Generic placeholder image

Current Psychopharmacology

Editor-in-Chief

ISSN (Print): 2211-5560
ISSN (Online): 2211-5579

Perspective

Endorphinergic Enhancement Attenuation of Post-traumatic Stress Disorder (PTSD) via Activation of Neuro-immunological Function in the Face of a Viral Pandemic

Author(s): Kenneth Blum*, Edward J. Modestino, David Baron, Raymond Brewer, Panayotis Thanos, Igor Elman, Rajendra D. Badgaiyan, B. William Downs, Debasis Bagchi, Thomas McLaughlin, Abdalla Bowirrat, A. Kenison Roy and Mark S. Gold

Volume 10, Issue 2, 2021

Published on: 04 January, 2021

Article ID: e200323189912 Pages: 12

DOI: 10.2174/2211556009999210104221215

Abstract

Introduction: Polymorphic gene variants, particularly the genetic determinants of low dopamine function (hypodopaminergia), are known to associate with Substance Use Disorder (SUD) and a predisposition to PTSD. Addiction research and molecular genetic applied technologies supported by the National Institutes of Health (NIH) have revealed the complex functions of brain reward circuitry and its crucial role in addiction and PTSD symptomatology.

Discussion: It is noteworthy that Israeli researchers compared mice with a normal immune system with mice lacking adaptive immunity and found that the incidence of PTSD increased several-fold. It is well established that raising endorphinergic function increases immune response significantly. Along these lines, Blum’s work has shown that D-Phenylalanine (DPA), an enkephalinase inhibitor, increases brain endorphins in animal models and reduces stress in humans. Enkephalinase inhibition with DPA treats Post Traumatic Stress Disorder (PTSD) by restoring endorphin function. The Genetic Addiction Risk Severity (GARS) can characterize relevant phenotypes, genetic risk for stress vulnerability vs. resilience. GARS could be used to pre-test military enlistees for adaptive immunity or as part of PTSD management with customized neuronutrient supplementation upon return from deployment.

Conclusion: Based on GARS values, with particular emphasis on enhancing immunological function, pro-dopamine regulation may restore dopamine homeostasis. Recognition of the immune system as a “sixth sense” and assisting adaptive immunity with Precision Behavioral Management (PBM), accompanied by other supportive interventions and therapies, may shift the paradigm in treating stress disorders.

Keywords: Post-traumatic Stress Disorder (PTSD), Genetic Addiction Risk Severity (GARS™), Pro-dopamine regulation(KB220PAM), hypodopaminergia, immune system, endorphinergic.

