How Psychogenetics &
Nutrigenomics Began
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The Kenneth Blum, PhD Life Story: A man seeking truth while reaching for the Stars.
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References
1. Blum K. The effect of dopamine and other catecholamines on neuromuscular transmission. Arch Int Pharmacodyn Ther. 1969 :181(2):297-306.
2. Blum K, Seifter E, Seifter J. The pharmacology of d- and l-carnitine and d- and l-acetylcarnitine. Comparison with choline and acetylcholine. J Pharmacol Exp Ther. 1971 :178(2):331-8.
3. Geller I. Ethanol preference in the rat ask a function of photoperiod. Science. 1971;173(995):456-9.
4. Reiter RJ, Blum K, Wallace JE, Merritt JH. Pineal gland: evidence for an influence on ethanol preference in male Syrian hamsters.Comp Biochem Physiol A Comp Physiol. 1974 ;47(1):11-6.
5. Reiter RJ, Blum K, Wallace JE, Merritt JH. Effect of the pineal gland on alcohol consumption by congenitally blind male rats.Q J Stud Alcohol. 1973;34(3):937-9.
6. Blum K, Merritt JH, Reiter RJ, Wallace JE. A possible relationship between the pineal gland and ethanol preference in the rat.Curr Ther Res Clin Exp. 1973 ;15(1):25-30.
7. Davis VE, Walsh MJ. Alcohol, amines, and alkaloids: a possible biochemical basis for alcohol addiction.Science. 1970;167(920):1005-7.
8. Cohen G, Collins M. Alkaloids from catecholamines in adrenal tissue: possible role in alcoholism.Science. 1970;167(926):1749-51.
9. Blum K (Editor) "Alchol and Opiates: Common Neurochemical and Behavioral Mechanisms . 1978 Academic Press, New York.
10. Blum K, Futterman S, Wallace JE, Schwertner HA. Naloxone-induced inhibition of ethanol dependence in mice. Nature. 1977;265(5589):49-51
11. 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
12. Blum K, Eubanks JD, Wallace JE, Schwertner HA. Suppression of ethanol withdrawal by dopamine. Experientia. 1976;32(4):493-5.
13. Blum K, Wallace JE, Schwerter HA, Eubanks JD. Morphine suppression of ethanol withdrawal in mice. Experientia. 1976;32(1):79-82.
14. Blum K, Hamilton MG, Meyer EK, Hirst M, Marshall A. Isoquinoline alkaloids as possible regulators of alcohol addiction. Lancet. 1977;1(8015):799-800.
15. Blum K. Narcotic antagonism of seizures induced by a dopamine-derived tetrahydroisoquinoline alkaloid. Experientia. 1988;44(9):751-3.
16. Marshall A, Hirst M, Blum K. Analgesic effects of 3-carboxysalsolinol alone and in combination with morphine. Experientia. 1977;33(6):754-5.
17. Myers RD, Melchior CL. Alcohol drinking: abnormal intake caused by tetrahydropapaveroline in brain. Science. 1977;196(4289):554-6.
18. Pert CB, Snyder SH. Opiate receptor: demonstration in nervous tissuue. Science. 1973;179(77):1011-4.
19. Myers RD. Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms. Experientia. 1989;45(5):436-43.
20. Kosterlitz HW, Hughes J. Peptides with morphine-like action in the brain.Br J Psychiatry. 1977;130:298-304.
21. Foppoli C, Coccia R, Blarzino C, Cini C, Rosei MA. Tetrahydroisoquinoline derivatives of enkephalins: synthesis and properties. Biochem Pharmacol. 2002 May 15;63(10):1885-92.
22. Blum K, Wallace JE, Briggs AH, Trachtenberg MC. Evidence for the importance of the "genotype" theory in alcohol seeking behavior: a commentary. Alcohol Drug Res. 1985-1986;6(6):455-61.
23. Blum K, Elston SF, DeLallo L, Briggs AH, Wallace JE. Ethanol acceptance as a function of genotype amounts of brain [Met]enkephalin.Proc Natl Acad Sci U S A. 1983;80(21):6510-2.
24. Racz I, Schrmann B, Karpushova A, Reuter M, Cichon S, Montag C, Frst R, Schtz C, Franke PE, Strohmaier J, Wienker TF, Terenius L, Osby U, Gunnar A, Maier W, Bilkei-Gorz A, Nthen M, Zimmer A. The opioid peptides enkephalin and beta-endorphin in alcohol dependence. Biol Psychiatry. 2008;64(11):989-97.
