EC Neurology

Review Article Volume 17 Issue 5 - 2025

Neurogenetics and Epigenetics of Spirituality and Religion: Seeking Genospirituality Via the Lens of Hierarchical Neuro-Spiritual Model (HNSM)

Kai-Uwe Lewandrowski1-4,25*, Kenneth Blum5-8,25**, Morgan P Lorio9, Alireza Sharafshah10, Abdalla Bowirrat5, Albert Pinhasov5, Panayotis K Thanos5,11, Catherine A Dennen12, Igor Elman5,13, David Baron14-16, Alexander PL Lewandrowski17, Alexander R Vaccaro18, Óscar L Alves19, Milan T Makale20, Rajendra D Badgaiyan21, Gianni Martire7, Thomas Simpatico8, Abdalla Bowirrat5, Albert Pinhasov5, William J Heaney7,22, Debasis Bagchi23, Rossano Kepler Alvim Fiorelli24 and Sergio Luis Schmidt25,26

1Division of Personalized Pain Therapy Research and Education, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ, USA 2Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá, DC, Colombia 3Department of Surgery, Arizona University School of Medicine, Tucson, AZ, USA 4Department of Orthopaedics, Universidade Federal do Estado do Rio de Janeiro, Brazil 5Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel 6Division of Addiction Research and Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA, USA 7Division of Clinical Neurology, The Blum Institute of Neurogenetics and Behavior, Austin, TX, USA 8Department of Psychiatry, University of Vermont, School of Medicine, Burlington, VT, USA 9Advanced Orthopedics, Altamonte Springs, On Behalf of the International Society for the Advancement of Spine Surgery, 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 Psychology, University of Buffalo, Buffalo, NY, USA 12Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA 13Department of Psychiatry and Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA 14Division of Addiction Research and Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA, USA 15Department of Psychiatry and Behavioral Sciences, Stanford University, School of Medicine, Palo Alto, CA, USA 16Division of Addiction Research and Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA, USA 17Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA 18Chairman of the Department of Ort hopaedic Surgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA 19Head of Neurosurgery, Hospital Lusíadas Porto, Senior Consultant in Neurosurgery, ULS Gaia Espinho, Portugal 20Department of Radiation Medicine and Applied Sciences, UC San Diego, La Jolla, CA, USA 21Department of Psychiatry, Texas Tech University Health Science Center, Midland, TX, USA 22Division of Pain Modulation, Electronic Waveform Laboratory, Huntington Beach, CA, USA 23Department of Pharmaceutical Sciences, Texas Southern University College of Pharmacy, Houston, TX, USA 24Department of General and Specialized Surgery, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro-RJ, Brazil 25Department of Neurology, Federal University of the State of Rio de Janeiro (UNIRIO), RJ, Brazil 26University Hospital - Rua Mariz e Barros 750 - Tijuca, Rio de Janeiro, RJ, Brazil

*Corresponding Author: Kai-Uwe Lewandrowski, Division of Personalized Pain Therapy Research and Education, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ, USA.
Received: March 31, 2025; Published: April 04, 2025



Addictive behaviors-including the misuse of tobacco, alcohol, illicit substances, and compulsive activities such as gambling, overeating, and sexual excess-remain widespread and profoundly burdensome on both individuals and societies. Their impact is multifaceted, encompassing adverse health outcomes, increased criminal activity, and significant economic costs due to lost productivity. Addiction is a highly complex condition shaped by genetic predispositions, environmental influences, and behavioral factors, all of which contribute to disruptions in neural regulation and compulsive decision-making. While advances have been made in identifying the genetic and biochemical underpinnings of addiction and related psychiatric disorders, progress in developing broadly effective therapies has been limited.

Addiction is often characterized by feelings of fragmentation, helplessness, and existential despair-phenomena that may reflect a deeper, unmet need for personal integration, purpose, and transformation. This perspective supports the notion that spiritual yearning can be an integral part of the recovery process. Efforts to address addiction have frequently overlooked the potential therapeutic value of spirituality in fostering healing. If one accepts the premise that the brain governs both conscious and unconscious experience-including religious and spiritual phenomena-it follows that addiction, and mental illness may involve disrupted neural systems that regulate reward and suffering. We propose that individuals may have differing capacities for spiritual resilience or growth based on a dynamic interplay between their genetic architecture and epigenetic factors (e.g. life experiences, trauma, social environment). This expert opinion presents current evidence supporting this hypothesis and highlights the relevance of the Hierarchical Neuro-Spiritual Model (HNSM) as a novel framework for understanding the spiritual dimension in the pathophysiology and treatment of addiction.

