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Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine Haile CN; Kosten TR; Kosten TAAm J Drug Alcohol Abuse 2009[]; 35 (3): 161-77BACKGROUND: Pharmacogenetics uses genetic variation to predict individual differences in response to medications and holds much promise to improve treatment of addictive disorders. OBJECTIVES: To review how genetic variation affects responses to cocaine, amphetamine, and methamphetamine and how this information may guide pharmacotherapy. METHODS: We performed a cross-referenced literature search on pharmacogenetics, cocaine, amphetamine, and methamphetamine. RESULTS: We describe functional genetic variants for enzymes dopamine-beta-hydroxylase (DbetaH), catechol-O-methyltransferase (COMT), and dopamine transporter (DAT1), dopamine D4 receptor, and brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP; C-1021T) in the DbetaH gene is relevant to paranoia associated with disulfiram pharmacotherapy for cocaine addiction. Individuals with variable number tandem repeats (VNTR) of the SLC6A3 gene 3'-untranslated region polymorphism of DAT1 have altered responses to drugs. The 10/10 repeat respond poorly to methylphenidate pharmacotherapy and the 9/9 DAT1 variant show blunted euphoria and physiological response to amphetamine. COMT, D4 receptor, and BDNF polymorphisms are linked to methamphetamine abuse and psychosis. CONCLUSIONS: Disulfiram and methylphenidate pharmacotherapies for cocaine addiction are optimized by considering polymorphisms affecting DbetaH and DAT1 respectively. Altered subjective effects for amphetamine in DAT1 VNTR variants suggest a 'protected' phenotype. SCIENTIFIC SIGNIFICANCE: Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment.|Amphetamine-Related Disorders/*drug therapy/genetics[MESH]|Amphetamine/adverse effects[MESH]|Cocaine-Related Disorders/*drug therapy/genetics[MESH]|Disulfiram/adverse effects/therapeutic use[MESH]|Dopamine Uptake Inhibitors/therapeutic use[MESH]|Enzyme Inhibitors/adverse effects/therapeutic use[MESH]|Humans[MESH]|Methamphetamine/adverse effects[MESH]|Methylphenidate/therapeutic use[MESH]|Pharmacogenetics/*methods[MESH]|Polymorphism, Single Nucleotide[MESH] |
