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Cited by 3Opioid Use Disorder TreatmentSubstance Abuse Treatment and OutcomesPain Management and Opioid Use

Solving the Global Opioid Crisis: Incorporating Genetic Addiction Risk Assessment with Personalized Dopaminergic Homeostatic Therapy and Awareness Integration Therapy

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Foojan Zeine, Nicole Jafari, David A. Baron, Abdalla Bowirrat, Albert Pinhasov, Brian Norling, Kathleen Carter Martinez, Mohammad Nami +34 more·2024·Journal of Addiction Psychiatry
DOI 10.17756/jap.2024-045PMC PMC11615735
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Abstract

Objectives: The opioid crisis in the last few decades has mounted to a global level, impacting all areas of socioeconomic, demographic, geographic, and cultural boundaries. Traditional treatments have not been deemed to show the degree of efficacy necessary to address the crisis. The authors of this review paper have set forth an unprecedented and in-depth look into multi-factorial determinants that have contributed to the opioid crisis becoming global and multi-faceted. Methods: For this narrative review/opinion article, we searched PsychINFO, PubMed, Google Scholar, and Web of Science databases to identify relevant articles on topics including the "opioid crisis," "opioid mechanisms," "genetics and epigenetics," "neuropharmacology," and "clinical aspects of opioid treatment and prevention." Since this was not a systematic review the articles selected could represent unitential bias. Results: Despite some success achieved through Opioid Substitution Therapy (OST) in harm reduction, the annual mortality toll in the US alone surpasses 106,699 individuals, a figure expected to climb to 165,000 by 2025. Data from the Substance Abuse and Mental Health Services Administration's (SAMHSA) National Survey on Drug Abuse and Health (NSDUH) reveals that approximately 21.4% of individuals in the US engaged in illicit drug use in 2020, with 40.3 million individuals aged 12 or older experiencing a Substance Use Disorder (SUD). Provisional figures from the Centers for Disease Control and Prevention (CDC) indicate a troubling 15% increase in overdose deaths in 2021, rising from 93,655 in 2020 to 107,622, with opioids accounting for roughly 80,816 of these deaths. Conclusions: We advocate reevaluating the "standard of care" and shifting towards inducing dopamine homeostasis by manipulating key neurotransmitter systems within the brain's reward cascade. We propose a paradigm shift towards a novel "standard of care" that begins with incorporating Genetic Addiction Risk Severity (GARS) testing to assess pre-addiction risk and vulnerability to opioid-induced addiction; emphasis should be placed on inducing dopamine homeostasis through safe and non-addictive alternatives like KB220, and comprehensive treatment approaches that address psychological, spiritual, and societal aspects of addiction through Awareness Integration Therapy (AIT).

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  1. Coffin PO, Maya S, Kahn JG. 2022. Modeling of overdose and naloxone distribution in the setting of fentanyl compared to heroin. Drug Alcohol Depend 236: 109478. 10.1016/ j.drugalcdep.2022.109478 [PubMed: 35588609] · DOI
  2. Dai Z, Abate MA, Groth CP, Rucker T, Kraner JC, et al. 2022. Fentanyl and other opioid involvement in methamphetamine-related deaths. Am J Drug Alcohol Abuse 48(2): 226-234. 10.1080/00952990.2021.1981919 [PubMed: 34752718] · DOI
  3. Blum K, Fried L, Madigan MA, Giordano J, Modestino EJ, et al. 2017. Critical analysis of white house anti-drug plan. Glob J Addict Rehabil Med 1(4): 555568. 10.19080/gjarm.2017.01.555568 [PubMed: 29057394] · DOI
  4. Park JN, Schneider KE, Fowler D, Sherman SG, Mojtabai R, et al. 2022. Polysubstance overdose deaths in the fentanyl era: A latent class analysis. J Addict Med 16(1): 49-55. 10.1097/ adm.0000000000000823 [PubMed: 33675604] · DOI
  5. Mattson CL. 2021. Trends and geographic patterns in drug and synthetic opioid overdose deaths- United States, 2013-2019. Morb Mortal Wkly Rep 70(6): 202-207. 10.15585/mmwr.mm7006a4 · DOI
  6. Nestler EJ. 2001. Molecular neurobiology of addiction. Am J Addict 10(3): 201-217. 10.1080/105504901750532094 [PubMed: 11579619] · DOI
  7. Levitt M, Manson N. 2007. My genes made me do it? The implications of behavioural genetics for responsibility and blame. Health Care Anal 15: 33-40. 10.1007/s10728-006-0038-0 [PubMed: 17373130] · DOI
  8. Blum K, Green R, Mullen P, Han D, Bowirrat A, et al. 2023. Reward Deficiency Syndrome Solution System (RDSSS) a genetically driven putative inducer of "Dopamine Homeostasis" as a futuristic alternative to enhance rehabilitation instead of incarceration. Asian J Complement Altern Med 11(1): 11-14. 10.53043/2347-3894.acam11003 [PubMed: 36865662] · DOI
  9. Caulkins JP, Disley E, Tzvetkova M, Pardal M, Shah H, et al. 2016. Modeling the structure and operation of drug supply chains: the case of cocaine and heroin in Italy and Slovenia. Int J Drug Policy 31: 64-73. 10.1016/j.drugpo.2016.02.003 [PubMed: 26997542] · DOI
  10. Caulkins JP, Reuter P. 2022. How much demand for money laundering services does drug selling create? Identifying the key parameters. Int J Drug Policy 103: 103652. 10.1016/ j.drugpo.2022.103652 [PubMed: 35334339] · DOI
  11. Park JN, Linton SL, Sherman SG, German D. 2019. Police violence among people who inject drugs in Baltimore, Maryland. Int J Drug Policy 64: 54-61. 10.1016/j.drugpo.2018.12.005 [PubMed: 30579221] · DOI
  12. Gold MS, Baron D, Bowirrat A, Blum K. 2020. 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 418: 117137. 10.1016/j.jns.2020.117137 [PubMed: 32957037] · DOI
  13. Modestino EJ, Blum K, Dennen CA, Downs BW, Bagchi D, et al. 2022. Theorizing the role of dopaminergic polymorphic risk alleles with intermittent explosive disorder (IED), violent/ aggressive behavior and addiction: justification of genetic addiction risk severity (GARS) testing. J Pers Med 12(12): 1946. 10.3390/jpm12121946 [PubMed: 36556167] · DOI
  14. Miron J, Partin E. 2021. Ending the war on drugs is an essential step toward racial justice. Am J Bioeth 21(4): 1-3. 10.1080/15265161.2021.1895590 · DOI
  15. Kohler-Hausmann J 2010. " The Attila the Hun Law": New York's Rockefeller drug laws and the making of a punitive state. J Soc Hist 1: 71-95. 10.1353/jsh.2010.0039 · DOI
  16. Gossop M, Trakada K, Stewart D, Witton J. 2005. Reductions in criminal convictions after addiction treatment: 5-year follow-up. Drug Alcohol Depend 79(3): 295-302. 10.1016/ j.drugalcdep.2005.01.023 [PubMed: 16102373] · DOI
  17. Ball SJ, Simpson K, Zhang J, Marsden J, Heidari K, et al. 2021. High-risk opioid prescribing trends: prescription drug monitoring program data from 2010 to 2018. J Public Health Manag Pract 27(4): 379-384. 10.1097/phh.0000000000001203 [PubMed: 32956292] · DOI
  18. Payte JT, Wallace JE, Blum K. Hydrolysis. 1971. A requisite for morphine detection in urine. Curr Ther Res Clin Exp 13(6): 412-416. [PubMed: 4996228]
  19. Blum K, Febo M, Smith DE, Roy III AK, Demetrovics Z, et al. 2015. Neurogenetic and epigenetic correlates of adolescent predisposition to and risk for addictive behaviors as a function of prefrontal cortex dysregulation. J Child Adolesc Psychopharmacol 25(4): 286-292. 10.1089/ cap.2014.0146 [PubMed: 25919973] · DOI