 Keywords: Reward Deficiency Syndrome (RDS); Genes; Dopaminergic; Reward Dependence; Spirituality; Addiction Recovery; Twelve Steps; Hierarchical Neuro-Spiritual Model (HNSM)

  1. Perry BD and Szalavitz M. “The boy who was raised as a dog: And other stories from a child psychiatrist's notebook--What traumatized children can teach us about loss, love, and healing”. Hachette UK (2017).
  2. Blum K., et al. “Springer Briefs in Neuroscience”. New York: Springer (2013).
  3. Hodge CW and Cox AA. “The discriminative stimulus effects of ethanol are mediated by NMDA and GABAA receptors in specific limbic brain regions”. Psychopharmacology1-2 (1998): 95-107.
  4. Hodge CW., et al. “Dopamine receptors in the medial prefrontal cortex influence ethanol and sucrose‐reinforced responding”. Alcoholism: Clinical and Experimental Research9 (1996): 1631-1638.
  5. Blum K., et al. “Alcohol and behaviour: basic and clinical aspects”. Progress in Alcohol Research (1990).
  6. Comings DE and Blum K. “Reward deficiency syndrome: genetic aspects of behavioral disorders”. Progress in Brain Research 126 (2000): 325-341.
  7. Bau CH., et al. “The TaqI A1 allele of the dopamine D2 receptor gene and alcoholism in Brazil: association and interaction with stress and harm avoidance on severity prediction”. American Journal of Medical Genetics 3 (2000): 302-306.
  8. Blum K., et al. “Increased prevalence of the Taq I A1allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorder: a preliminary report”. Pharmacogenetics and Genomics4 (1996): 297-305.
  9. Blum K., et al. “The D2 dopamine receptor gene as a determinant of reward deficiency syndrome”. Journal of the Royal Society of Medicine7 (1996): 396-400.
  10. Blum K., et al. “Generational association studies of dopaminergic genes in reward deficiency syndrome (RDS) subjects: selecting appropriate phenotypes for reward dependence behaviors”. International Journal of Environmental Research and Public Health 12 (2011): 4425-4459.
  11. Thomas M., et al. “Neuroplasticity in the mesolimbic dopamine system and cocaine addiction”. British Journal of Pharmacology2 (2008): 327-342.
  12. Brunner HG., et al. “Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A”. Science 5133 (1993): 578-580.
  13. Gold M and Dackis C. “New insights and treatments: opiate withdrawal and cocaine addiction”. Clinical Therapeutics1 (1984): 6-21.
  14. Gold MS. “Opiate addiction and the locus coeruleus: the clinical utility of clonidine, naltrexone, methadone, and buprenorphine”. Psychiatric Clinics 1 (1993): 61-73.
  15. Dackis C and Gold M. “Neurotransmitter and neuroendocrine abnormalities associated with cocaine use”. Psychiatric Medicine 3 (1985): 461-483.
  16. Miller NS and Gold MS. “Dissociation of “conscious desire” (craving) from and relapse in alcohol and cocaine dependence”. Annals of Clinical Psychiatry2 (1994): 99-106.
  17. Grandy DK., et al. “The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a TaqI RFLP”. American Journal of Human Genetics5 (1989): 778-785.
  18. Hauge XY., et al. “Detection and characterization of additional DNA polymorphisms in the dopamine D2 receptor gene”. Genomics 3 (1991): 527-530.
  19. Blum K., et al. “Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour”. Pharmacogenetics and Genomics3 (1995): 121-141.
  20. Blum K., et al. “The reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive and compulsive behaviors”. Journal of Psychoactive Drugs 32 (2000): 1-112.
  21. Blum K., et al. “Sex, drugs, and rock ‘n’roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms”. Journal of Psychoactive Drugs1 (2012): 38-55.
  22. Di Chiara G and Imperato A. “Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats”. Proceedings of the National Academy of Sciences14 (1988): 5274-5278.