25. Dai X, Thavundayil J, Gianoulakis C. Differences in the peripheral levels of beta-endorphin in response to alcohol and stress as a function of alcohol dependence and family history of alcoholism. Alcohol Clin Exp Res. 2005;29(11):1965-75.
26. Blum K. "Handbook on Abusable Drugs "1984, Gardner press, New York, New York.
27. Blum K, Briggs AH, Elston SF, DeLallo L, .
Sheridan PJ, Sar M. Reduced leucine-enkephalin--like immunoreactive substance in hamster basal ganglia after long-term ethanol exposureScience. 1982;216(4553):1425-7.
28. Przew?ocki R, Hllt V, Duka T, Kleber G, Gramsch C, Haarmann I, Herz A. Long-term morphine treatment decreases endorphin levels in rat brain and pituitary.Brain Res. 1979 5;174(2):357-61.
29. Sforzo GA, Seeger TF, Pert CB, Pert A, Dotson CO. In vivo opioid receptor occupation in the rat brain following exercise. Med Sci Sports Exerc. 1986 18(4):380-4.
30. Sacharczuk M, Juszczak G, Sliwa AT, Tymosiak-Zielinska A, Lisowski P, Jaszczak K, Pluta R, Lipkowski A, Sadowski B, Swiergiel AH. Differences in ethanol drinking between mice selected for high and low swim stress-induced analgesia. Alcohol. 2008;42(6):487-92.
31. Donzelle G, Bernard L, Deumier R, Lacome M, Barre M, Lanier M, Mourtada MB. Curing trial of complicated oncologic pain by D-phenylalanine Anesth Analg (Paris). 1981;38(11-12):655-8.
32. Marcello F, Grazia SM, Sergio M, Federigo S. Pharmacological "enkephalinase" inhibition in man.Adv Exp Med Biol. 1986;198 Pt B:153-60.
33. Blum K, Briggs AH, Trachtenberg MC, Delallo L, Wallace JE. Enkephalinase inhibition: regulation of ethanol intake in genetically predisposed mice.Alcohol. 1987;4(6):449-56.
34. Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004;150(1):111-22.
35. Attenburrow MJ, Odontiadis J, Murray BJ, Cowen,PJ Franklin M. Chromium treatment decreases the sensitivity of 5-HT2A receptors. Psychopharmacology (Berl). 2002;159(4):432-6.
36. Blum K, Trachtenberg MC, Elliott CE, Dingler ML, Sexton RL, Samuels AI, Cataldie L. Enkephalinase inhibition and precursor amino acid loading improves inpatient treatment of alcohol and polydrug abusers: double-blind placebo-controlled study of the nutritional adjunct SAAVE. Alcohol. 1988;5(6):481-93
37. Trachtenberg MC, Blum K. Improvement of cocaine-induced neuromodulator deficits by the neuronutrient Tropamine.J Psychoactive Drugs. 1988 Jul-Sep;20(3):315-31.
38. Blum K, Trachtenberg ML, and Cook DW. Neuronutrient effects on weight loss in carbohydrate bingers: An open clinical trial. Curr Ther Res. 1990b;48(2):21723
39. Blum K , Kozlowski GP. Ethanol and neurotransmitter interactions: a cascade model of reward. In: Ollat H, Parvez S, Parvez H. eds. Alchol and Behavior, Uterecht,The Netherlands:VSP Press: 1990a:131-149.
40. Wise RA, Bozarth MA. Brain substrates for reinforcement and drug self-administration. Prog Neuropsychopharmacol. 1981;5(5-6):467-74.
41. Egeland JA. A genetic study of manic-depressive disorder among the old order Amish of Pennsylvania. Pharmacopsychiatry. 1988 Mar;21(2):74-5.
42. Bunzow JR, Van Tol HH, Grandy DK, Albert P, Salon J, Christie M, Machida CA, Neve KA, Civelli O. Cloning and expression of a rat D2 dopamine receptor cDNA.Nature. 1988 Dec 22-29;336(6201):783-7.
43. Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Jagadeeswaran P, Nogami H, Briggs AH, Cohn JB. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA. 1990;263(15):2055-60.
44. Gordis E, Tabakoff B, Goldman D, Berg K. Finding the gene(s) for alcoholism. JAMA. 1990 Apr 18;263(15):2094-5.
45. Uhl GR, Persico AM, Smith SS. Current excitement with D2 dopamine receptor gene alleles in substance abuse.Arch Gen Psychiatry. 1992 Feb;49(2):157-60.
