EC Neurology

Review Article Volume 17 Issue 11 - 2025

Inducing Dopamine Homeostasis to Combat Brain-Gut Functional Impairment as a Function of Behavioral and Neurogenetic Correlates of Reward Deficiency Syndrome (RDS)

Kenenth Blum1-7*, Kai-Uwe-Lewandrowski1,8, Morgan P Lorio9, Alireza Sharafshah10, Kavya Mohankumar4, Nicole Jafari11, Foojan Zeine12, John Giordano4, Alvaro Dowling13,14, Rafaela Dowling15, Panayotis K Thanos16, Igor Elman17, Rossano Kepler Alvim Fiorelli 5,  Sergio Schmidt5, Debasis Bagchi18, Marco Lindenau4 and Rajendra D Badgaiyan19

1Division Personalized Pain Research and Education, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ, USA

2Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Center, Dayton, OH, USA

3Department of Psychiatry, Human Integrated Services Unit, University of Vermont Center for Clinical and Translational Science, College of Medicine, Burlington, VT, USA

4The Kenneth Blum Behavioral and Neurogenetic Institute, LLC., Austin, TX, USA

5Post-Graduate Program in Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil

6Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel

7Eotvos Lorand University, Institute of Psychology, Department of Clinical Psychology and Addiction, Budapest, Hungary

8Department of Spine Surgery, University of Arizonia, School of Medicine, Tucson, AZ, USA

9Department of Osteopathic Principles and Practice, Orlando College of Osteopathic Medicine, Orlando, FL, USA

10Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

11Department of Applied Clinical Psychology, The Chicago School of Professional Psychology, Los Angeles, CA, USA

12Department of Health Science, California State University at Long Beach, Long Beach, CA, USA

13Orthopaedic Spine Surgeon, Director of Endoscopic Spine Clinic, Santiago, Chile

14Department of Orthopaedic Surgery, USP, Ribeirão Preto, Brazil

15Catacell, Santiago de Chile, Chile

16Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA

17Department of Psychiatry, Harvard University School of Medicine, Cambridge, MA, USA

18Department of Pharmaceutical Sciences, Texas Southern University College of Pharmacy, Houston, TX, USA

19Department of Psychiatry, Mt. Sinai University School of Medicine, New York City, NY, USA

*Corresponding Author: Kenenth Blum, Division Personalized Pain Research and Education, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ, USA.
Received: September 18, 2025; Published: October 15, 2025



Reward Deficiency Syndrome (RDS) encompasses a spectrum of addictive and compulsive behaviors, including substance use disorders, obesity, and behavioral addictions, rooted in dysregulated dopaminergic and endorphinergic pathways. Genetic, epigenetic, and environmental factors interact to compromise the Brain Reward Cascade (BRC), resulting in hypodopaminergia and impaired endogenous opioid signaling. Polymorphisms in key genes, such as DRD2, PENK, and OPRM1, along with epigenetic modifications, can reduce dopamine or endorphin function, increasing vulnerability to compulsive behaviors and addiction. Animal and human studies demonstrate overlapping neurobiological mechanisms across substance and non-substance addictions, implicating the mesolimbic system, prefrontal cortex, and hypothalamic-gut axis. Obesity, as a subtype of RDS, illustrates the interplay of homeostatic and hedonic reinforcement, with metabolic hormones like leptin and ghrelin modulating ventral tegmental area (VTA) dopamine activity. Food and drug addictions share common neurogenetic pathways, and gene-environment interactions influence the propensity for addictive behaviors, including post-bariatric surgery “addiction transfer”. Emerging strategies focus on pro-dopamine regulation, aiming to restore dopaminergic homeostasis through nutraceuticals, lifestyle interventions, and personalized medicine. Genetic Addiction Risk Severity (GARS) testing enables early identification of at-risk individuals, informing targeted prevention and treatment approaches. Policy recommendations emphasize safe, evidence-based integration of pro-dopamine therapies with behavioral and pharmacologic interventions, ensuring quality, transparency, and equitable access. Collectively, these findings underscore the importance of understanding the neurogenetic underpinnings of RDS to develop individualized, mechanistically informed interventions for addiction, obesity, and related disorders.

 Keywords: Dopamine; Brain-Gut Functional Impairment; Reward Deficiency Syndrome (RDS)

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Kenenth Blum., et al. “Inducing Dopamine Homeostasis to Combat Brain-Gut Functional Impairment as a Function of Behavioral and Neurogenetic Correlates of Reward Deficiency Syndrome (RDS)”. EC Neurology  17.11 (2025): 01-25.

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