  20. Blum K, Bowirrat A, Lewis MC, Simpatico TA, Ceccanti M, et al. 2021. Exploration of epigenetic state hyperdopaminergia (Surfeit) and genetic trait hypodopaminergia (Deficit) during adolescent brain development. Curr Psychopharmacol 10 (3): 181-196. 10.2174/2211556010666210215155509 · DOI
  21. Salo J, Jokela M, Lehtimäki T, Keltikangas-Järvinen L. 2011. Serotonin receptor 2A gene moderates the effect of childhood maternal nurturance on adulthood social attachment. Genes Brain Behav 10(7): 702-709. 10.1111/j.1601-183x.2011.00708.x [PubMed: 21649857] · DOI
  22. Samochowiec J, Syrek S, Michał P, Ryżewska-Wódecka A, Samochowiec A, et al. 2004. Polymorphisms in the serotonin transporter and monoamine oxidase A genes and their relationship to personality traits measured by the temperament and character inventory and NEO five- factor inventory in healthy volunteers. Neuropsychobiology 50(2): 174-181. 10.1159/000079111 [PubMed: 15292674] · DOI
  23. Bowman GD, Poirier MG. 2014. Post-translational modifications of histones that influence nucleosome dynamics. Chem Rev 115(6): 2274-2295. 10.1021/cr500350x [PubMed: 25424540] · DOI
  24. Haggarty P 2015. Genetic and metabolic determinants of human epigenetic variation. Curr Opin Clin Nutr Metab Care 18(4): 334-338. 10.1097/mco.0000000000000194 [PubMed: 26049630] · DOI
  25. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, et al. 2008. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci 105(44): 17046-17049. 10.1073/pnas.0806560105 [PubMed: 18955703] · DOI · Paper page
  26. Levey DF, Stein MB, Wendt FR, Pathak GA, Zhou H, et al. 2021. Bi-ancestral depression GWAS in the million veteran program and meta-analysis in> 1.2 million individuals highlight new therapeutic directions. Nat Neurosci 24(7): 954-963. 10.1038/s41593-021-00860-2 [PubMed: 34045744] · DOI · Paper page
  27. Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, et al. 1990. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 263(15): 2055-2260. [PubMed: 1969501]
  28. Budhavarapu VN, Chavez M, Tyler JK. 2013. How is epigenetic information maintained through DNA replication?. Epigenetics Chromatin 6: 1-7. 10.1186/1756-8935-6-32 [PubMed: 23289424] · DOI
  29. Law PP, Holland ML. 2019. DNA methylation at the crossroads of gene and environment interactions. Essays Biochem 63(6): 717-726. 10.1042/ebc20190031 [PubMed: 31782496] · DOI
  30. Li CJ. 2013. DNA demethylation pathways: recent insights. Genet Epigenet S12143. 10.4137/ geg.s12143 · DOI
  31. Moore LD, Le T, Fan G. 2013. DNA methylation and its basic function. Neuropsychopharmacol 38(1): 23-38. 10.1038/npp.2012.112 · DOI · Paper page
  32. Mahna D, Puri S, Sharma S. 2018. DNA methylation signatures: biomarkers of drug and alcohol abuse. Mutat Res Rev Mutat Res 777: 19-28. 10.1016/j.mrrev.2018.06.002 [PubMed: 30115428] · DOI
  33. Bogdanović O, Lister R. 2017. DNA methylation and the preservation of cell identity. Curr Opin Genet Dev 46: 9-14. 10.1016/j.gde.2017.06.007 [PubMed: 28651214] · DOI
  34. Sivalingam K, Samikkannu T. 2020. Neuroprotective effect of piracetam against cocaine-induced neuro epigenetic modification of DNA methylation in astrocytes. Brain Sci 10(9): 611. 10.3390/ brainsci10090611 [PubMed: 32899583] · DOI
  35. Kulis M, Esteller M. 2010. DNA methylation and cancer. Adv Genet 70: 27-56. 10.1016/ b978-0-12-380866-0.60002-2 [PubMed: 20920744] · DOI
  36. Dawson MA, Kouzarides T. 2012. Cancer epigenetics: from mechanism to therapy. Cell 150(1): 12-27. 10.1016/j.cell.2012.06.013 [PubMed: 22770212] · DOI · Paper page
  37. Nishiyama A, Nakanishi M. 2021. Navigating the DNA methylation landscape of cancer. Trends Genet 37(11): 1012-1027. 10.1016/j.tig.2021.05.002 [PubMed: 34120771] · DOI
  38. Meng H, Cao Y, Qin J, Song X, Zhang Q, et al. 2015. DNA methylation, its mediators and genome integrity. Int J Biol Sci 11(5): 604-617. 10.7150/ijbs.11218 [PubMed: 25892967] · DOI
  39. Bajrami E, Spiroski M. 2016. Genomic imprinting. Open Access Maced J Med Sci 4(1): 181-184. 10.3889/oamjms.2016.028 [PubMed: 27275355] · DOI
  40. Cassidy SB, Schwartz S. 1998. Prader-Willi and Angelman syndromes: disorders of genomic imprinting. Medicine. 77(2): 140-151. 10.1097/00005792-199803000-00005 [PubMed: 9556704] · DOI
  41. Liu C, Jiao C, Wang K, Yuan N. 2018. DNA methylation and psychiatric disorders. Prog Mol Biol Transl Sci 157: 175-232. 10.1016/bs.pmbts.2018.01.006 [PubMed: 29933950] · DOI
  42. Tessarz P, Kouzarides T. 2014. Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol 15(11): 703-708. 10.1038/nrm3890 [PubMed: 25315270] · DOI · Paper page
  43. Stillman B 2018. Histone modifications: insights into their influence on gene expression. Cell 175(1): 6-9. 10.1016/j.cell.2018.08.032 [PubMed: 30217360] · DOI
  44. Zhao Z, Shilatifard A. 2019. Epigenetic modifications of histones in cancer. Genome Biol 20: 1-6. 10.1186/s13059-019-1870-5 [PubMed: 30606230] · DOI
  45. Hyland EM, Cosgrove MS, Molina H, Wang D, Pandey A, et al. 2005. Insights into the role of histone H3 and histone H4 core modifiable residues in Saccharomyces cerevisiae. Mol Cell Biol 25(22): 10060-10070. 10.1128/mcb.25.22.10060-10070.2005 [PubMed: 16260619] · DOI
  46. Kim S, Kaang BK. 2017. Epigenetic regulation and chromatin remodeling in learning and memory. Exp Mol Med 49(1): e281. 10.1038/emm.2016.140 [PubMed: 28082740] · DOI
  47. Clapier CR, Cairns BR. 2009. The biology of chromatin remodeling complexes. Annu Rev Biochem 78: 273-304. 10.1146/annurev.biochem.77.062706.153223 [PubMed: 19355820] · DOI
  48. Han P, Hang CT, Yang J, Chang CP. 2011. Chromatin remodeling in cardiovascular development and physiology. Circ Res 108(3): 378-396. 10.1161/circresaha.110.224287 [PubMed: 21293009] · DOI
  49. Ko MS. 2016. Zygotic genome activation revisited: looking through the expression and function of Zscan4. Curr Top Dev Biol 120: 103-124. 10.1016/bs.ctdb.2016.04.004 [PubMed: 27475850] · DOI
  50. Wall AE, Kohl PL. 2007. Substance use in maltreated youth: findings from the national survey of child and adolescent well-being. Child Maltreat 12(1): 20-30. 10.1177/1077559506296316 [PubMed: 17218645] · DOI
  51. Dackis MN, Rogosch FA, Cicchetti D. 2015. Child maltreatment, callous-unemotional traits, and defensive responding in high-risk children: an investigation of emotion-modulated startle response. Dev Psychopathol 27: 1527-1545 10.1017/s0954579415000929 [PubMed: 26535942] · DOI
  52. Sutherland MT, McHugh MJ, Pariyadath V, Stein EA. 2012. Resting state functional connectivity in addiction: lessons learned and a road ahead. Neuroimage 62(4): 2281-2295. 10.1016/ j.neuroimage.2012.01.117 [PubMed: 22326834] · DOI
  53. Blum K, Green R, Smith J, Llanos-Gomez L, Baron D, et al. 2020. Hypothesizing high negative emotionality as a function of genetic addiction risk severity (GARS) testing in alcohol use disorder (AUD). J Syst Integr Neurosci 7: 1-3. 10.15761/jsin.1000245 · DOI
  54. Haggarty P, Ferguson-Smith AC. 2014. Life Course Epigenetics and Healthy Aging. In Kuh D, Cooper R, Hardy R, Richards M, Ben-Shlomo Y (eds) A Life Course Approach to Healthy Aging. Oxford University Press, London, pp 198-212.
