of Surgery, Arizonia University School of Medicine, Tucson, AZ, USA 7Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran 8Department of Psychiatry, Harvard School of Medicine, Cambridge, USA 9Department of Psychiatry, Washington University, School of Medicine, St. Louis, USA 10Department of Family Medicine, Jefferson Health Northeast, Philadelphia, USA 11Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, USA 12Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA 13Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA., USA 14Brain and Behavior Laboratory, Department of Psychology, Curry College, Milton, USA 15Department of Psychiatry, School of Medicine, Yale University, New Haven, USA 16Department of Medicine, University of Maryland School of Medicine, Baltimore, USA 17Department of Psychology, St. John’s University, Queens, NYC, NY, USA 18Division of Personalized Neuromodulation, PeakLogic, LLC., Del MAR, CA, USA 19Department of Radiation Medicine and Applied Sciences, UC San Diego, La Jolla, CA, USA 20Department of Psychiatry, Texas Tech University, Health Sciences, School of Medicine, Midland, TX, USA 21Department of Psychiatry, Mt. Sinai University, Ichan School of Medicine, New York, USA
Dopaminergic dysfunction in reward circuitry is well-documented as a contributor to addictive behaviors. Evidence indicates that changes in synchronous neural activity between brain regions mediating reward and cognitive functions may significantly contribute to substance-related disorders. In this commentary we highlight findings showing that the pro-dopaminergic nutraceutical (KB220) enhances functional connectivity between reward and cognitive brain areas in both animal and human studies. Animal studies demonstrate that KB220 activates important brain reward-related regions, including the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, and prelimbic and infralimbic loci. Kb220 induced significant functional connectivity, enhanced neuroplasticity, and improved dopaminergic functionality within the brain reward circuitry with effects localized to these regions rather than broader distributed across the brain. In abstinent heroin-dependent individuals, acute KB220 administration significantly induced BOLD activation in caudate-accumbens dopaminergic pathways relative to placebo. Furthermore, data from 36 clinical trials and preclinical studies encompassing over 1,000 subjects, demonstrate that KB220 supports “dopamine homeostasis” across various reward deficiency behaviors. Clinical outcomes and quantitative electroencephalogy (qEEG) results underscore KB220’s potential anti-craving/anti-relapse effects in addiction and other psychiatric disorders through direct or indirect dopaminergic modulation. Based on a review of the existing knowledge and further intensive investigation, we propose that instead of relying on mono-pharmaceutical approaches, the scientific community should endorse multi-loci dopaminergic restoration of reward brain circuitry as a fundamental paradigm for addressing mental illness.
Keywords: Quantitative Electroencephalogy (qEEG); KB220; Reward Deficiency (RD); Genome-Wide Association Studies (GWAS); Alcohol Use Disorder (AUD)
Rajendra D Badgaiyan., et al. “Multi-Locus Pro-Dopaminergic Restoration of Reward Brain Circuitry in Reward Deficiency Rescinds Mono-Pharmaceutical Targeting”. EC Neurology 17.7 (2025): 01-21.
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