  23. Tomasi D and Volkow ND. “Brain activation and neurochemistry”. Proceedings of the National Academy of Sciences 27 (2013): 10888-10889.
  24. Eisenberg DT., et al. “Season of birth and dopamine receptor gene associations with impulsivity, sensation seeking and reproductive behaviors”. PLoS One11 (2007): e1216.
  25. Blum K., et al. “Neurogenetics and nutrigenomics of neuro-nutrient therapy for reward deficiency syndrome (RDS): clinical ramifications as a function of molecular neurobiological mechanisms”. Journal of Addiction Research and Therapy5 (2012): 139.
  26. Hietala J., et al. “Striatal D2 dopamine receptor characteristics in neuroleptic-naive schizophrenic patients studied with positron emission tomography”. Archives of General Psychiatry2 (1994): 116-123.
  27. Hietala J., et al. “Striatal D 2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence”. Psychopharmacology3 (1994): 285-290.
  28. Hill E., et al. “Long term Suboxone™ emotional reactivity as measured by automatic detection in speech”. PLoS one 7 (2013): e69043.
  29. Rothman RB., et al. “Dual dopamine/serotonin releasers as potential medications for stimulante and alcohol addictions”. The AAPS Journal1 (2007): E1-E10.
  30. Boundy VA., et al. “Agonists and antagonists differentially regulate the high affinity state of the D2L receptor in human embryonic kidney 293 cells”. Molecular Pharmacology5 (1995): 956-964.
  31. Thanos PK., et al. “D2R DNA transfer into the nucleus accumbens attenuates cocaine self‐administration in rats”. Synapse 7 (2008): 481-486.
  32. Thanos PK., et al. “Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking”. Life Sciences2 (2005): 130-139.
  33. Thanos PK., et al. “Overexpression of dopamine D2 receptors reduces alcohol self‐administration”. Journal of Neurochemistry5 (2001): 1094-1103.
  34. Myers R and Robinson D. “Mμ and D2 receptor antisense oligonucleotides injected in nucleus accumbens suppress high alcohol intake in genetic drinking HEP rats”. Alcohol 2-3 (1999): 225-233.
  35. Dahlgren A., et al. “Do alcohol-dependent individuals with DRD2 A1 allele have an increased risk of relapse? A pilot study”. Alcohol and Alcoholism5 (2011): 509-513.
  36. Beley TG. “Beyond Addictioned”. Author House (2014).
  37. Blum K., et al. “Dopamine genetics and function in food and substance abuse”. Journal of Genetic Syndrome and Gene Therapy121 (2013): 1000121.
  38. Robbins TW and Everitt BJ. “Neurobehavioural mechanisms of reward and motivation”. Current Opinion in Neurobiology 2 (1996): 228-236.
  39. Wightman RM and Robinson DL. “Transient changes in mesolimbic dopamine and their association with ‘reward’”. Journal of Neurochemistry4 (2002): 721-735.
  40. Caine SB., et al. “Effects of the dopamine D-1 antagonist SCH 23390 microinjected into the accumbens, amygdala or striatum on cocaine self-administration in the rat”. Brain Research1-2 (1995): 47-56.
  41. Epping-Jordan MP., et al. “The dopamine D-1 receptor antagonist SCH 23390 injected into the dorsolateral bed nucleus of the stria terminalis decreased cocaine reinforcement in the rat”. Brain Research1-2 (1998): 105-115.
  42. Suhara T., et al. “Dopamine D2 receptors in the insular cortex and the personality trait of novelty seeking”. Neuroimage 5 (2001): 891-895.
  43. James GA., et al. “Interaction of satiety and reward response to food stimulation”. Journal of Addictive Diseases3 (2004): 23-37.
  44. Fort J. “The pleasure seekers: The drug crisis, youth and society”. (No Title) (1969).
  45. Norbury A., et al. “Dopamine modulates risk-taking as a function of baseline sensation-seeking trait”. Journal of Neuroscience32 (2013): 12982-12986.
  46. Miller NS and Gold MS. “Criminal activity and crack addiction”. International Journal of the Addictions8 (1994): 1069-1078.