46. Bolos AM, Dean M, Lucas-Derse S, Ramsburg M, Brown GL, Goldman D. Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism.JAMA. 1990 Dec 26;264(24):3156-60.
47. Xu K, Lichtermann D, Lipsky RH, Franke P, Liu X, Hu Y, Cao L, Schwab SG, Wildenauer DB, Bau CH, Ferro E, Astor W, Finch T, Terry J, Taubman J, Maier W, Goldman D. Association of specific haplotypes of D2 dopamine receptor gene with vulnerability to heroin dependence in 2 distinct populations. Arch Gen Psychiatry. 2004 Jun;61(6):597-606.
48. Yang BZ, Kranzler HR, Zhao H, Gruen JR, Luo X, Gelernter J. Haplotypic variants in DRD2, ANKK1, TTC12, and NCAM1 are associated with comorbid alcohol and drug dependence. Alcohol Clin Exp Res. 2008 Dec;32(12):2117-27.
49. Comings DE, Comings BG, Muhleman D, Dietz G, Shahbahrami B, Tast D, Knell E, Kocsis P, Baumgarten R, Kovacs BW, et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders.JAMA. 1991 Oct 2;266(13):1793-800.
50. Gelernter J, O'Malley S, Risch N, Kranzler HR, Krystal J, Merikangas K, Kennedy JL, Kidd KK. No association between an allele at the D2 dopamine receptor gene (DRD2) and alcoholism.JAMA. 1991 Oct 2;266(13):1801-7.
51. Blum K (with James Payne) " Alcohol and the Addictive Brain" The Free Press ( Division of Macmillan Inc) New York, London, 1991.
52. 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 Jul;48(7):648-54.
53. Thompson J, Thomas N, Singleton A, Piggott M, Lloyd S, Perry EK, Morris CM, Perry RH, Ferrier IN, Court JA. D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics. 1997 Dec;7(6):479-84.
54. Abdolmaleky HM, Thiagalingam S, Wilcox M. Genetics and epigenetics in major psychiatric disorders: dilemmas, achievements, applications, and future scope. Am J Pharmacogenomics. 2005;5(3):149-60.
55. Blum K, Braverman ER, Wu S, Cull JG, Chen TJ, Gill J, Wood R, Eisenberg A, Sherman M, Davis KR, Matthews D, Fischer L, Schnautz N, Walsh W, Pontius AA, Zedar M, Kaats G, Comings DE. Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB).Mol Psychiatry. 1997 May;2(3):239-46.
56. Chen TJH , Blum K, Kaats, G , Braverman ER et al. 2007. Chromium Picolinate a putative anti-obesity nutrient induces changes in body composition as a function of the Taq 1 dopamine D2 receptor polymorphisms in a randomized double-blind placebo controlled study. Gene Therapy Mol. Biol. 11: 161-170.
57. Downs BW, Chen AL, Chen TJ, Waite RL, Braverman ER, Kerner M, Braverman D, Rhoades P, Prihoda TJ, Palomo T, Oscar-Berman M, Reinking J, Blum SH, DiNubile NA, Liu HH, Blum K. Nutrigenomic targeting of carbohydrate craving behavior: can we manage obesity and aberrant craving behaviors with neurochemical pathway manipulation by Immunological Compatible Substances (nutrients) using a Genetic Positioning System (GPS) Map?Med Hypotheses. 2009 Sep;73(3):427-34.
58. Boundy VA, Pacheco MA, Guan W, Molinoff PB Agonists and antagonists differentially regulate the high affinity state of the D2L receptor in human embryonic kidney 293 cells.Mol Pharmacol. 1995 Nov;48(5):956-64.
59. Dackis CA, Gold MS. New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci Bio Rev. 1985; 9(3):469-477
60. Blum K noble EP (Eds.) "Handbook o f Psychiatric Genetics ." 1996. CRC Press ,Boca Raton , FL.
61. Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Cull JG, Comings DE. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome.J R Soc Med. 1996 Jul;89(7):396-400.
62. Blum K, Cull JG, Barverman ER, Comings DE. Reward Deficiency Syndrome .The American Scientist. 1996; 84(2) :132-145.
63. Blum K, Cull JG, Chen TJH, Garcia-Swan S, Holder JM, Wood R, Braveramn Er, Buci LR, Trachtenberg MC. Clinical evidence for effectiveness of PhenCal in maintaining weight loss in an open -label controlled 2-year study. Current Therap. Res. 58 (10) 745.
64. 1st Conference on Reward Deficiency Syndrome: Genetic Antecedents and Clinical Pathways. San Francisco, California, USA. November 12-13, 2000. Abstracts.[No authors listed]Mol Psychiatry. 2001 Feb;6(1 Suppl 1):S1-8.