Graphical Abstract
[1]
Blum K. Reward deficiency syndromeThe SAGE encyclopedia of abnormal and clinical psychology University of Pennsylvania School of Medicine. USA: Sage Publications Inc. 2017.
[2]
Bowirrat A, Chen TJ, Blum K, et al. Neuro-psychopharmacogenetics and neurological antecedents of posttraumatic stress disorder: unlocking the mysteries of resilience and vulnerability. Curr Neuropharmacol 2010; 8(4): 335-58.
[http://dx.doi.org/10.2174/157015910793358123] [PMID: 21629442]
[3]
Elman I, Borsook D. Common brain mechanisms of chronic pain and addiction. Neuron 2016; 89(1): 11-36.
[http://dx.doi.org/10.1016/j.neuron.2015.11.027] [PMID: 26748087]
[4]
Jellinek E. The disease concept of alcoholismItaly: New Heaven: College and University Press. 1960.
[http://dx.doi.org/10.1037/14090-000]
[5]
Davis VE, Walsh MJ. Alcohol addiction and tetrahydropapaveroline. Science 1970; 169(3950): 1105-6.
[PMID: 5465179]
[6]
Hamilton MG, Blum K, Hirst M. Identification of an isoquinoline alkaloid after chronic exposure to ethanol. Alcohol Clin Exp Res 1978; 2(2): 133-7.
[http://dx.doi.org/10.1111/j.1530-0277.1978.tb04713.x] [PMID: 350076]
[7]
Collins MA, Kahn AJ. Attraction to ethanol solutions in mice: induction by a tetrahydroisoquinoline derivative of L-DOPA. Subst Alcohol Actions Misuse 1982; 3(5): 299-302.
[PMID: 7167865]
[8]
Cohen G, Collins M. Alkaloids from catecholamines in adrenal tissue: possible role in alcoholism. Science 1970; 167(3926): 1749-51.
[http://dx.doi.org/10.1126/science.167.3926.1749] [PMID: 5461272]
[9]
Blum K, Hamilton MG, Hirst M, Wallace JE. Putative role of isoquinoline alkaloids in alcoholism: a link to opiates. Alcohol Clin Exp Res 1978; 2(2): 113-20.
[http://dx.doi.org/10.1111/j.1530-0277.1978.tb04710.x] [PMID: 350073]
[10]
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.
[http://dx.doi.org/10.1177/014107689608900711] [PMID: 8774539]
[11]
Brady KT, Killeen TK, Brewerton T, Lucerini S. Comorbidity of psychiatric disorders and posttraumatic stress disorder. J Clin Psychiatry 2000; 61(Suppl. 7): 22-32.
[PMID: 10795606]
[12]
Saunders EC, Lambert-Harris C, McGovern MP, Meier A, Xie H. The prevalence of posttraumatic stress disorder symptoms among addiction treatment patients with cocaine use disorders. J Psychoactive Drugs 2015; 47(1): 42-50.
[http://dx.doi.org/10.1080/02791072.2014.977501] [PMID: 25715071]
[13]
Dackis CA, Gold MS. Bromocriptine as treatment of cocaine abuse. Lancet 1985; 1(8438): 1151-2.
[http://dx.doi.org/10.1016/S0140-6736(85)92448-1] [PMID: 2860349]
[14]
Noble EP, Blum K, Khalsa ME, et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend 1993; 33(3): 271-85.
[http://dx.doi.org/10.1016/0376-8716(93)90113-5] [PMID: 8261891]
[15]
Dackis CA, Gold MS, Sweeney DR, Byron JP Jr, Climko R. Single-dose bromocriptine reverses cocaine craving. Psychiatry Res 1987; 20(4): 261-4.
[http://dx.doi.org/10.1016/0165-1781(87)90086-2] [PMID: 3602212]
[16]
Lawford BR, Young RM, Rowell JA, et al. Bromocriptine in the treatment of alcoholics with the D2 dopamine receptor A1 allele. Nat Med 1995; 1(4): 337-41.
[http://dx.doi.org/10.1038/nm0495-337] [PMID: 7585063]
[17]
Blum K, Noble EP, Sheridan PJ, et al. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 1990; 263(15): 2055-60.
[http://dx.doi.org/10.1001/jama.1990.03440150063027] [PMID: 1969501]