  55. Tiffon C 2018. The impact of nutrition and environmental epigenetics on human health and disease. Int J Mol Sci 19(11): 3425. 10.3390/ijms19113425 [PubMed: 30388784] · DOI
  56. Bava S, Tapert SF. 2010. Adolescent brain development and the risk for alcohol and other drug problems. Neuropsychol Rev 20: 398-413. 10.1007/s11065-010-9146-6 [PubMed: 20953990] · DOI
  57. Uhart M, Wand GS. 2009. Stress, alcohol and drug interaction: an update of human research. Addict Biol 14(1): 43-64. 10.1111/j.1369-1600.2008.00131.x [PubMed: 18855803] · DOI
  58. Blum K, Chen AL, Oscar-Berman M, Chen TJ, Lubar J, et al. 2011. Generational association studies of dopaminergic genes in reward deficiency syndrome (RDS) subjects: selecting appropriate phenotypes for reward dependence behaviors. Int J Environ Res Public Health 8(12): 4425-4459. 10.3390/ijerph8124425 [PubMed: 22408582] · DOI
  59. Fowler JH, Settle JE, Christakis NA. 2011. Correlated genotypes in friendship networks. Proc Nat Acad Sci 108(5): 1993-1997. 10.1073/pnas.1011687108 [PubMed: 21245293] · DOI · Paper page
  60. Blum K, Oscar-Berman M, Bowirrat A, Giordano J, Madigan M, et al. 2012. Neuropsychiatric genetics of happiness, friendships, and politics: hypothesizing homophily ("birds of a feather flock together") as a function of reward gene polymorphisms. J Genet Syndr Gene Ther 3(112): 1-8. 10.4172/2157-7412.1000112 · DOI
  61. Andersen SL, Teicher MH. 2009. Desperately driven and no brakes: developmental stress exposure and subsequent risk for substance abuse. Neurosci Biobehav Rev 33(4): 516-524. 10.1016/ j.neubiorev.2008.09.009 [PubMed: 18938197] · DOI · Paper page
  62. Pfefferbaum A, Mathalon DH, Sullivan EV, Rawles JM, Zipursky RB, et al. 1994. A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol 51(9): 874-887. 10.1001/archneur.1994.00540210046012 [PubMed: 8080387] · DOI · Paper page
  63. Giedd JN, Rumsey JM, Castellanos FX, Rajapakse JC, Kaysen D, et al. 1996. A quantitative MRI study of the corpus callosum in children and adolescents. Dev Brain Res 91(2): 274-280. 10.1016/0165-3806(95)00193-x [PubMed: 8852379] · DOI
  64. Spear L 2000. Modeling adolescent development and alcohol use in animals. Alcohol Res Health 24(2): 115-123. [PubMed: 11199278]
  65. Yurgelun-Todd DA, Killgore WD, Young AD. 2002. Sex differences in cerebral tissue volume and cognitive performance during adolescence. Psychol Rep 91(3): 743-757. 10.2466/ pr0.2002.91.3.743 [PubMed: 12530718] · DOI
  66. Melo P, Moreno VZ, Vázquez SP, Pinazo-Durán MD, Tavares MA. 2006. Myelination changes in the rat optic nerve after prenatal exposure to methamphetamine. Brain Res 1106(1): 21-29. 10.1016/j.brainres.2006.05.020 [PubMed: 16842764] · DOI
  67. Xu J, Yang B, Yan C, Hu H, Cai S, et al. 2013. Effects of duration and timing of prenatal stress on hippocampal myelination and synaptophysin expression. Brain Res 1527: 57-66. 10.1016/ j.brainres.2013.06.025 [PubMed: 23806778] · DOI
  68. De Bellis MD, Narasimhan A, Thatcher DL, Keshavan MS, Soloff P, et al. 2005. Prefrontal cortex, thalamus, and cerebellar volumes in adolescents and young adults with adolescent-onset alcohol use disorders and comorbid mental disorders. Alcohol Clin Exp Res 29(9): 1590-1600. 10.1097/01.alc.0000179368.87886.76 [PubMed: 16205359] · DOI · Paper page
  69. Whitesell M, Bachand A, Peel J, Brown M. 2013. Familial, social, and individual factors contributing to risk for adolescent substance use. J Addict 2013: 1-9. 10.1155/2013/579310 · DOI
  70. Gold MS, Redmond JRDE, Kleber HD. 1978. Clonidine in opiate withdrawal. Lancet 311(8070): 929-930. 10.1016/s0140-6736(78)90699-2 · DOI
  71. Verebey K, Blum K. 1979. Alcohol euphoria: possible mediation via endorphinergic mechanisms. J Psychedelic Drugs 11(4): 305-311. 10.1080/02791072.1979.10471413 [PubMed: 230360] · DOI
  72. Blum K, Topel H. 1986. Opioid peptides and alcoholism: genetic deficiency and chemical management. Funct Neurol 1(1): 71-83. [PubMed: 2956168]
  73. Blum K, Briggs AH, Elston SF, DeLallo L. 1980. Psychogenetics of drug seeking behavior. Subst Alcohol Actions Misuse 1(3): 255-257. [PubMed: 7347918]
  74. Gold MS, Donabedian RK, Redmond DE Jr. 1978. Clonidine-induced increase in serum growth hormone: possible role of epinephrine-mediated synapses. Psychoneuroendocrinology 3(2): 187- 194. 10.1016/0306-4530(78)90007-0 [PubMed: 212772] · DOI
  75. Gold MS, Kleber HD. 1979. A rationale for opiate withdrawal symptomatology. Drug Alcohol Depend 4(5): 419-424. 10.1016/0376-8716(79)90074-7 [PubMed: 228923] · DOI
  76. Gold MS, Byck R, Sweeney DR, Kleber HD. 1979. Endorphin-locus coeruleus connection mediates opiate action and withdrawal. Biomedicine 30(1): 1-4. [PubMed: 223678]
  77. Blum K, Wallace JE, Schwerter HA, Eubanks JD. 1976. Morphine suppression of ethanol withdrawal in mice. Experientia 32: 79-82. 10.1007/bf01932634 [PubMed: 942927] · DOI
  78. Blum K, Futterman S, Wallace JE, Schwertner HA. 1977. Naloxone-induced inhibition of ethanol dependence in mice. Nature 265(5589): 49-51. 10.1038/265049a0 [PubMed: 556802] · DOI
  79. Blum K, Hamilton MG, Hirst M, Wallace JE. 1978. Putative role of isoquinoline alkaloids in alcoholism: a link to opiates. Alcohol Clin Exp Res 2(2): 113-120. 10.1111/ j.1530-0277.1978.tb04710.x [PubMed: 350073] · DOI
  80. Blum K, Eubanks JD, Wallace JE, Schwertner HA. 1976. Suppression of ethanol withdrawal by dopamine. Experientia 32(4): 493-495. 10.1007/bf01920816 [PubMed: 944645] · DOI · Paper page
  81. Blum K, Hamilton M, Meyer E, Hirst M, Marshall A. 1977. Isoquinoline alkaloids as possible regulators of alcohol addiction. Lancet 309(8015): 799-800. 10.1016/s0140-6736(77)92981-6 · DOI
  82. Kaufling J, Aston-Jones G. 2015. Persistent adaptations in afferents to ventral tegmental dopamine neurons after opiate withdrawal. J Neurosci 35(28): 10290-10303. 10.1523/ jneurosci.0715-15.2015 [PubMed: 26180204] · DOI
  83. Di Chiara G, Imperato A. 1988. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natal Acad Sci 85(14): 5274-5278. 10.1073/pnas.85.14.5274 100. · DOI
  84. Gipson CD, Kupchik YM, Kalivas PW. 2014. Rapid, transient synaptic plasticity in addiction. Neuropharmacol 76: 276-286. 10.1016/j.neuropharm.2013.04.032 101. · DOI
  85. George O, Le Moal M, Koob GF. 2012. Allostasis and addiction: role of the dopamine and corticotropin-releasing factor systems. Physiol Behav 106(1): 58-64. 10.1016/ j.physbeh.2011.11.004 [PubMed: 22108506] 102. · DOI · Paper page
  86. Rasakham K, Schmidt HD, Kay K, Huizenga MN, Calcagno N, et al. 2014. Synapse density and dendritic complexity are reduced in the prefrontal cortex following seven days of forced abstinence from cocaine self-administration. PLoS One 9(7): e102524. 10.1371/ journal.pone.0102524 [PubMed: 25072653] 103. · DOI
  87. Blum K, Badgaiyan RD, Gold MS. 2015. Hypersexuality addiction and withdrawal: phenomenology, neurogenetics and epigenetics. Cureus 7(10): e348. 10.7759/cureus.348 [PubMed: 26623203] 104. Nestler EJ. 2014. Epigenetic mechanisms of drug addiction. Neuropharmacol 76: 259-268. 10.1016/j.conb.2013.01.001 105. Nestler EJ. 2013. Cellular basis of memory for addiction. Dialogues Clin Neurosci 15(4): 431- 443. 10.31887/dcns.2013.15.4/enestler [PubMed: 24459410] 106. · DOI
  88. Renthal W, Nestler EJ. 2008. Epigenetic mechanisms in drug addiction. Trends Mol Med 14(8): 341-350. 10.1016/j.molmed.2008.06.004 [PubMed: 18635399] 107. · DOI
  89. Robison AJ, Nestler EJ. 2011. Transcriptional and epigenetic mechanisms of addiction. Nat Rev Neurosci 12(11): 623-637. 10.1038/nrn3111 [PubMed: 21989194] 108. · DOI · Paper page