65. Pfaffly J, Michaelides M, Wang GJ, Pessin JE, Volkow ND, Thanos PK. SLeptin increases striatal dopamine D2 receptor binding in leptin-deficient obese (ob/ob) mice.Synapse. 2010 Jul;64(7):503-10.
66. Asensio S, Romero MJ, Romero FJStriatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later. Synapse. 2010 May;64(5):397-402.
67. Blum K, Chen TJ, Meshkin B, Downs BW, Gordon CA, Blum S, Mengucci JF, Braverman ER, Arcuri V, Varshavskiy M, Deutsch R, Martinez-Pons M. Reward deficiency syndrome in obesity: a preliminary cross-sectional trial with a Genotrim variant. Adv Ther. 2006 Nov-Dec;23(6):1040-51.
68. Chen TJ, Blum K, Payte JT, Schoolfield J, Hopper D, Stanford M, Braverman ER. Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy. Med Hypotheses. 2004;63(3):538-48.
69. Blum K, Chen AL, Chen TJ, Rhoades P, Prihoda TJ, Downs BW, Waite RL, Williams L, Braverman ER, Braverman D, Arcuri V, Kerner M, Blum SH, Palomo T. LG839: anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome. Adv Ther. 2008;25(9):894-913
70. Blum K, Chen ALC, Chen TJH, et al. Putative targeting of dopamine D2 receptor function in Reward deficiency Syndrome (RDS) by Synaptamine Complex Variant (KB220): clinical trial showing anti-anxiety effects. Gene Therapy Mol. Biol. 2009;13: (in press)
71. Blum K, Chen TJH, Chen ALC, Rhoades P, Prihoda TJ, Downs BW, Bagchi D, Bagchi M, Blum SH, Williams L, Braverman, ER, Kerner M, Waite RL, Quirk B, White L, R Reinking J. Dopamine D2 Receptor Taq A1 allele predicts treatment compliance of LG839 in a subset analysis of pilot study in the Netherlands .Gene Therapy Mol. Biol. 2008;12:129-140
72. Blum K, Chen TJ, Chen AL, Madigan M, Downs BW, Waite RL, Braverman ER, Kerner M, Bowirrat A, Giordano J, Henshaw H, Gold MS. Do dopaminergic gene polymorphisms affect mesolimbic reward activation of music listening response? Therapeutic impact on Reward Deficiency Syndrome (RDS). Med Hypotheses. 2010 Mar;74(3):513-20
73. Blum K, Ho CK, Chen AL, Fulton M, Fulton B, Westcott WL, Reinl G, Braverman ER, Dinubile N, Chen TJ. The H-Wave((R)) Device Induces NODependent Augmented Microcirculation and Angiogenesis, Providing Both Analgesia and Tissue Healing in Sports Injuries.Phys Sportsmed. 2008 Dec;36(1):103-14.
74. Stice E, Spoor S, Bohon C, Small DM. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele.Science. 2008 Oct 17;322(5900):449-52.
75. Stice E, Yokum S, Bohon C, Marti N, Smolen A. Reward circuitry responsivity to food predicts future increases in body mass: moderating effects of DRD2 and DRD4. Neuroimage. 2010 May 1;50(4):1618-25.
76. Blum K, Chen TJ, Downs BW, Bowirrat A, Waite RL, Braverman ER, Madigan M, Oscar-Berman M, DiNubile N, Stice E, Giordano J, Morse S, Gold M. Neurogenetics of dopaminergic receptor supersensitivity in activation of brain reward circuitry and relapse: proposing "deprivation-amplification relapse therapy" (DART).Postgrad Med. 2009 Nov;121(6):176-96.
77. Davis LM, Michaelides M, Cheskin LJ, Moran TH, Aja S, Watkins PA, Pei Z, Contoreggi C, McCullough K, Hope B, Wang GJ, Volkow ND, Thanos PK. Bromocriptine administration reduces hyperphagia and adiposity and differentially affects dopamine D2 receptor and transporter binding in leptin-receptor-deficient Zucker rats and rats with diet-induced obesity.Neuroendocrinology. 2009;89(2):152-62.
78. Davis CA, Levitan RD, Reid C, Carter JC, Kaplan AS, Patte KA, King N, Curtis C, Kennedy JL. Dopamine for "wanting" and opioids for "liking": a comparison of obese adults with and without binge eating.Obesity (Silver Spring). 2009 Jun;17(6):1220-5.