[18]
Bogomolova EV, Rauschenbach IY, Adonyeva NV, Alekseev AA, Faddeeva NV, Gruntenko NE. Dopamine down-regulates activity of alkaline phosphatase in Drosophila: the role of D2-like receptors. J Insect Physiol 2010; 56(9): 1155-9.
[http://dx.doi.org/10.1016/j.jinsphys.2010.03.014] [PMID: 20303975]
[19]
Rouillard C, Bédard PJ, Falardeau P, Dipaolo T. Behavioral and biochemical evidence for a different effect of repeated administration of L-dopa and bromocriptine on denervated versus non-denervated striatal dopamine receptors. Neuropharmacology 1987; 26(11): 1601-6.
[http://dx.doi.org/10.1016/0028-3908(87)90008-6] [PMID: 3431663]
[20]
Blum K, Chen AL, Chen TJ, et al. Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary. Theor Biol Med Model 2008; 5: 24.
[http://dx.doi.org/10.1186/1742-4682-5-24] [PMID: 19014506]
[21]
Blum K, Oscar-Berman M, Stuller E, et al. 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 2012; 3(5): 139.
[PMID: 23926462]
[22]
Thanos PK, Rivera SN, Weaver K, et al. Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking. Life Sci 2005; 77(2): 130-9.
[http://dx.doi.org/10.1016/j.lfs.2004.10.061] [PMID: 15862598]
[23]
Thanos PK, Michaelides M, Umegaki H, Volkow ND. D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats. Synapse 2008; 62(7): 481-6.
[http://dx.doi.org/10.1002/syn.20523] [PMID: 18418874]
[24]
Blum K, Febo M, Badgaiyan RD. Fifty years in the development of a glutaminergic-dopaminergic optimization complex (KB220) to balance brain reward circuitry in reward deficiency syndrome: a pictorial. Austin Addict Sci 2016; 1(2): 1006.
[25]
Febo M, Blum K, Badgaiyan RD, et al. Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z. PLoS One 2017; Apr 26;. 12(4)e0174774
[http://dx.doi.org/10.1371/journal.pone.0174774] [PMID: 28445527]
[26]
Blum K, Liu Y, Wang W, et al. rsfMRI effects of KB220Z™ on neural pathways in reward circuitry of abstinent genotyped heroin addicts. Postgrad Med 2015; 127(2): 232-41.
[http://dx.doi.org/10.1080/00325481.2015.994879] [PMID: 25526228]
[27]
Philip NS, Carpenter SL, Sweet LH. Developing neuroimaging phenotypes of the default mode network in PTSD: integrating the resting state, working memory, and structural connectivity. J Vis Exp 2014; Jul 1;. (89): 51651.
[http://dx.doi.org/10.3791/51651]
[28]
O’Doherty DCM, Tickell A, Ryder W, et al. Frontal and subcortical grey matter reductions in PTSD. Psychiatry Res Neuroimaging 2017; 266: 1-9.
[http://dx.doi.org/10.1016/j.pscychresns.2017.05.008] [PMID: 28549317]
[29]
O’Doherty DC, Chitty KM, Saddiqui S, Bennett MR, Lagopoulos J. A systematic review and meta-analysis of magnetic resonance imaging measurement of structural volumes in posttraumatic stress disorder. Psychiatry Res 2015; 232(1): 1-33.
[http://dx.doi.org/10.1016/j.pscychresns.2015.01.002] [PMID: 25735885]
[30]
Logue MW, van Rooij SJH, Dennis EL, et al. Smaller hippocampal volume in posttraumatic stress disorder: a multisite ENIGMA-PGC study: subcortical volumetry results from posttraumatic stress disorder consortia. Biol Psychiatry 2018; 83(3): 244-53.
[http://dx.doi.org/10.1016/j.biopsych.2017.09.006] [PMID: 29217296]
[31]
Akiki TJ, Averill CL, Wrocklage KM, et al. The Association of PTSD Symptom Severity with Localized Hippocampus and Amygdala Abnormalities. Chronic Stress (Thousand Oaks) 2017; 1: 1.