  90. Sadri-Vakili G, Kumaresan V, Schmidt HD, Famous KR, Chawla P, et al. 2010. Cocaine-induced chromatin remodeling increases brain-derived neurotrophic factor transcription in the rat medial prefrontal cortex, which alters the reinforcing efficacy of cocaine. J Neurosci 30(35): 11735- 11744. 10.1523/jneurosci.2328-10.2010 [PubMed: 20810894] 109. · DOI
  91. Szutorisz H, Hurd YL. 2016. Epigenetic effects of cannabis exposure. Biol Psychiatry 79(7): 586-594. 10.1016/j.biopsych.2015.09.014 [PubMed: 26546076] 110. · DOI
  92. Lee BR, Ma YY, Huang YH, Wang X, Otaka M, et al. 2013. Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving. Nat Neurosci 16(11): 1644-1651. 10.1038/nn.3533 [PubMed: 24077564] 112. · DOI
  93. Zou F, Wu X, Zhai T, Lei Y, Shao Y, et al. 2015. Abnormal resting-state functional connectivity of the nucleus accumbens in multi-year abstinent heroin addicts. J Neurosci Res 93(11): 1693-1702. 10.1002/jnr.23608 [PubMed: 26280556] 118. · DOI
  94. Blum K, Gold MS, Jacobs W, McCall WV, Febo M, et al. 2017. Neurogenetics of acute and chronic opiate/opioid abstinence: treating symptoms and the cause. Front Biosci 22: 1247-1288. 10.2741/4544 119. · DOI
  95. Gondré-Lewis MC, Elman I, Alim T, Chapman E, Settles-Reaves B, et al. 2022. Frequency of the dopamine receptor D3 (rs6280) vs. opioid receptor μ1 (rs1799971) polymorphic risk alleles in patients with opioid use disorder: a preponderance of dopaminergic mechanisms?. Biomedicines 10(4): 870. 10.3390/biomedicines10040870 [PubMed: 35453620] 120. · DOI
  96. Schmeichel BE, Barbier E, Misra KK, Contet C, Schlosburg JE, et al. 2015. Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats. Neuropsychopharmacology 40(5): 1123-1129. 10.1038/npp.2014.293 [PubMed: 25367502] 121. · DOI · Paper page
  97. Peciña M, Love T, Stohler CS, Goldman D, Zubieta JK. 2015. Effects of the Mu opioid receptor polymorphism (OPRM1 A118G) on pain regulation, placebo effects and associated personality trait measures. Neuropsychopharmacology 40(4): 957-965. 10.1038/npp.2014.272 [PubMed: 25308352] 122. Lutz PE, Ayranci G, Chu-Sin-Chung P, Matifas A, Koebel P, et al. 2014. Distinct mu, delta, and kappa opioid receptor mechanisms underlie low sociability and depressive-like behaviors during heroin abstinence. Neuropsychopharmacology 39(11): 2694-2705. 10.1038/npp.2014.126 [PubMed: 24874714] 123. · DOI
  98. Pan J, Yu J, Sun L, Xie C, Chang L, et al. 2019. ALDH1A1 regulates postsynaptic μ-opioid receptor expression in dorsal striatal projection neurons and mitigates dyskinesia through transsynaptic retinoic acid signaling. Sci Rep 9(1): 3602. 10.1038/s41598-019-40326-x [PubMed: 30837649] 124. Schwantes-An TH, Zhang J, Chen LS, Hartz SM, Culverhouse RC, et al. 2016. Association of the OPRM1 variant rs1799971 (A118G) with non-specific liability to substance dependence in a collaborative de novo meta-analysis of European-ancestry cohorts. Behav Genet 46: 151-169. 10.1007/s10519-015-9737-3 [PubMed: 26392368] 125. · DOI
  99. Lovallo WR, Enoch MA, Acheson A, Cohoon AJ, Sorocco KH, et al. 2015. Cortisol stress response in men and women modulated differentially by the mu-opioid receptor gene polymorphism OPRM1 A118G. Neuropsychopharmacology 40(11): 2546-2554. 10.1038/ npp.2015.101 [PubMed: 25881118] 126. · DOI
  100. Baehr C, Robinson C, Kassick A, Jahan R, Gradinati V, et al. 2022. Preclinical efficacy and selectivity of vaccines targeting fentanyl, alfentanil, sufentanil, and acetylfentanyl in rats. ACS Omega 7(19): 16584-16592. 10.1021/acsomega.2c00820 [PubMed: 35601290] 127. Substance Abuse and Mental Health Services Administration (US); Office of the Surgeon General (US). 2016. Facing addiction in America: The Surgeon General's Report on Alcohol, Drugs, and Health. Reports of the Surgeon General. Washington, DC: US Department of Health and Human Service. 128. Koob GF. 1996. Hedonic valence, dopamine and motivation. Mol Psychiatry 1(3): 186-189. [PubMed: 9118342] 129. · DOI
  101. Blum K, Febo M, McLaughlin T, Cronje FJ, Han D, et al. 2014. Hatching the behavioral addiction egg: reward deficiency solution system (RDSS) ™ as a function of dopaminergic neurogenetics and brain functional connectivity linking all addictions under a common rubric. J Behav Addict 3(3): 149-156. 10.1556/jba.3.2014.019 [PubMed: 25317338] 130. · DOI
  102. Borsook D, Linnman C, Faria V, Strassman AM, Becerra L, et al. 2016. Reward deficiency and anti-reward in pain chronification. Neurosci Biobehav Rev 68: 282-297. 10.1016/ j.neubiorev.2016.05.033 [PubMed: 27246519] 131. · DOI
  103. Olney JJ, Warlow SM, Naffziger EE, Berridge KC. 2018. Current perspectives on incentive salience and applications to clinical disorders. Cur Opin Behav Sci 22: 59-69. 10.1016/ j.cobeha.2018.01.007 133. · DOI
  104. Blum K, Siwicki D, Baron D, Modestino EJ, Badgaiyan RD. 2018. The benefits of genetic addiction risk score (GARS ™ ) and pro-dopamine regulation in combating suicide in the American Indian population. J Syst Integr Neurosci 9(4): 1-6. 10.15761/jsin.1000195 134. Blum K, Gondré-Lewis M, Steinberg B, Elman I, Baron D, et al. 2018. Our evolved unique pleasure circuit makes humans different from apes: reconsideration of data derived from animal studies. J Syst Integ Neurosci 4(1): 1-7. 10.15761/jsin.1000191 135. · DOI
  105. Blum K, Gardner E, Oscar-Berman M, Gold M. 2012. "Liking" and "wanting" linked to reward deficiency syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry. Curr Pharm Des 18(1): 113-118. 10.2174/138161212798919110 [PubMed: 22236117] 136. · DOI · Paper page
  106. Davis CA, Levitan RD, Reid C, Carter JC, Kaplan AS, et al. 2009. Dopamine for "wanting" and opioids for "liking": a comparison of obese adults with and without binge eating. Obesity 17(6): 1220-1225. 10.1038/oby.2009.52 [PubMed: 19282821] 137. · DOI · Paper page
  107. File D, Bőthe B, File B, Demetrovics Z. 2022. The role of impulsivity and reward deficiency in "liking" and "wanting" of potentially problematic behaviors and substance uses. Front Psychiatry 13: 820836. 10.3389/fpsyt.2022.820836 [PubMed: 35546934] 138. · DOI
  108. Lewis M 2018. Brain change in addiction as learning, not disease. N Engl J Med 379(16): 1551- 1560. 10.1056/nejmra1602872 [PubMed: 30332573] 140. · DOI
  109. Compton WM, Wargo EM, Volkow ND. 2022. Neuropsychiatric model of addiction simplified. Psychiatr Clin 45(3): 321-334. 10.1016/j.psc.2022.05.001 141. Early Brain Development and Epigenetics. In Center on the Developing Child at Harvard University. 142. · DOI
  110. Hamilton PJ, Nestler EJ. 2019. Epigenetics and addiction. Curr Opin Neurobiol 59: 128-136. 10.1016/j.conb.2019.05.005 [PubMed: 31255844] 143. · DOI · Paper page
  111. Allis CD, Jenuwein T. 2016. The molecular hallmarks of epigenetic control. Nat Rev Genet 17(8): 487-500. 10.1038/nrg.2016.59 [PubMed: 27346641] 144. · DOI · Paper page
  112. Blum K, Gold MS, Cadet JL, Baron D, Bowirrat A, et al. 2022. Dopaminylation in psychostimulant use disorder protects against psychostimulant seeking behavior by normalizing nucleus accumbens (NAc) dopamine expression. Curr Psychopharmacol 11(1): 11-17. 10.2174/2211556009666210108112737 [PubMed: 36046837] 145. · DOI
  113. Bannister AJ, Kouzarides T. 2011. Regulation of chromatin by histone modifications. Cell Res 21(3): 381-395. 10.1038/cr.2011.22 [PubMed: 21321607] 146. · DOI · Paper page
  114. Archer T, Oscar-Berman M, Blum K, Gold MS. 2013. Epigenetic modulation of mood disorders. J Genet Syndr Gene Ther 4(120): 1000120. 10.4172/2157-7412.1000120 [PubMed: 23565345] 147. · DOI
  115. Rogge GA, Wood MA. 2013. The role of histone acetylation in cocaine-induced neural plasticity and behavior. Neuropsychopharmacology 38(1): 94-110. 10.1038/npp.2012.154 [PubMed: 22910457] 148. · DOI