  47. Bruijnzeel AW and Gold MS. “The role of corticotropin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence”. Brain Research Reviews3 (2005): 505-528.
  48. Gold MS and Herkov MJ. “Tobacco smoking and nicotine dependence: biological basis for pharmacotherapy from nicotine to treatments that prevent relapse”. Journal of Addictive Diseases1 (1998): 7-21.
  49. Blumenthal DM and Gold MS. “Neurobiology of food addiction”. Current Opinion in Clinical Nutrition and Metabolic Care4 (2010): 359-365.
  50. Blum K., et al. “Do dopaminergic gene polymorphisms affect mesolimbic reward activation of music listening response? Therapeutic impact on Reward Deficiency Syndrome (RDS)”. Medical Hypotheses3 (2010): 513-520.
  51. Volkow ND., et al. “Unbalanced neuronal circuits in addiction”. Current Opinion in Neurobiology4 (2013): 639-48.
  52. Blum K., et al. ““Liking” and “wanting” linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry”. Current Pharmaceutical Design1 (2012): 113-118.
  53. McNamara P. “The neuroscience of religious experienced”. Cambridge University Press (2009).
  54. Wildman WJ. “Religious and spiritual experienced”. Cambridge University Press (2011).
  55. Nilsson KW., et al. “Genes encoding for AP-2β and the serotonin transporter are associated with the personality character spiritual acceptance”. Neuroscience Letters3 (2007): 233-237.
  56. Comings DE., et al. “The DRD4 gene and the spiritual transcendence scale of the character temperament index”. Psychiatric Genetics 4 (2000): 185-189.
  57. Hamer DH. “The God gene: How faith is hardwired into our genesed”. Anchor (2005).
  58. Comings DE. “Did Man Create God?: is Your Spiritual Brain at Peace with Your Thinking Brain?: Including Intelligent Answers to Intelligent Designed”. Hope Press (2008).
  59. Newberg A. “The brain and the biology of belief: An interview with Andrew Newberg, MD. Interview by Nancy Nachman-Hunt”. Advances in Mind-Body Medicine1 (2009): 32-36.
  60. Archer T., et al. “Neurogenetics and epigenetics in impulsive behaviour: impact on reward circuitry”. Journal of Genetic Syndrome and Gene Therapy3 (2012): 1000115.
  61. Cloninger CR., et al. “A psychobiological model of temperament and character”. Archives of General Psychiatry12 (1993): 975-990.
  62. Asghari V., et al. “Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants”. Journal of Neurochemistry3 (1995): 1157-1165.
  63. Cohen HL., et al. “Religion and spirituality as defined by older adults”. Journal of Gerontological Social Work3-4 (2008): 284-299.
  64. Cohen MX., et al. “Connectivity-based segregation of the human striatum predicts personality characteristics”. Nature Neuroscience1 (2009): 32-34.
  65. Comings D., et al. “A multivariate analysis of 59 candidate genes in personality traits: the temperament and character inventory”. Clinical Genetics5 (2000): 375-385.
  66. Borg J., et al. “The serotonin system and spiritual experiences”. American Journal of Psychiatry11 (2003): 1965-1969.
  67. Bachner-Melman R., et al. “AVPR1a and SLC6A4 gene polymorphisms are associated with creative dance performance”. PLoS Genetics3 (2005): e42.
  68. Rossi E. “The bioinformatics of psychosocial genomics in alternative and complementary medicine”. Forschende Komplementärmedizin und Klassische Naturheilkunde/Research in Complementary and Classical Natural Medicine 3 (2003): 143-150.
  69. Kendler KS and Myers J. “A developmental twin study of church attendance and alcohol and nicotine consumption: A model for analyzing the changing impact of genes and environment”. American Journal of Psychiatry 10 (2009): 1150-1155.
  70. Boomsma DI., et al. “A religious upbringing reduces the influence of genetic factors on disinhibition: evidence for interaction between genotype and environment on personality”. Twin Research 2 (1999): 115-125.