[http://dx.doi.org/10.1177/2470547017724069] [PMID: 28825050]
[32]
Martindale SL, Rowland JA, Shura RD, Taber KH. Longitudinal changes in neuroimaging and neuropsychiatric status of post-deployment veterans: a CENC pilot study. Brain Inj 2018; 32(10): 1208-16.
[http://dx.doi.org/10.1080/02699052.2018.1492741] [PMID: 29985673]
[33]
Averill LA, Abdallah CG, Pietrzak RH, et al. Combat exposure severity is associated with reduced cortical thickness in combat veterans: a preliminary report. Chronic Stress (Thousand Oaks) 2017; 1: 1.
[http://dx.doi.org/10.1177/2470547017724714] [PMID: 28845475]
[34]
van Wingen GA, Geuze E, Caan MW, et al. Persistent and reversible consequences of combat stress on the mesofrontal circuit and cognition. Proc Natl Acad Sci USA 2012; 109(38): 15508-13.
[http://dx.doi.org/10.1073/pnas.1206330109] [PMID: 22949649]
[35]
Butler O, Willmund G, Gleich T, Gallinat J, Kühn S, Zimmermann P. Hippocampal gray matter increases following multimodal psychological treatment for combat-related post-traumatic stress disorder. Brain Behav 2018; 8(5)e00956
[http://dx.doi.org/10.1002/brb3.956] [PMID: 29761009]
[36]
Blum K, Gardner E, Oscar-Berman M, Gold M. “Liking” and “wanting” linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry. Curr Pharm Des 2012; 18(1): 113-8.
[http://dx.doi.org/10.2174/138161212798919110] [PMID: 22236117]
[37]
Blum K, Giordano J, Oscar-Berman M, Bowirrat A, Simpatico T, Barh D. Diagnosis and healing in veterans suspected of suffering from post-traumatic stress disorder (ptsd) using reward gene testing and reward circuitry natural dopaminergic activation. J Genet Syndr Gene Ther 2012; 3(3)1000116
[http://dx.doi.org/10.4172/2157-7412.1000116] [PMID: 23264885]
[38]
Filiano AJ, Gadani SP, Kipnis J. How and why do T cells and their derived cytokines affect the injured and healthy brain? Nat Rev Neurosci 2017; 18(6): 375-84.
[http://dx.doi.org/10.1038/nrn.2017.39] [PMID: 28446786]
[39]
Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR, Schwartz M. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 1999; 5(1): 49-55.
[http://dx.doi.org/10.1038/4734] [PMID: 9883839]
[40]
Kipnis J, Yoles E, Porat Z, et al. T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: possible therapy for optic neuropathies. Proc Natl Acad Sci USA 2000; 97(13): 7446-51.
[http://dx.doi.org/10.1073/pnas.97.13.7446] [PMID: 10861010]
[41]
Kipnis J, Yoles E, Schori H, Hauben E, Shaked I, Schwartz M. Neuronal survival after CNS insult is determined by a genetically encoded autoimmune response. J Neurosci 2001; 21(13): 4564-71.
[http://dx.doi.org/10.1523/JNEUROSCI.21-13-04564.2001] [PMID: 11425884]
[42]
Hauben E, Butovsky O, Nevo U, et al. Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J Neurosci 2000; 20(17): 6421-30.
[http://dx.doi.org/10.1523/JNEUROSCI.20-17-06421.2000] [PMID: 10964948]
[43]
Yoles E, Hauben E, Palgi O, et al. Protective autoimmunity is a physiological response to CNS trauma. J Neurosci 2001; 21(11): 3740-8.
[http://dx.doi.org/10.1523/JNEUROSCI.21-11-03740.2001] [PMID: 11356861]
[44]
Kipnis J, Cohen H, Cardon M, Ziv Y, Schwartz M. T cell deficiency leads to cognitive dysfunction: implications for therapeutic vaccination for schizophrenia and other psychiatric conditions. Proc Natl Acad Sci USA 2004; 101(21): 8180-5.