  116. Egervari G, Ciccocioppo R, Jentsch JD, Hurd YL. 2018. Shaping vulnerability to addiction-the contribution of behavior, neural circuits and molecular mechanisms. Neurosci Biobehav Rev 85: 117-125. 10.1016/j.neubiorev.2017.05.019 [PubMed: 28571877] 149. J Kennedy P, Harvey E. 2015. Histone deacetylases as potential targets for cocaine addiction. CNS Neurol Disord Drug Targets 14(6): 764-772. 10.2174/1871527314666150529144804 [PubMed: 26022264] 150. · DOI
  117. Ceccanti M, Blum K, Bowirrat A, Dennen CA, Braverman ER, et al. 2022. Future newborns with opioid-induced neonatal abstinence syndrome (NAS) could be assessed with the genetic addiction risk severity (GARS) test and potentially treated using precision amino-acid enkephalinase inhibition therapy (KB220) as a frontline modality instead of potent opioids. J Pers Med 12(12): 2015. 10.3390/jpm12122015 [PubMed: 36556236] 151. Zhang J, Fan Y, Zhou J, Ma T, Gao K, et al. 2021. Methylation quantitative trait locus rs5326 is associated with susceptibility and effective dosage of methadone maintenance treatment for heroin use disorder. Psychopharmacology 238(12): 3511-3518. 10.1007/s00213-021-05968-8 [PubMed: 34476566] 152. · DOI
  118. Blum K, Baron D, Lott L, Ponce JV, Siwicki D, et al. 2020. In search of reward deficiency syndrome (RDS)-free controls: the "holy grail" in genetic addiction risk testing. Curr Psychopharmacol 9(1): 7-21. [PubMed: 32432025] 153.
  119. Browne CJ, Godino A, Salery M, Nestler EJ. 2020. Epigenetic mechanisms of opioid addiction. Biol Psychiatry 87(1): 22-33. 10.1016/j.biopsych.2019.06.027 [PubMed: 31477236] 154. Kreek MJ, Levran O, Reed B, Schlussman SD, Zhou Y, et al. 2012. Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics. J Clin Invest 122(10): 3387-3393. 10.1172/jci60390 [PubMed: 23023708] 155. · DOI
  120. Cadet JL, Jayanthi S. 2021. Epigenetics of addiction. Neurochem Int 147: 105069. 10.1016/ j.neuint.2021.105069 [PubMed: 33992741] 156. · DOI
  121. Crist RC, Reiner BC, Berrettini WH. 2019. A review of opioid addiction genetics. Curr Opin Psychol 27: 31-35. 10.1016/j.copsyc.2018.07.014 [PubMed: 30118972] 157. · DOI
  122. Nazmara Z, Shirinbayan P, Reza Asgari H, Ahadi R, Asgari F, et al. 2021. The epigenetic alterations of human sperm cells caused by heroin use disorder. Andrologia 53(1): e13799. 10.1111/and.13799 [PubMed: 33099803] 158. Zhang J, Fu X, Lu Y, Cheng C, Wang K, et al. 2022. Hypermethylation in the promoter region of the ADRA1A gene is associated with opioid use disorder in Han Chinese. Brain Res 1793: 148050. 10.1016/j.brainres.2022.148050 [PubMed: 35964682] 159. · DOI
  123. Corradin O, Sallari R, Hoang AT, Kassim BS, Ben Hutta G, et al. 2022. Convergence of case-specific epigenetic alterations identify a confluence of genetic vulnerabilities tied to opioid overdose. Mol Psychiatry 27(4): 2158-2170. 10.1038/s41380-022-01477-y [PubMed: 35301427] 160. · DOI
  124. Li Y, Lu Y, Xie Q, Zeng X, Zhang R, et al. 2022. Methylation and expression quantitative trait locus rs6296 in the HTR1B gene is associated with susceptibility to opioid use disorder. Psychopharmacology 239(8): 2515-2523. 10.1007/s00213-022-06141-5 [PubMed: 35438303] 161. · DOI
  125. Gilbert PA, Drabble L, Daniel-Ulloa J, Trocki KF. 2017. Alcohol outcomes by sexual orientation and race/ethnicity: few findings of higher risk. J Stud Alcohol Drugs 78(3): 406-414. 10.15288/ jsad.2017.78.406 [PubMed: 28499108] 165. · DOI
  126. Blum K, Oscar-Berman M, Jacobs W, McLaughlin T, Gold MS. 2014. Buprenorphine response as a function of neurogenetic polymorphic antecedents: can dopamine genes affect clinical outcomes in reward deficiency syndrome (RDS)?. J Addict Res Ther 5. 10.4172/2155-6105.1000185 166. Beauvais P 1996. Trends in drug use among American Indian students and dropouts, 1975 to 1994. Am J Public Health 86(11): 1594-1598. 10.2105/ajph.86.11.1594 [PubMed: 8916526] 167. Damez-Werno DM, Sun H, Scobie KN, Shao N, Rabkin J, et al. 2016. Histone arginine methylation in cocaine action in the nucleus accumbens. Proc Natl Acad Sci 113(34): 9623- 9628. 10.1073/pnas.1605045113 [PubMed: 27506785] 168. Lepack AE, Werner CT, Stewart AF, Fulton SL, Zhong P, et al. 2020. Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking. Science 368(6487): 197-201. 10.1126/ science.aaw8806 [PubMed: 32273471] 169. · DOI
  127. Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ. 1991. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism or gene ism. Arch Gen Psychiatry 48(7): 648-654. 10.1001/archpsyc.1991.01810310066012 [PubMed: 2069496] 170. · DOI · Paper page
  128. Blum K, Mullen PM, Green R. Determinism v. 2021.Free will and genetic evidence of addiction in plea bargaining and sentence mitigation: conversion of incarceration to probation and rehabilitation based on genetic addiction risk severity (GARS) test. Mary's LJ 53: 1055. 171. Kjaer TW, Bertelsen C, Piccini P, Brooks D, Alving J, et al. 2002. Increased dopamine tone during meditation-induced change of consciousness. Cogn Brain Res 13(2): 255-259. 10.1016/ s0926-6410(01)00106-9 172. · DOI
  129. Bogdan R, Hatoum AS, Johnson EC, Agrawal A. 2023. The genetically informed neurobiology of addiction (GINA) model. Nat Re Neurosci 24(1): 40-57. 10.1038/s41583-022-00656-8 173. · DOI
  130. Hodge CW, Cox AA. 1998. The discriminative stimulus effects of ethanol are mediated by NMDA and GABAA receptors in specific limbic brain regions. Psychopharmacology 139: 95- 107. 10.1007/s002130050694 [PubMed: 9768547] 177. · DOI
  131. McKnight ER, Gardner SM, Cottrill AC, Levy CB, Bonny AE. 2023. Trauma and resilience in adolescents and young adults with opioid use and eating disorders. Clin Pediatr 62(8): 856-861. 10.1177/00099228231181742 178. · DOI
  132. Williams JR, Girdler S, Williams W, Cromeens MG. 2021. The effects of co-occurring interpersonal trauma and gender on opioid use and misuse. J Interpers Violence 36(23-24): NP13185-205. 10.1177/0886260519900309 [PubMed: 32054388] 179. von Oelreich E, Eriksson M, Brattström O, Sjölund KF, Discacciati A, et al. 2020. Risk factors and outcomes of chronic opioid use following trauma. J Br Surg 107(4): 413-421. 10.1002/ bjs.11507 180. · DOI
  133. Zvolensky MJ, Rogers AH, Shepherd JM, Vujanovic AA, Bakhshaie J. 2020. Anxiety sensitivity and opioid misuse and dependence among trauma-exposed adults with chronic pain. J Behav Med 43: 174-184. 10.1007/s10865-020-00142-5 [PubMed: 32072365] 181. · DOI
  134. Harmon L, Sukri L, Kufera JA, Nguyen A, Grunnagle M, et al. 2019. Is opioid prescribing driving trauma recidivism or is trauma driving opioid use?. Am Surg 85(6): 567-571. [PubMed: 31267895] 182. Austin AE, Short NA. 2020. Sexual violence, mental health, and prescription opioid use and misuse. Am J Prev Med 59(6): 818-827. 10.1016/j.amepre.2020.06.019 [PubMed: 33220753] 183. · DOI
  135. Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, et al. 2012. Sex, drugs, and rock 'n'roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms. J Psychoactive Drugs 44(1): 38-55. 10.1080/02791072.2012.662112 [PubMed: 22641964] 184. · DOI
  136. Symons FJ, Thompson A, Rodriguez MC. 2004. Self-injurious behavior and the efficacy of naltrexone treatment: a quantitative synthesis. Ment Retard Dev Disabil Res Res 10(3): 193-200. 10.1002/mrdd.20031 185. · DOI
  137. Menon S, Lea RA, Roy B, Hanna M, Wee S, et al. 2012. The human μ-opioid receptor gene polymorphism (A118G) is associated with head pain severity in a clinical cohort of female migraine with aura patients. J Headache Pain 13: 513-519. 10.1007/s10194-012-0468-z [PubMed: 22752568] 188. · DOI
