Menu
Back to Journals » Psychology Research and Behavior Management » Volume 16
Futuristic Exploration of Addiction Neuroscience in the Genomic Era
Authors Blum K , Elman I , Bowirrat A, Baron D, Thanos PK, Hanna C, Badgaiyan RD , Gold MS
Received 12 September 2023
Accepted for publication 14 November 2023
Published 9 December 2023 Volume 2023:16 Pages 4989—4991
DOI https://doi.org/10.2147/PRBM.S439837
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 1
Editor who approved publication: Dr Bao-Liang Zhong
Kenneth Blum,1– 7 Igor Elman,8 Abdalla Bowirrat,1 David Baron,1 Panayotis K Thanos,9 Colin Hanna,9 Rajendra D Badgaiyan,10 Mark S Gold11
1Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel; 2Division of Addiction Research & Education, Center for Exercise Sports, Mental Health, Western University Health Sciences, Pomona, CA, USA; 3Institute of Psychology, Eötvös Loránd University, Budapest, Hungary; 4Department of Psychiatry, Boonshoft School of Medicine, Wright University, Dayton, OH, USA; 5Department of Psychiatry, Human Integrated Services Unit, University of Vermont Center for Clinical & Translational Science, College of Medicine, Burlington, VT, USA; 6Sunder Foundation, Palm Springs, CA, USA; 7PEAKLOGIC, LLC., Del Mar, CA, USA; 8Department of Psychiatry, Harvard College of Medicine, Cambridge, MA, USA; 9Behavioral 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; 10Department of Psychiatry, Case Western Reserve University and MetroHealth System, Cleveland, OH, USA; 11Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
Correspondence: Kenneth Blum, Tel +1 404 234 5433, Email [email protected]
Addiction neuroscience is a multidisciplinary approach to treating substance and non-substance (such as eating disorders) addictive behaviors. Researchers in this field aim to understand the neural mechanisms underlying this disease.1 Over the past 30 or more years, substance use disorder (SUD) research has increased significantly, as has our understanding of the neural and genetic mechanisms of addiction. New methodologies have been developed (both clinical and pre-clinical) to assess molecular and neurochemical changes in neuronal systems. In the case of SUD, it is important to remember that DNA pre-addiction antecedents and unwanted negative insults are due to epigenetics.2,3 While we are not there yet, especially when we are administering opioids to treat opioid dependence as if there is an opioid deficiency,4 new advancements have revealed neurogenetic and epigenetic processes by which molecular, neurobiological, and socio-spiritual factors increase vulnerability and resilience to these behaviors.5,6 For example, an individual’s inability to replace short-term rewards with more beneficial long-term rewards can involve neurological and behavioral disruption.7 Knowledge of the combinative role of genes and environment (epigenetics) can help sway unwanted substances and behavioral addictions.8,9
Overall well-being involves numerous neurotransmitters and second messengers. Their intricate interactions regulate the release of dopamine at post-neuronal sites, such as the Nucleus Accumbens (commonly referred to as the brain’s reward center).10 In 1995, Kenneth Blum introduced the concept of “Reward Deficiency Syndrome” (RDS) to highlight hypo-functionality of dopaminergic brain circuits, presented clinically as a reduction in the capacity to experience pleasure and a super-sensitivity to behavioral drives.11–13 It is now well known that genotypical and acquired hypodopaminergia contributes to the development of RDS.14 Individuals afflicted with RDS often turn to substance abuse in an attempt to alleviate diminished reward symptoms, offering temporary relief from this deficit.15
Yet the ongoing use of such substances exacerbates the deficits over time, ultimately amplifying RDS and stress levels.16 Moreover, RDS deficits can be exacerbated by negative emotions that trigger epigenetic changes. Methylation on chromosomal histones can result in substantial disruption of gene expression.17 Chronic exposure to alcohol and other addictive substances can result in executive functional connectivity deficits in the brain. DRD2 methylation was negatively associated with left and right executive control network connectivity. DRD2 methylation was also associated with severity of alcohol problems, reinforcing a theoretical model in which epigenetics and neurobiology correlates of alcohol consumption and SUD. Positive and nurturing behaviors that bring about beneficial effects on gene expression can be a potential solution, lessening such deep distress to these concerns.18,19 Lastly, shifting the focus from medication prescription towards the restoration of dopaminergic homeostasis (or hedonostasis) may be a complementary therapeutic modality to treat opioid use disorder.