[http://dx.doi.org/10.1073/pnas.0402268101] [PMID: 15141078]
[45]
Brynskikh A, Warren T, Zhu J, Kipnis J. Adaptive immunity affects learning behavior in mice. Brain Behav Immun 2008; 22(6): 861-9.
[http://dx.doi.org/10.1016/j.bbi.2007.12.008] [PMID: 18249087]
[46]
Radjavi A, Smirnov I, Kipnis J. Brain antigen-reactive CD4+ T cells are sufficient to support learning behavior in mice with limited T cell repertoire. Brain Behav Immun 2014; 35: 58-63.
[http://dx.doi.org/10.1016/j.bbi.2013.08.013] [PMID: 24012647]
[47]
Filiano AJ, Xu Y, Tustison NJ, et al. Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour. Nature 2016; 535(7612): 425-9.
[http://dx.doi.org/10.1038/nature18626] [PMID: 27409813]
[48]
Moy SS, Nadler JJ, Perez A, et al. Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes Brain Behav 2004; 3(5): 287-302.
[http://dx.doi.org/10.1111/j.1601-1848.2004.00076.x] [PMID: 15344922]
[49]
Cohen H, Ziv Y, Cardon M, et al. Maladaptation to mental stress mitigated by the adaptive immune system via depletion of naturally occurring regulatory CD4+CD25+ cells. J Neurobiol 2006; 66(6): 552-63.
[http://dx.doi.org/10.1002/neu.20249] [PMID: 16555237]
[50]
Rattazzi L, Piras G, Ono M, Deacon R, Pariante CM, D’Acquisto F. CD4+ but not CD8+ T cells revert the impaired emotional behavior of immunocompromised RAG-1-deficient mice. Transl Psychiatry 2013; 3(7)e280
[http://dx.doi.org/10.1038/tp.2013.54] [PMID: 23838891]
[51]
Norris GT, Kipnis J. Immune cells and CNS physiology: microglia and beyond. J Exp Med 2019; 216(1): 60-70.
[http://dx.doi.org/10.1084/jem.20180199] [PMID: 30504438]
[52]
Louveau A, Herz J, Alme MN, et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci 2018; 21(10): 1380-91.
[http://dx.doi.org/10.1038/s41593-018-0227-9] [PMID: 30224810]
[53]
Louveau A, Filiano AJ, Kipnis J. Meningeal whole mount preparation and characterization of neural cells by flow cytometry. Curr Protoc Immunol 2018; 121(1)e50
[http://dx.doi.org/10.1002/cpim.50] [PMID: 30008983]
[54]
Mrdjen D, Pavlovic A, Hartmann FJ, et al. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease. Immunity 2018; 48(2): 380-395.e6.
[http://dx.doi.org/10.1016/j.immuni.2018.01.011] [PMID: 29426702]
[55]
Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 1988; 12(2): 123-37.
[http://dx.doi.org/10.1016/S0149-7634(88)80004-6] [PMID: 3050629]
[56]
Starkman BG, Sakharkar AJ, Pandey SC. Epigenetics-beyond the genome in alcoholism. Alcohol Res 2012; 34(3): 293-305.
[PMID: 23134045]
[57]
Bos N, Lefèvre T, Jensen AB, d’Ettorre P. Sick ants become unsociable. J Evol Biol 2012; 25(2): 342-51.
[http://dx.doi.org/10.1111/j.1420-9101.2011.02425.x] [PMID: 22122288]
[58]
Kazlauskas N, Klappenbach M, Depino AM, Locatelli FF. Sickness behavior in honey bees. Front Physiol 2016; 7: 261.
[http://dx.doi.org/10.3389/fphys.2016.00261] [PMID: 27445851]
[59]
Blum K, Oscar-Berman M, Bowirrat A, et al. 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 2012; 3(112)1000112
[PMID: 23336089]
[60]
Comings DE, Muhleman D, Gysin R. Dopamine D2 receptor (DRD2) gene and susceptibility to posttraumatic stress disorder: a study and replication. Biol Psychiatry 1996; 40(5): 368-72.
[http://dx.doi.org/10.1016/0006-3223(95)00519-6] [PMID: 8874837]
[61]