  138. Way BM, Taylor SE, Eisenberger NI. 2009. Variation in the μ-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection. Proc Natl Acad Sci 106(35): 15079-15084. 10.1073/pnas.0812612106 [PubMed: 19706472] 189. Gabor Mate. In The Realm of Hungry Ghosts -Introduction: Hungry Ghosts: The Realm of Addiction. 190. Van der Kolk BA. 1989. The compulsion to repeat the trauma: re-enactment, revictimization, and masochism. Psychiatr Clin North Am 12(2): 389-411. [PubMed: 2664732] 191. · DOI · Paper page
  139. Sagrera CE, Alderman L, Vest MF, Goeders NE, Murnane KS. 2023. Elucidating the role of trauma and significant life stress in the disease of addiction may provide new targets for medication development. CNS Neurol Disord Drug Targets 22(7): 946-949. 10.2174/1871527321666220511145230 [PubMed: 35546748] 192. · DOI
  140. Herron JL, Venner KL. 2023. A systematic review of trauma and substance use in American Indian and Alaska Native individuals: incorporating cultural considerations. J Racial Ethn Health Disparities 10(2): 603-632. 10.1007/s40615-022-01250-5 [PubMed: 35089579] 193. · DOI
  141. Johnson F Jr, RedCloud A, Mootz J, Hallgren KA, Elliott K, et al. 2023. Community member perspectives on adapting the cascade of care for opioid use disorder for a tribal nation in the United States. Addiction 118(8): 1540-1508. 10.1111/add.16184 [PubMed: 36905290] 194. US Department of Veteran Affairs National Center for PTSD. History of PTSD. 195. · DOI
  142. Janet G. Travell, MD: a daughter's recollection. Tex Heart Inst J 30(1): 8-12. [PubMed: 12638664] 196.
  143. White LW, Travell JG. Janet G. Travell, MD, on Myofascial Pain. Journal of Clinical Orthodontics. 197. Levine Peter A. Humans rarely die from trauma. 198.
  144. Blum K, Gold M, Modestino EJ, Baron D, Boyett B, et al. 2018. Would induction of dopamine homeostasis via coupling genetic addiction risk score (GARS ® ) and pro-dopamine regulation benefit benzodiazepine use disorder (BUD)?. J Sys Integr Neurosci 4(2): 1-6. 10.15761/jsin.1000196 199. · DOI
  145. Ahmadi-Soleimani SM, Azizi H, Abbasi-Mazar A. 2021. Intermittent REM sleep deprivation attenuates the development of morphine tolerance and dependence in male rats. Neurosci Lett 748: 135735. 10.1016/j.neulet.2021.135735 [PubMed: 33592307] 200. · DOI
  146. Plaza-Zabala A, Maldonado R, Berrendero F. 2012. The hypocretin/orexin system: implications for drug reward and relapse. Mol Neurobiol 45: 424-439. 10.1007/s12035-012-8255-z [PubMed: 22430644] 201. Steiner MA, Lecourt H, Jenck F. 2013. The dual orexin receptor antagonist almorexant, alone and in combination with morphine, cocaine and amphetamine, on conditioned place preference and locomotor sensitization in the rat. Int J Neuropsychopharmacol 16(2): 417-432. 10.1017/ s1461145712000193 [PubMed: 22436395] 202. · DOI
  147. Kreeger L, Duncan A, Cowap J. 1996. Psychostimulants used for opioid-induced drowsiness. J Pain Symptom Manag 11(1): 1-2. 10.1016/s0885-3924(96)90004-4 203. · DOI
  148. Blum K, Oscar-Berman M, Badgaiyan RD, Khurshid KA, Gold MS. 2014. Dopaminergic neurogenetics of sleep disorders in reward deficiency syndrome (RDS). J Sleep Disorders Ther 3(2): 126. 10.4172/2167-0277.1000e126 204. · DOI
  149. Curtis AF, Miller MB, Rathinakumar H, Robinson M, Staud R, et al. 2019. Opioid use, pain intensity, age, and sleep architecture in patients with fibromyalgia and insomnia. Pain 160(9): 2086-2092. 10.1097/j.pain.0000000000001600 [PubMed: 31180977] 205. · DOI
  150. Blum K, Oscar-Berman M, Badgaiyan R, Braverman ER, Gold MS. 2014. Hypothesizing darkness induced alcohol intake linked to dopaminergic regulation of brain function. Psychology (Irvine) 5(4): 282-288. 10.4236/psych.2014.54038 [PubMed: 25009759] 206. · DOI
  151. Nettleton S, Neale J, Pickering L. 2011. Techniques and transitions: a sociological analysis of sleeping practices amongst recovering heroin users. Soc Sci Med 72(8): 1367-1373. 10.1016/ j.socscimed.2011.02.040 [PubMed: 21458902] 207. · DOI
  152. Xue T, Wu X, Chen S, Yang Y, Yan Z, et al. 2022. The efficacy and safety of dual orexin receptor antagonists in primary insomnia: a systematic review and network meta-analysis. Sleep Med Rev 61: 101573. 10.1016/j.smrv.2021.101573 [PubMed: 34902823] 208. · DOI
  153. Pud D, Zlotnick C, Lawental E. 2012. Pain depression and sleep disorders among methadone maintenance treatment patients. Addict Behav 37(11): 1205-1210. 10.1016/j.addbeh.2012.05.025 [PubMed: 22742985] 209. · DOI
  154. Reyes-Vázquez C, Prieto-Gómez B, Dafny N. 2012. Interferon modulates central nervous system function. Brain Res 1442: 76-89. 10.1016/j.brainres.2011.09.061 [PubMed: 22322149] 210. Mogil JS, Marek P, Flodman P, Spence MA, Sternberg WF, et al. 1995. One or two genetic loci mediate high opiate analgesia in selectively bred mice. Pain 60(2): 125-135. 10.1016/0304-3959(94)00098-y [PubMed: 7784097] 211. · DOI
  155. Coller JK, Barratt DT, Dahlen K, Loennechen MH, Somogyi AA. 2006. ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals. Clin Pharmacol Ther 80(6): 682-690. 10.1016/j.clpt.2006.09.011 [PubMed: 17178268] 212. · DOI
  156. McClung CA, Nestler EJ, Zachariou V. 2005. Regulation of gene expression by chronic morphine and morphine withdrawal in the locus ceruleus and ventral tegmental area. J Neurosci 25(25): 6005-6015. 10.1523/jneurosci.0062-05.2005 [PubMed: 15976090] 213. · DOI
  157. Zunhammer M, Schweizer LM, Witte V, Harris RE, Bingel U, et al. 2016. Combined glutamate and glutamine levels in pain-processing brain regions are associated with individual pain sensitivity. Pain 157(10): 2248-2256. 10.1097/j.pain.0000000000000634 [PubMed: 27649042] 214. · DOI
  158. Lötsch J, Skarke C, Liefhold J, Geisslinger G. 2004. Genetic predictors of the clinical response to opioid analgesics: clinical utility and future perspectives. Clin Pharmacokinet 43: 1983-1013. 10.2165/00003088-200443140-00003 215. · DOI
  159. Lötsch J, Zimmermann M, Darimont J, Marx C, Dudziak R, et al. 2002. Does the A118G polymorphism at the μ-opioid receptor gene protect against morphine-6-glucuronide toxicity?. J Am Soc Anesthesiology 97(4): 814-819. 10.1097/00000542-200210000-00011 216. · DOI
  160. Wood PB. 2004. Stress and dopamine: implications for the pathophysiology of chronic widespread pain. Med Hypotheses 62(3): 420-424. 10.1016/j.mehy.2003.10.013 [PubMed: 14975515] 217. · DOI
  161. Xu K, Lichtermann D, Lipsky RH, Franke P, Liu X, et al. 2004. Association of specific haplotypes of D2 dopamine receptorgene with vulnerability to heroin dependence in 2 distinct populations. Arch Gen Psychiatry 61(6): 597-606. 10.1001/archpsyc.61.6.597 [PubMed: 15184239] 220. · DOI
  162. Lawford BR, Young RM, Noble EP, Sargent J, Rowell J, et al. 2000. The D2 dopamine receptor A1 allele and opioid dependence: association with heroin use and response to methadone treatment. Am J Med Genet 96(5): 592-598. 10.1002/1096-8628(20001009)96:5<592::aid- ajmg3>3.0.co;2-y [PubMed: 11054765] 221. · DOI
  163. Li Y, Shao C, Zhang D, Zhao M, Lin L, et al. 2006. The effect of dopamine D2, D5 receptor and transporter (SLC6A3) polymorphisms on the cue-elicited heroin craving in Chinese. Am J Med Genet B Neuropsychiatr Genet 141(3): 269-273. 10.1002/ajmg.b.30264 222. · DOI
  164. Huang W, Payne TJ, Ma JZ, Beuten J, Dupont RT, et al. 2009. Significant association of ANKK1 and detection of a functional polymorphism with nicotine dependence in an African-American sample. Neuropsychopharmacology 34(2): 319-330. 10.1038/npp.2008.37 [PubMed: 18354387] 223. · DOI
  165. Horowitz R, Kotler M, Shufman E, Aharoni S, Kremer I, et al. 2000. Confirmation of an excess of the high enzyme activity COMT val allele in heroin addicts in a family-based haplotype relative risk study. Am J Med Genet 96(5): 599-603. [PubMed: 11054766] 224.