  71. Koopmans JR., et al. “The influence of religion on alcohol use initiation: evidence for genotype X environment interaction”. Behavior Genetics6 (1999): 445-453.
  72. Haber JR., et al. “Religion/spirituality, risk, and the development of alcohol dependence in female twins”. Psychology of Addictive Behaviors3 (2013): 562-572.
  73. Levin M. “Screening Jews and genes: a consideration of the ethics of genetic screening within the Jewish community: challenges and responses”. Genetic Testing 2 (1999): 207-213.
  74. Rosmarin DH., et al. “A test of faith in God and treatment: the relationship of belief in God to psychiatric treatment outcomes”. Journal of Affective Disorders 3 (2013): 441-446.
  75. Schoenthaler SJ., et al. “NIDA-drug addiction treatment outcome study (DATOS) relapse as a function of spirituality/religiosity”. Reward Deficiency Syndrome 1 (2015): 36-45.
  76. Zhen-Duan J., et al. “Religion, spirituality, and DNA methylation in HPA-axis genes among Hispanic/Latino adults”. Epigenomics3 (2025): 155-166.
  77. Zahir FR. “Epigenomic impacts of meditative practices”. Epigenomics24 (2022): 1593-1608.
  78. Kjaer TW., et al. “Increased dopamine tone during meditation-induced change of consciousness”. Cognitive Brain Research2 (2002): 255-259.
  79. Koepp MJ., et al. “Evidence for striatal dopamine release during a video game”. Nature 6682 (1998): 266-268.
  80. Holmes Jr L., et al. “Implication of spiritual network support system in epigenomic modulation and health trajectory”. International Journal of Environmental Research and Public Health21 (2019): 4123.
  81. Martire G., et al. “Theorizing that psychedelic assisted therapy may play a role in the treatment of trauma-induced personality disorders”. Journal of Addiction Psychiatry2 (2024): 161-165.
  82. Fan L., et al. “Structural basis of psychedelic LSD recognition at dopamine D1 receptor”. Neuron19 (2024): 3295-3310.e8.
  83. Cao C., et al. “Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD”. Neuron 19 (2022): 3154-3167.e7.
  84. Passie T., et al. “The pharmacology of lysergic acid diethylamide: a review”. CNS Neuroscience and Therapeutics4 (2008): 295-314.
  85. Modell SM., et al. “When genetics meets religion: what scientists and religious leaders can learn from each other”. Public Health Genomics5-6 (2020): 174-188.
  86. Estévez M. “Chapter 3. The seven capital sins: genesis, virtues, demons and rights”. Journal International de Bioethique et D'ethique des Sciences1 (2020): 31-42.
  87. Ghareeb BA. “Human genetics and Islam: scientific and medical aspects”. The Journal of IMA2 (2011): 83-90.
  88. Charlson F., et al. “New WHO prevalence estimates of mental disorders in conflict settings: a systematic review and meta-analysis”. The Lancet10194 (2019): 240-248.
  89. Blum K. “Neurospirituality connectome-role in neurology and reward deficiency syndrome (RDS)”. EC Neurology2 (2025): 01-25.
  90. Casey B., et al. “DSM-5 and RDoC: progress in psychiatry research?” Nature Reviews Neuroscience11 (2013): 810-814.
  91. Kenneth Blum., et al. “Time to admit genes and epigenetics are indeed the blueprint for a rewardful life whereby the organism controls the genome”. Acta Scientific Neurology 1 (2025): 03-09.
  92. Blum K., et al. “Futuristic thinking about engineering “geneospirituality” to help prevent relapse of reward deficiency syndrome (RDS) behaviors”. EC Psychology and Psychiatry3 (2023): 26-32.

Kai-Uwe Lewandrowski., et al. “Neurogenetics and Epigenetics of Spirituality and Religion: Seeking Genospirituality Via the Lens of Hierarchical Neuro-Spiritual Model (HNSM)”. EC Neurology  17.5 (2025): 01-24.

ECronicon Journal

Our Services

Quick Links

Information

Creative Commons LicenseOpen Access by ECronicon is licensed under a Creative Commons Attribution 4.0 International License
Based on a work at www.ecronicon.net