Petrulli JR, Kalish B, Nabulsi NB, Huang Y, Hannestad J, Morris ED. Systemic inflammation enhances stimulant-induced striatal dopamine elevation. Transl Psychiatry 2017; 7(3)e1076
[http://dx.doi.org/10.1038/tp.2017.18] [PMID: 28350401]
[62]
Rossier J, French ED, Rivier C, Ling N, Guillemin R, Bloom FE. Foot-shock induced stress increases beta-endorphin levels in blood but not brain. Nature 1977; 270(5638): 618-20.
[http://dx.doi.org/10.1038/270618a0] [PMID: 201864]
[63]
Akil H, Young E, Watson SJ, Coy DH. Opiate binding properties of naturally occurring N- and C-terminus modified beta-endorphins. Peptides 1981; 2(3): 289-92.
[http://dx.doi.org/10.1016/S0196-9781(81)80121-0] [PMID: 6272244]
[64]
Wybran J, Appelboom T, Famaey JP, Govaerts A. Suggestive evidence for receptors for morphine and methionine-enkephalin on normal human blood T lymphocytes. J Immunol 1979; 1233: 1068-70.
[65]
Plotnikoff NP, Miller GC. Enkephalins as immunomodulators. Int J Immunopharmacol 1983; 5(5): 437-41.
[http://dx.doi.org/10.1016/0192-0561(83)90020-6] [PMID: 6654540]
[66]
Gilman SC, Schwartz JM, Milner RJ, Bloom FE, Feldman JD. beta-Endorphin enhances lymphocyte proliferative responses. Proc Natl Acad Sci USA 1982; 79(13): 4226-30.
[http://dx.doi.org/10.1073/pnas.79.13.4226] [PMID: 6287475]
[67]
McCain HW, Lamster IB, Bilotta J. Modulation of human T-cell suppressor activity by beta endorphin and glycyl-L-glutamine. Int J Immunopharmacol 1986; 8(4): 443-6.
[http://dx.doi.org/10.1016/0192-0561(86)90130-X] [PMID: 2943688]
[68]
Wybran J. Enkephalins and endorphins as modifiers of the immune system: present and future. Fed Proc 1985; 44(1 Pt 1): 92-4.
[PMID: 2981735]
[69]
Johnson HM, Smith EM, Torres BA, Blalock JE. Regulation of the in vitro antibody response by neuroendocrine hormones. Proc Natl Acad Sci USA 1982; 79(13): 4171-4.
[http://dx.doi.org/10.1073/pnas.79.13.4171] [PMID: 6287470]
[70]
Smith R, Grossman A, Gaillard R, et al. Studies on circulating met-enkephalin and beta-endorphin: normal subjects and patients with renal and adrenal disease. Clin Endocrinol 1981; 15(3): 291-300.
[http://dx.doi.org/10.1111/j.1365-2265.1981.tb00668.x] [PMID: 6273029]
[71]
Vaswani KK, Richard CW III, Tejwani GA. Cold swim stress-induced changes in the levels of opioid peptides in the rat CNS and peripheral tissues. Pharmacol Biochem Behav 1988; 29(1): 163-8.
[http://dx.doi.org/10.1016/0091-3057(88)90290-0] [PMID: 3353422]
[72]
Smith EM, Morrill AC, Meyer WJ III, Blalock JE. Corticotropin releasing factor induction of leukocyte-derived immunoreactive ACTH and endorphins. Nature 1986; 321(6073): 881-2.
[http://dx.doi.org/10.1038/321881a0] [PMID: 3014342]
[73]
Cheĭdo MA, Gevorgian MM. Role of dopamine D1- and D2-receptors in the delta1-opioidergic immunostimulationVestn Ross Akad Med Nauk 2012; (5): 55-7.
[http://dx.doi.org/10.15690/vramn.v67i5.275] [PMID: 22856169]
[74]
Cheĭdo MA, Idova GV. Effect of opioid peptides on immunomodulation Ross Fiziol Zh Im I M Sechenova 1998; 84(4): 385-90.
[PMID: 9742618]
[75]
Williamson SA, Knight RA, Lightman SL, Hobbs JR. Effects of beta endorphin on specific immune responses in man. Immunology 1988; 65(1): 47-51.
[PMID: 2846433]
[76]
Ehrenpreis S. D-phenylalanine and other enkephalinase inhibitors as pharmacological agents: implications for some important therapeutic application. Subst Alcohol Actions Misuse 1982; 3(4): 231-9.