  166. Cao L, Li T, Xu K, Liu X. 2002. Association study of heroin-dependence and-287 A/G polymorphism of catechol-O-methyltransferase gene. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 19(6): 499-501. [PubMed: 12476424] 225.
  167. Comings DE, Blake H, Dietz G, Gade-Andavolu R, Legro RS, et al. 1999. The proenkephalin gene (PENK) and opioid dependence. Neuroreport 10(5): 1133-1135. 10.1097/00001756-199904060-00042 [PubMed: 10321497] 226. · DOI
  168. Nikoshkov A, Drakenberg K, Wang X, Horvath MC, Keller E, et al. 2008. Opioid neuropeptide genotypes in relation to heroin abuse: dopamine tone contributes to reversed mesolimbic proenkephalin expression. Proc Natl Acad Sci 105(2): 786-791. 10.1073/pnas.0710902105 [PubMed: 18184800] 227. Galeeva AR, Gareeva AE, Yur'ev EB, Khusnutdinova EK. 2002. VNTR polymorphisms of the serotonin transporter and dopamine transporter genes in male opiate addicts. Mol Biol 36: 462- 466. 228. Bonnet-Brilhault F, Laurent C, Thibaut F, Campion D, Chavand O, et al. 1997. Serotonin transporter gene polymorphism and schizophrenia: an association study. Biol Psychiatry 42(7): 634-636. 10.1016/s0006-3223(97)00320-x [PubMed: 9376461] 229. · DOI
  169. Comings DE, Muhleman D, Gade R, Johnson P, Verde R, et al. 1997. Cannabinoid receptor gene (CNR1): association with iv drug use. Mol Psychiatry 2(2): 161-168. 10.1038/sj.mp.4000247 [PubMed: 9106242] 230. · DOI
  170. Dackis CA, Gold MS. 1985. New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci Biobehav Rev 9(3): 469-477. 10.1016/0149-7634(85)90022-3 [PubMed: 2999657] 231. · DOI · Paper page
  171. Bogomolova EV, Rauschenbach IY, Adonyeva NV, Alekseev AA, Faddeeva NV, et al. 2010. Dopamine down-regulates activity of alkaline phosphatase in Drosophila: the role of D2- like receptors. J Insect Physiol 56(9): 1155-1159. 10.1016/j.jinsphys.2010.03.014 [PubMed: 20303975] 232. Dackis CA, Gold MS, Davies RK, Sweeney DR. 1986. Bromocriptine treatment for cocaine abuse: the dopamine depletion hypothesis. Int J Psychiatry Med 15(2): 125-135. 10.2190/ gxpa-98ak-4rr4-hd9b 233. · DOI
  172. Blum K, Han D, Baron D, Kazmi S, Elman I, et al. 2022. Nicotinamide adenine dinucleotide (NAD+) and enkephalinase inhibition (IV1114589NAD) infusions significantly attenuate psychiatric burden sequalae in substance use disorder (SUD) in fifty cases. Curr Psychiatry Res Rev 18(2): 125-143. 10.2174/2666082218666220527114427 [PubMed: 36118157] 234. · DOI
  173. Blum K, Baron D, McLaughlin T, Thanos PK, Dennen C, et al. 2024. Summary document research on RDS anti-addiction modeling: annotated bibliography. J Addict Psychiatry 8(1): 1- 33. [PubMed: 38765881] 235.
  174. Blum K, Chen TJ, Bailey J, Bowirrat A, Femino J, et al. 2011. Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?. Mol Neurobiol 44: 250-268. 10.1007/s12035-011-8206-0 [PubMed: 21948099] 236. · DOI
  175. Hill E, Han D, Dumouchel P, Dehak N, Quatieri T, et al. 2013. Long term Suboxone ™ emotional reactivity as measured by automatic detection in speech. PLoS One 8(7): e69043. 10.1371/ journal.pone.0069043 [PubMed: 23874860] 237. · DOI
  176. Blum K, Liu Y, Wang W, Wang Y, Zhang Y, et al. 2015. rsfMRI effects of KB220Z ™ on neural pathways in reward circuitry of abstinent genotyped heroin addicts. Postgrad Med 127(2): 232- 241. 10.1080/00325481.2015.994879 [PubMed: 25526228] 238. · DOI
  177. Bailey GL, Herman DS, Stein MD. 2013. Perceived relapse risk and desire for medication assisted treatment among persons seeking inpatient opiate detoxification. J Subst Abuse Treat 45(3): 302-305. 10.1016/j.jsat.2013.04.002 [PubMed: 23786852] 239. · DOI
  178. Thanos PK, Michaelides M, Umegaki H, Volkow ND. 2008. D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats. Synapse 62(7): 481-486. 10.1002/ syn.20523 [PubMed: 18418874] 240. · DOI · Paper page
  179. Thanos PK, Rivera SN, Weaver K, Grandy DK, Rubinstein M, et al. 2005. Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking. Life Sci 77(2): 130-139. 10.1016/j.lfs.2004.10.061 [PubMed: 15862598] 242. · DOI · Paper page
  180. Scott WC, Kaiser D, Othmer S, Sideroff SI. 2005. Effects of an EEG biofeedback protocol on a mixed substance abusing population. Am J Drug Alcohol Abuse 31(3): 455-469. 10.1081/ ada-200056807 [PubMed: 16161729] 243. · DOI
  181. Peniston EG, Kulkosky PJ. 1990. Alcoholic personality and alpha-theta brainwave training. Med Psychother Int J 3: 37-55. 244. Kirk HW. 2015. Restoring the Brain: Neurofeedback as an Integrative Approach to Health. CRC Press. 245.