Opioid overdoses kill over 100,000 individuals each year.20 Approximately 800 million people globally express addiction and RDS behaviors, necessitating innovative thinking to address these concerns.21 We strongly believe that preaddiction trait detection through tools such as genetic testing is an essential preventative strategy.22
Currently, at least one approved FDA treatment for OUD is to prescribe powerful opioids which of course can induce unwanted dependence. One major benefit is that this successfully helps reduce harm. However, it is our responsibility as scientists and clinicians to focus on novel ways to combat drug-induced dopamine dysregulation and promote the functional balance of dopamine in the brain. This premise to induce dopamine homeostasis can be accomplished via non-pharmaceutical non-addictive and safer interventions including neuromodulation, nutraceuticals as well as cognitive and mindfulness therapies.
Acknowledgments
The authors appreciate financial support of The Sunder foundation, Palm Springs CA, and Peaklogic, Del Mar, CA.
Author Contributions
KB and IE developed the first draft and AB, DB, PKT, CH, MSG and RDB edited and reviewed and inked comments. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Funding
R41 MD012318/MD/NIMHD NIH HHS/United States. I01 CX000479/CX/CSRD VA/United States.
Disclosure
Dr Blum is the inventor of GARS and KB220 and holds many patents thereof worldwide. Professor Kenneth Blum also reports personal fees from VNI, electronic waveform labs, Peaklogic, and Sunder Foundation. In addition, Professor Kenneth Blum has a patent 10,894,024 with royalties paid to Synapatamine. The authors report no other conflicts of interest in this work.
References
1. Volkow ND, Boyle M. Neuroscience of addiction: relevance to prevention and treatment. Am J Psychiatry. 2018;175(8):729–740. PMID: 29690790. doi:10.1176/appi.ajp.2018.17101174
2. McLellan AT, Koob GF, Volkow ND. Preaddiction-A missing concept for treating substance use disorders. JAMA Psychiatry. 2022;79(8):749–751. PMID: 35793096. doi:10.1001/jamapsychiatry.2022.1652
3. Ahmed R, Blum K, Thanos P. Epigenetic Effects of psychoactive drugs. Curr Pharm Des. 2023;29(27):2124–2139. PMID: 37415372. doi:10.2174/1381612829666230706143026
4. Gold MS, Baron D, Bowirrat A, Blum K. Neurological correlates of brain reward circuitry linked to opioid use disorder (OUD): do homo sapiens acquire or have a reward deficiency syndrome? J Neurol Sci. 2020;418:117137. PMID: 32957037; PMCID: PMC7490287. doi:10.1016/j.jns.2020.117137
5. García-Rivera BR, García-Alcaraz JL, Mendoza-Martínez IA, et al. Influence of COVID-19 pandemic uncertainty in negative emotional states and resilience as mediators against suicide ideation, drug addiction and alcoholism. Int J Environ Res Public Health. 2021;18(24):12891. PMID: 34948502; PMCID: PMC8701151. doi:10.3390/ijerph182412891
6. Maldonado R, Calvé P, García-Blanco A, Domingo-Rodriguez L, Senabre E, Martín-García E. Vulnerability to addiction. Neuropharmacology. 2021;186:108466. PMID: 33482225. doi:10.1016/j.neuropharm.2021.108466
7. Volkow ND, Baler RD. NOW vs LATER brain circuits: implications for obesity and addiction. Trends Neurosci. 2015;38(6):345–352. PMID: 25959611. doi:10.1016/j.tins.2015.04.002