[http://dx.doi.org/10.3727/036012982816952099] [PMID: 6301083]
[77]
Thanawala V, Kadam VJ, Ghosh R. Enkephalinase inhibitors: potential agents for the management of pain. Curr Drug Targets 2008; 9(10): 887-94.
[http://dx.doi.org/10.2174/138945008785909356] [PMID: 18855623]
[78]
Ehrenpreis S. D-phenylalanine and other enkephalinase inhibitors as pharmacological agents: implications for some important therapeutic application. Acupunct Electrother Res 1982; 7(2-3): 157-72.
[http://dx.doi.org/10.3727/036012982816952099] [PMID: 6128872]
[79]
Nagarjun S, Dhadde SB, Veerapur VP, Thippeswamy BS, Chandakavathe BN. Ameliorative effect of chromium-d-phenylalanine complex on indomethacin-induced inflammatory bowel disease in rats. Biomed Pharmacother 2017; 89: 1061-6.
[http://dx.doi.org/10.1016/j.biopha.2017.02.042] [PMID: 28292014]
[80]
Febo M, Blum K, Badgaiyan RD, et al. Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z. PLoS One 2017; 12(4)e0174774
[http://dx.doi.org/10.1371/journal.pone.0174774] [PMID: 28445527]
[81]
Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 1991; 48(7): 648-54.
[http://dx.doi.org/10.1001/archpsyc.1991.01810310066012] [PMID: 2069496]
[82]
Payer D, Williams B, Mansouri E, et al. Corticotropin-releasing hormone and dopamine release in healthy individuals. Psychoneuroendocrinology 2017; 76: 192-6.
[http://dx.doi.org/10.1016/j.psyneuen.2016.11.034] [PMID: 27951520]
[83]
Cabib S, Puglisi-Allegra S. The mesoaccumbens dopamine in coping with stress. Neurosci Biobehav Rev 2012; 36(1): 79-89.
[http://dx.doi.org/10.1016/j.neubiorev.2011.04.012] [PMID: 21565217]
[84]
Pan WH, Yang SY, Lin SK. Neurochemical interaction between dopaminergic and noradrenergic neurons in the medial prefrontal cortex. Synapse 2004; 53(1): 44-52.
[http://dx.doi.org/10.1002/syn.20034] [PMID: 15150740]
[85]
Roy-Byrne P, Arguelles L, Vitek ME, et al. Persistence and change of PTSD symptomatology-a longitudinal co-twin control analysis of the Vietnam Era Twin Registry. Soc Psychiatry Psychiatr Epidemiol 2004; 39(9): 681-5.
[http://dx.doi.org/10.1007/s00127-004-0810-0] [PMID: 15672287]
[86]
Cabana-Domínguez J, Shivalikanjli A, Fernàndez-Castillo N, Cormand B. Genome-wide association meta-analysis of cocaine dependence: Shared genetics with comorbid conditions. Prog Neuropsychopharmacol Biol Psychiatry 2019; 94109667
[http://dx.doi.org/10.1016/j.pnpbp.2019.109667] [PMID: 31212010]
[87]
Szutorisz H, DiNieri JA, Sweet E, et al. Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation. Neuropsychopharmacology 2014; 39(6): 1315-23.
[http://dx.doi.org/10.1038/npp.2013.352]
[88]
Auxéméry Y. Posttraumatic stress disorder (PTSD) as a consequence of the interaction between an individual genetic susceptibility, a traumatogenic event and a social context Encephale 2012; 38(5): 373-80.
[PMID: 23062450]
[89]
Zhang K, Wang L, Cao C, et al. A DRD2/ANNK1-COMT interaction, consisting of functional variants, confers risk of post-traumatic stress disorder in traumatized chinese. Front Psychiatry 2018; 9: 170.
[http://dx.doi.org/10.3389/fpsyt.2018.00170] [PMID: 29760667]
[90]
Brown LA, Gallagher T, Petersen J, Benhamou K, Foa EB, Asnaani A. Does CBT for anxiety-related disorders alter suicidal ideation? Findings from a naturalistic sample. J Anxiety Disord 2018; 59: 10-6.