79. Bowirrat A, Oscar-Berman M. Relationship between dopaminergic neurotransmission, alcoholism, and Reward Deficiency syndrome. Am J Med Genet B Neuropsychiatr Genet. 2005 Jan 5;132B(1):29-37.
80. Comings DE, Blum K. Reward deficiency syndrome: genetic aspects of behavioral disorders. Prog Brain Res. 2000;126:325-41
81. Miller DK and Blum K "Overload" : ADHD and the Addictive Brain. 1996 and 2000 (2nd printing) Hope Press, Duarte, California,.
82. Blum K, Chen AL, Chen TJ, Braverman ER, Reinking J, Blum SH, Cassel K, Downs BW, Waite RL, Williams L, Prihoda TJ, Kerner MM, Palomo T, Comings DE, Tung H, Rhoades P, Oscar-Berman M. 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 Nov 12;5:24
83. Blum K, Chen TJH, Morse S, et al. Overcoming qEEG Abnormalities and Reward Gene Deficits During Protracted Abstinence In Psychostimulant Abusers Utilizing Putative Dopamine D2 Agonist Therapy. Postgraduate Medicine.(in Press)
84. Bolton JL, Marioni RE, Deary IJ, Harris SE, Stewart MC, Murray GD, Fowkes FG, Price JF. Association Between Polymorphisms of the Dopamine Receptor D2 and Catechol-o-Methyl Transferase Genes and Cognitive Function. Behav Genet. 2010 Jun 22.
85. DeFrance JF, Hymel C, Trachtenberg MC, Ginsberg LD, Schweitzer FC, Estes S, Chen TJ, Braverman ER, Cull JG, Blum K. Enhancement of attention processing by Kantroll in healthy humans: a pilot study. Clin Electroencephalogr. 1997 Apr;28(2):68-75.
86. De Steno DA, Schmauss C. A role for dopamine D2 receptors in reversal learning Neuroscience. 2009 Aug 4;162(1):118-27.
87. Miller D, Manka M, Miller M, et al. Acute Intravenous Synaptamine Complex [KB220]
TM
Variant "Normalizes" Abnormal Neurological Activity in Protracted Abstinence of Alcohol and Opiate Patients Using Quantitative Electroencephalographic (QEEG) and Neurotransmitter Genetic Analysis: Pilot Two Case Reports. Postgraduate Medicine (in Press)
88. Blum K, Chen TJH, Downs BW, et al. Synaptamine (SG8839) An Amino-Acid Enkephalinase Inhibition Nutraceutical Improves Recovery of Alcoholics, A Subtype of Reward Deficiency Syndrome (RDS). Trends in Applied Sciences Research. 2007;2(2):132-138.
89. Schoenthaler SJ, Bier ID, Young K, Nichols D, Jansenns S. The effect of vitamin-mineral supplementation on the intelligence of American schoolchildren: a randomized, double-blind placebo-controlled trial.J Altern Complement Med. 2000 Feb;6(1):19-29.
90. Schoenthaler SJ, Bier ID. The effect of vitamin-mineral supplementation on juvenile delinquency among American schoolchildren: a randomized, double-blind placebo-controlled trial.
91. J Altern Complement Med. 2000 Feb;6(1):7-17.
92. Schoenthaler SJ, Bier ID. Vitamin-mineral intake and intelligence: a macrolevel analysis of randomized controlled trials.J Altern Complement Med. 1999 Apr;5(2):125-34.
93. Blum K, Giordano J, Morse S, Liu Y, Tan Jai, Bowirrat A, Smolen A, Waite RL, Downs W, Madigan M, Kerner M, Fornari F, Stice E, Braverman E, Miller D, Bailey JA. Genetic Addiction Risk Score(GARS) analysis: exploratory development of polymorphic risk alleles. International J. Omics Biotechnology (in press).
94. Conner BT, Hellemann GS, Ritchie TL, Noble .EP. Genetic, personality, and environmental predictors of drug use in adolescents JSubst Abuse Treat. 2010 Mar;38(2):178-90.
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Dr. Blum and Dr. Waite advocated a non-specific "healthy diet" and non-specific regular exercise to accompany a regimen of taking Synaptose
TM
, the nutrigenomic neuroadaptogen they developed based on Dr. Blum's many years of research to increase the endogenous production of Dopamine and reduce negative Reward Deficiency Syndrome behaviors. The scientific evidence they have thus far accumulated, they say, demonstrates that Synaptose
TM
changes the plasticity of the brain synapses while balancing the endogenous neurotransmitters, positively affecting the Brain Reward Cascade.