8. Blum K, Noble EP, Sheridan PJ, et al. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA. 1990;263(15):2055–2060. PMID: 1969501. doi:10.1001/jama.1990.03440150063027
9. Cadet JL, Jayanthi S. Epigenetics of addiction. Neurochem Int. 2021;147:105069. PMID: 33992741; PMCID: PMC8260024. doi:10.1016/j.neuint.2021.105069
10. Russell VA. Dopamine hypofunction possibly results from a defect in glutamate-stimulated release of dopamine in the nucleus accumbens shell of a rat model for attention deficit hyperactivity disorder--The spontaneously hypertensive rat. Neurosci Biobehav Rev. 2003;27(7):671–682. PMID: 14624811. doi:10.1016/j.neubiorev.2003.08.010
11. Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Comings DE. Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. Pharmacogenetics. 1995;5(3):121–141. PMID: 7550364. doi:10.1097/00008571-199506000-00001
12. Blum K, Sheridan PJ, Wood RC, et al. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. J R Soc Med. 1996;89(7):396–400. PMID: 8774539; PMCID: PMC1295855. doi:10.1177/014107689608900711
13. Blum K, Bowirrat A, Elman I, et al. Evidence for the DRD2 gene as a determinant of Reward Deficiency Syndrome (RDS). Clin Exp Psychol. 2023;9(4):8–11. PMID: 37560184; PMCID: PMC10411139.
14. Borsook D, Linnman C, Faria V, Strassman AM, Becerra L, Elman I. Reward deficiency and anti-reward in pain chronification. Neurosci Biobehav Rev. 2016;68:282–297. PMID: 27246519. doi:10.1016/j.neubiorev.2016.05.033
15. Fried L, Modestino EJ, Siwicki D, et al. Hypodopaminergia and “Precision Behavioral Management” (PBM): it is a generational family affair. Curr Pharm Biotechnol. 2020;21(6):528–541. PMID: 31820688. doi:10.2174/1389201021666191210112108
16. Baik JH. Stress and the dopaminergic reward system. Exp Mol Med. 2020;52(12):1879–1890. PMID: 33257725; PMCID: PMC8080624. doi:10.1038/s12276-020-00532-4
17. Hagerty SL, York Williams SL, Bidwell LC, et al. DRD2 methylation is associated with executive control network connectivity and severity of alcohol problems among a sample of polysubstance users. Addict Biol. 2020;25(1):e12684. PMID: 30370960; PMCID: PMC7326368. doi:10.1111/adb.12684
18. Green CL, Nahhas RW, Scoglio AA, Elman I. Post-traumatic stress symptoms in pathological gambling: potential evidence of anti-reward processes. J Behav Addict. 2017;6(1):98–101. PMID: 28274137; PMCID: PMC5572998. doi:10.1556/2006.6.2017.006
19. Blum K, Green R, Smith J, Llanos-Gomez L, Baron D, Badgaiyan RD. Hypothesizing high negative emotionality as a function of Genetic Addiction Risk Severity (GARS) Testing in Alcohol Use Disorder (AUD). J Syst Integr Neurosci. 2020;7(2). PMID: 35096419; PMCID: PMC8793765. doi:10.15761/jsin.1000245
20. Traynor JR, Moron JA. Opioid research in the time of the opioid crisis. Br J Pharmacol. 2023;180(7):793–796. PMID: 36813266. doi:10.1111/bph.16043
21. Dennen AC, Blum K, Braverman RE, et al. How to combat the global opioid crisis. CPQ Neurol Psychol. 2023;5(4):93. PMID: 36812107; PMCID: PMC9937628.
22. Downs BW, Blum K, Baron D, et al. Death by opioids: are there non-addictive scientific solutions? J Syst Integr Neurosci. 2019;5(2). PMID: 31824737; PMCID: PMC6904107. doi:10.15761/JSIN.1000211
© 2023 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.
By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.