Alcohol

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Ethnicity & A118G Allele Frequency • Based on multiple studies, allele frequencies differ markedly across ethnicities for the A118G SNP in the mu opioid receptor gene. It arose after the out-of-Africa migration. • Crowley et al, 2003 • Gelernter et al, 1999 • Tan et al, 2003 • Bart et al, 2004 ETHNICITY f(G) ETHNICITY f(G) African 1% Koreans 31% African- 3% Chinese 35% American Swedish 17% Malaysian 45% Europeanorigin US 15% Indian 47%
<strong>Alcohol</strong> effects by genotype 50 45 40 35 30 25 20 15 10 5 0 AA allele AG allele 0.02 0.04 0.06 Breath <strong>Alcohol</strong> Concentration
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The Path to Genomic Medicine For Ad
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Use Use Use Use Use Abuse (declarat
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Possible Changes • Addiction inst
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Addiction: Loss of control • Jean
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Possible Families of Risk Factors
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Response • Genetically influenced
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Drugs of Abuse all Activate Reward
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Effects of Drugs on Dopamine Levels
Page 17 and 18:
Relationship between Cue-Induced De
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“Unseen” Reward Cues activate a
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Alcoholism: FDA Approved Medication
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Alcohol - Beverage Condition Cingul
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Baclofen blunts Amygdala Connectivi
Page 28 and 29:
Alcohol reward Sedating drug, facil
Page 30 and 31: True Translational Story: Naltrexon
Page 32: Naltrexone decreases Alcohol prefer
Page 38 and 39: Ethanol Responses Saline 80 70 60 5
Page 40 and 41: Naltrexone Concurrently Antagonizes
Page 42 and 43: Brain Reward System Nucleus Accumbe
Page 44 and 45: Dopamine Opioid Antagonism Dopamine
Page 46 and 47: Propose an RCT of an opiate antagon
Page 48 and 49: Naltrexone Affinity at Opioid Recep
Page 50 and 51: Receptor Blockade with Naltrexone i
Page 52 and 53: Post-Docs Tom Aronson, MD Joseph Vo
Page 54 and 55: Pharmacological Treatments for Alco
Page 56 and 57: Days Drinking 1.0 0.8 0.6 0.4 0.2 0
Page 58 and 59: Alcohol Relapse A. coming to treatm
Page 60 and 61: Rates of Never Relapsing According
Page 62 and 63: Blood Alcohol levels (g/dl) 0.1 0.0
Page 64 and 65: Studies supporting efficacy Studies
Page 66 and 67: Baseline Craving Scores % Days Heav
Page 68 and 69: Baseline b-Endorphin Levels in Low-
Page 70 and 71: Key effect: Sensitivity of Endogeno
Page 72 and 73: BAES Stimulation Scores Among FH+ a
Page 74 and 75: Human Mu Opioid Receptor Gene PROMO
Page 76 and 77: Alcohol effects by genotype 50 45 4
Page 78 and 79: Lotsch et al, 2006
Page 82 and 83: Subjective “high” in Naltrexone
Page 84 and 85: OPRM1 A118G and Alcoholism Bart et
Page 86 and 87: COMBINE Study • N = 1383; 9 rando
Page 88 and 89: Rhesus model Ortholog of A118G alle
Page 90 and 91: Results: Heavy Drinking Days 30 75
Page 92 and 93: Endophenotype Endorphin Dependent A
Page 94 and 95: Medications • Nicotine Nicotine p
Page 96 and 97: FOR MORE INFORMATION http://www.med
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Alcohol

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