  182. Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann KA, et al. 2003. Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 6(1): 43-50. 10.1038/nn980 [PubMed: 12469126] 246. · DOI
  183. Metea MR, Newman EA. 2006. Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling. J Neurosci 26(11): 2862-2870. 10.1523/jneurosci.4048-05.2006 [PubMed: 16540563] 247. · DOI
  184. Colon-Perez LM, Tran K, Thompson K, Pace MC, Blum K, et al. 2016. The psychoactive designer drug and bath salt constituent MDPV causes widespread disruption of brain functional connectivity. Neuropsychopharmacology 41(9): 2352-2365. 10.1038/npp.2016.40 [PubMed: 26997298] 248. · DOI
  185. McLaughlin T, Blum K, Oscar-Berman M, Febo M, Demetrovics Z, Agan G, et al. 2015. Using the neuroadaptagen KB200z ™ to ameliorate terrifying, lucid nightmares in RDS patients: the role of enhanced, brain-reward, functional connectivity and dopaminergic homeostasis. J Reward Defic Syndr 1(1): 24-35. 10.17756/jrds.2015-006 [PubMed: 26065033] 249. · DOI
  186. McLaughlin T, Blum K, Oscar-Berman M, Febo M, Agan G, et al. 2015. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy. J Behav Addict 4(2): 106-115. 10.1556/2006.4.2015.008 [PubMed: 26132915] 250. · DOI
  187. Blum K, Simpatico T, Febo M, Rodriquez C, Dushaj K, et al. 2017. Hypothesizing music intervention enhances brain functional connectivity involving dopaminergic recruitment: common neuro-correlates to abusable drugs. Mol Neurobiol 54(5): 3753-3758. 10.1007/ s12035-016-9934-y [PubMed: 27246565] 251. · DOI
  188. McLaughlin T, Febo M, Badgaiyan RD, Barh D, Dushaj K, et al. 2016. KB220Z ™ a pro- dopamine regulator associated with the protracted, alleviation of terrifying lucid dreams. Can we infer neuroplasticity-induced changes in the reward circuit?. J Reward Defic Syndr Addict Sci 2(1): 3-13. 10.17756/jrdsas.2016-022 [PubMed: 28210713] 252. Chen TJ, Blum K, Chen AL, Bowirrat A, Downs WB, et al. 2011. Neurogenetics and clinical evidence for the putative activation of the brain reward circuitry by a neuroadaptagen: proposing an addiction candidate gene panel map. J Psychoactive Drugs 43(2): 108-127. 10.1080/02791072.2011.587393 [PubMed: 21858957] 253. · DOI
  189. Joutsa J, Moussawi K, Siddiqi SH, Abdolahi A, Drew W, et al. 2022. Brain lesions disrupting addiction map to a common human brain circuit. Nat Med 28(6): 1249-1255. 10.1038/ s41591-022-01834-y [PubMed: 35697842] 254. · DOI
  190. Parker JG, Wanat MJ, Soden ME, Ahmad K, Zweifel LS, et al. 2011. Attenuating GABAA receptor signaling in dopamine neurons selectively enhances reward learning and alters risk preference in mice. J Neurosci 31(47): 17103-17112. 10.1523/jneurosci.1715-11.2011 [PubMed: 22114279] 259. · DOI
  191. Blum K, Giordano J, Morse S, Liu Y, Tan J, et al. 2010. Genetic addiction risk score (GARS) analysis: exploratory development of polymorphic risk alleles in poly-drug addicted males. IIOAB J 1(2): 169-175. 260.
  192. Jenner P, Marsden CD. 1987. Chronic pharmacological manipulation of dopamine receptors in brain. Neuropharmacology 26(7): 931-940. 10.1016/0028-3908(87)90072-4 [PubMed: 2889159] 261. · DOI
  193. Blum K, Oscar-Berman M, Stuller E, Miller D, Giordano J, et al. 2012. Neurogenetics and nutrigenomics of neuro-nutrient therapy for reward deficiency syndrome (RDS): clinical ramifications as a function of molecular neurobiological mechanisms. J Addict Res Ther 3(5): 139. 10.4172/2155-6105.1000139 [PubMed: 23926462] 262. · DOI · Paper page
  194. Luigjes J, Segrave R, de Joode N, Figee M, Denys D. 2019. Efficacy of invasive and non-invasive brain modulation interventions for addiction. Neuropsychology Rev 29: 116-138. 10.1007/ s11065-018-9393-5 263. · DOI
  195. Antonelli M, Fattore L, Sestito L, Di Giuda D, Diana M, et al. 2021. Transcranial magnetic stimulation: a review about its efficacy in the treatment of alcohol, tobacco and cocaine addiction. Addict Behav 114: 106760. 10.1016/j.addbeh.2020.106760 [PubMed: 33316590] 264. · DOI
  196. Schummers J, Yu H, Sur M. 2008. Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320(5883): 1638-1643. 10.1126/ science.1156120 [PubMed: 18566287] 265. · DOI
  197. Sasaki T, Kuga N, Namiki S, Matsuki N, Ikegaya Y. 2011. Locally synchronized astrocytes. Cereb Cortex 21(8): 1889-1900. 10.1093/cercor/bhq256 [PubMed: 21212170] 266. · DOI
  198. Poskanzer KE, Yuste R. 2011. Astrocytic regulation of cortical UP states. Proc Natl Acad Sci 108(45): 18453-18458. 10.1073/pnas.1112378108 [PubMed: 22027012] 267. Sofroniew MV, Vinters HV. 2010. Astrocytes: biology and pathology. Acta Neuropathol 119: 7-35. 10.1007/s00401-009-0619-8 [PubMed: 20012068] 268. · DOI
  199. Blum K, Downs BW, Dushaj K, Li M, Braverman ER, et al. 2016. The benefits of customized DNA directed nutrition to balance the brain reward circuitry and reduce addictive behaviors. Precis Med 1(1): 18-33. 269. Wise EA, Price DD, Myers CD, Heft MW, Robinson ME. 2002. Gender role expectations of pain: relationship to experimental pain perception. Pain 96(3): 335-342. 10.1016/ s0304-3959(01)00473-0 [PubMed: 11973007] 270. · DOI
  200. Moran M, Blum K, Ponce JV, Lott L, Gondré-Lewis MC, et al. 2021. High genetic addiction risk score (GARS) in chronically prescribed severe chronic opioid probands attending multi-pain clinics: an open clinical pilot trial. Mol Neurobiol 58: 3335-3346. 10.1007/s12035-021-02312-1 [PubMed: 33683627] 271. · DOI

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Authors
Zeine, F., Jafari, N., Baron, D. A., Bowirrat, A., Pinhasov, A., Norling, B., Martinez, K. C., Nami, M., Manavi, N., Sunder, K. R., Rabin, D. M., Bagchi, D., Khalsa, J. H., Gold, M. S., Sipple, D., Barzegar, M., Bodhanapati, J., Khader, W., Carney, P. R., Dennen, C. A., Gupta, A., Elman, I., Badgaiyan, R. D., Modestino, E. J., Thanos, P. K., Hanna, C., McLaughlin, T., Cadet, J. L., Soni, D., Braverman, E. R., Barh, D., Giordano, J., Edwards, D., Ashford, J. W., Gondré‐Lewis, M. C., Gilley, E., Murphy, K. T., Lewandrowski, K.-U., Sharafshah, A., Makale, M., Fuehrlein, B., & Blum, K.
Affiliations
  • California State University, Long Beach (US)
  • The Chicago School (US)
  • Western University of Health Sciences (US)
  • Ariel University (IL)
  • Berkeley College (US)
  • University of California, Riverside (US)
  • Texas Southern University (US)
  • University of Maryland, Baltimore (US)
  • Washington University in St. Louis (US)
  • National Center for Cancer Care and Research (QA)
  • Werfen (United States) (US)
  • University of Missouri (US)
  • Thomas Jefferson University Hospital (US)
  • Harvard University (US)
  • MetroHealth (US)
  • Curry College (US)
  • University at Buffalo, State University of New York (US)
  • National Institutes of Health (US)
  • St. Clare Hospital in Lakewood (US)
  • Stanford University (US)
  • Howard University (US)
  • University of California San Diego (US)
  • Hospital Universitário Gaffrée e Guinle (BR)
  • Guilan University of Medical Sciences (IR)
  • Yale University (US)
  • Eötvös Loránd University (HU)
ORCID
Venue
Journal of Addiction Psychiatry
Publisher
United Scientific Group
Published
2024-06-20
Volume
8
Issue
1
Pages
50-95
ISSN
3065-5889 (ISSN-L)
DOI
10.17756/jap.2024-045
PMC
PMC11615735
OpenAlex
W4405091801
Cited by
3
References
25
Citations by year
2026: 1 · 2025: 2
FWCI
1.09
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Journal of Addiction Psychiatry (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
Funders
  • U.S. Department of Veterans Affairs (I01 CX002099, I01 CX000479)
  • Guilan University of Medical Sciences
  • National Institutes of Health (DA045640)
  • National Institute on Drug Abuse (R33DA045640, R21DA045640)
  • National Institute on Minority Health and Health Disparities (R41MD012318)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords
opioid epidemic, opioid use disorder, dopamine homeostasis, opioid substitution therapy, harm reduction, opioid overdose deaths, epigenetics, reward systems, addiction prevention

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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