Are We Getting High Cause the Thrill is Gone?

Kenneth Blum; Thomas Mclaughlin; Mark S Gold; Marjorie C Gondre-Lewis; Panayotis K Thanos; Igor Elman; David Baron; Abdalla Bowirrat; Debamyla Barh; Jag Khalsa; Colin Hanna; Nicole Jafari; Foojan Zeine; Eric R Braverman; Catherine Dennen; Milan T Makale; Miles Makale; Keerthy Sunder; Kevin T Murphy; Rajendra D Badgaiyan

Are We Getting High Cause the Thrill is Gone?

J Addict Psychiatry. 2023;7(1):5-516. Epub 2023 Dec 8.

Authors

Kenneth Blum^{1

2

3

4

5

6

7

8

9}, Thomas Mclaughlin¹, Mark S Gold¹⁰, Marjorie C Gondre-Lewis¹¹, Panayotis K Thanos¹², Igor Elman¹³, David Baron², Abdalla Bowirrat⁴, Debamyla Barh⁹, Jag Khalsa¹⁴, Colin Hanna¹², Nicole Jafari^{8

15}, Foojan Zeine^{16

17}, Eric R Braverman¹, Catherine Dennen¹⁸, Milan T Makale¹⁹, Miles Makale²⁰, Keerthy Sunder^{5

21}, Kevin T Murphy²², Rajendra D Badgaiyan²³

Affiliations

¹ The Kenneth Blum Behavioral and Neurogenetic Institute, LLC., Austin, TX, USA.
² Center for Sports, Exercise, Psychiatry, Western University Health Sciences, Pomona, CA, USA.
³ Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.
⁴ Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel.
⁵ The Sunder Foundation, Palm Springs, CA, USA.
⁶ Department of Psychiatry, University of Vermont School of Medicine, Burlington, VY, USA.
⁷ Department of Psychiatry, Wright University, Boonshoff School of Medicine, Dayton, OH, USA.
⁸ Division of Personalized Medicine, Cross-Cultural Research and Educational Institute, San Clemente, CA, USA.
⁹ Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal, India.
¹⁰ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
¹¹ Department of Anatomy, Howard University College of Medicine, Washington D.C., USA.
¹² Behavioral Neuropharmacology and Neuroimaging Laboratory on Addiction, Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY, USA.
¹³ Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.
¹⁴ Division of Therapeutics and Medical Consequences, Medical Consequences of Drug Abuse and Infections Branch, NIDA-NIH, Special Volunteer, Gaithersburg, MD, USA.
¹⁵ Department of Applied Clinical Psychology, The Chicago School of Professional Psychology, Los Angeles, CA, USA.
¹⁶ Department of Health Science, California State University at Long Beach, Long Beach, CA, USA.
¹⁷ Awareness Integration Institute, San Clemente, CA, USA.
¹⁸ Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA.
¹⁹ Department of Radiation Medicine and Applied Sciences, UC San Diego, La Jolla, CA, USA.
²⁰ Department of Psychology, UC San Diego, La Jolla, CA, USA.
²¹ Department of Psychiatry, University of California Riverside, Riverside, CA, USA.
²² Department of Radiation Oncology, University of California, San Diego, La Jolla, USA.
²³ Department of Psychiatry, Case University, School of Medicine, Cleveland, OH, USA.

PMID: 38164471
PMCID: PMC10758019

Abstract

In the USA alone, opioid use disorder (OUD) affects approximately 27 million people. While the number of prescriptions may be declining due to increased CDC guidance and prescriber education, fatalities due to fentanyl-laced street heroin are still rising. Our laboratory has extended the overall concept of both substance and non-substance addictive behaviors, calling it "Reward Deficiency Syndrome (RDS)." Who are its victims, and how do we get this unwanted disorder? Is RDS caused by genes (Nature), environment (Neuro-epigenetics, Nurture), or both? Recent research identifies resting-state functional connectivity in the brain reward circuitry as a crucial factor. Analogously, it is of importance to acknowledge that the cumulative discharge of dopamine, governed by the nucleus accumbens (NAc) and modulated by an array of additional neurotransmitters, constitutes a cornerstone of an individual's overall well-being. Neuroimaging reveals that high-risk individuals exhibit a blunted response to stimuli, potentially due to DNA polymorphisms or epigenetic alterations. This discovery has given rise to the idea of a diminished 'thrill,' though we must consider whether this 'thrill' may have been absent from birth due to high-risk genetic predispositions for addiction. This article reviews this issue and suggests the general concept of the importance of "induction of dopamine homeostasis." We suggest coupling a validated genetic assessment (e.g., GARS) with pro-dopamine regulation (KB220) as one possible frontline modality in place of prescribing potent addictive opioids for OUD except for short time harm reduction. Could gene editing offer a 'cure' for this undesirable genetic modification at birth, influenced by the environment and carried over generations, leading to impaired dopamine and other neurotransmitter imbalances, as seen in RDS? Through dedicated global scientific exploration, we hope for a future where individuals are liberated from pain and disease, achieving an optimal state of well-being akin to the proverbial 'Garden of Eden'.

Keywords: Dopamine; Functional connectivity; Genetic addiction risk severity; Neurotransmitters; Pro-dopamine regulation; Reward brain circuitry; Thrill is gone.

Abstract

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