[http://dx.doi.org/10.1016/j.janxdis.2018.08.001] [PMID: 30107264]
[91]
Wildlife USF. FWS Critical Incident Stress Management Handbook. United States: U.S. Fish & Wildlife Service 2019.
[92]
Smith BH, Higgins C, Baldacchino A, Kidd B, Bannister J. Substance misuse of gabapentin. J R Coll Gen Pract 2012; 62(601): 406-7.
[http://dx.doi.org/10.3399/bjgp12X653516]
[93]
McLaughlin T, Blum K, Oscar-Berman M, et al. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy. J Behav Addict 2015; 4(2): 106-15.
[http://dx.doi.org/10.1556/2006.4.2015.008] [PMID: 26132915]
[94]
McLaughlin T, Blum K, Oscar-Berman M, et al. 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 2015; 1(1): 24-35.
[http://dx.doi.org/10.17756/jrds.2015-006] [PMID: 26065033]
[95]
McLaughlin T, Febo M, Badgaiyan RD, et al. 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 2016; 2(1): 3-13.
[http://dx.doi.org/10.17756/jrdsas.2016-022] [PMID: 28210713]
[96]
Maxwell J. Ethical, legal, social, and policy issues in the use of genomic technology by the US military. J Biosci 2014; 1(3): 244-80.
[97]
Evans NG, Moreno JD. Yesterday’s war; tomorrow’s technology: peer commentary on ‘Ethical, legal, social and policy issues in the use of genomic technologies by the US military’. J Law Biosci 2014; 2(1): 79-84.
[http://dx.doi.org/10.1093/jlb/lsu030] [PMID: 27774182]
[98]
Savulescu J. Science wars-How much risk should soldiers be exposed to in military experimentation? J Law Biosci 2015; 2(1): 99-104.
[http://dx.doi.org/10.1093/jlb/lsv006] [PMID: 27774185]
[99]
Baumann TK. Proxy consent and a national DNA databank: an unethical and discriminatory combination. Iowa Law Rev 2001; 86(2): 667-701.
[PMID: 16184651]
[100]
Pereira S, Hsu RL, Islam R, et al. MilSeq Project. Airmen and health-care providers’ attitudes toward the use of genomic sequencing in the US Air Force: findings from the MilSeq Project. Genet Med 2020; 22(12): 2003-10.
[http://dx.doi.org/10.1038/s41436-020-0928-9] [PMID: 32807975]
[101]
Blum K, Gondré-Lewis MC, Baron D, et al. Introducing precision addiction management of reward deficiency syndrome, the construct that underpins all addictive behaviors. Front Psychiatry 2018; 9: 548.
[http://dx.doi.org/10.3389/fpsyt.2018.00548] [PMID: 30542299]
[102]
Thanos PK, Hamilton J, O’Rourke JR, et al. Dopamine D2 gene expression interacts with environmental enrichment to impact lifespan and behavior. Oncotarget 2016; 7(15): 19111-23.
[http://dx.doi.org/10.18632/oncotarget.8088] [PMID: 26992232]
[103]
Blum K, Chen TJ, Morse S, et al. Overcoming qEEG abnormalities and reward gene deficits during protracted abstinence in male psychostimulant and polydrug abusers utilizing putative dopamine D2 agonist therapy: part 2. Postgrad Med 2010; 122(6): 214-26.
[http://dx.doi.org/10.3810/pgm.2010.11.2237] [PMID: 21084796]
[104]
Kjaer TW, Bertelsen C, Piccini P, Brooks D, Alving J, Lou HC. Increased dopamine tone during meditation-induced change of consciousness. Brain Res Cogn Brain Res 2002; 13(2): 255-9.
[http://dx.doi.org/10.1016/S0926-6410(01)00106-9] [PMID: 11958969]
[105]
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: 282-97.
[http://dx.doi.org/10.1016/j.neubiorev.2016.05.033] [PMID: 27246519]

© 2024 Bentham Science Publishers | Privacy Policy