Pharmacogenetic Treatments for Drug Addiction: Cocaine, Amphetamine and Methamphetamine Export

@article{citeulike:4597418, abstract = {<i>Background</i>: Pharmacogenetics uses genetic variation to predict individual differences in response to medications and holds much promise to improve treatment of addictive disorders. <i>Objectives</i>: To review how genetic variation affects responses to cocaine, amphetamine, and methamphetamine and how this information may guide pharmacotherapy. <i>Methods</i>: We performed a cross-referenced literature search on pharmacogenetics, cocaine, amphetamine, and methamphetamine. <i>Results</i>: We describe functional genetic variants for enzymes dopamine-beta-hydroxylase (D\&b.beta;H), catechol-<i>O</i>-methyltransferase (COMT), and dopamine transporter (DAT1), dopamine D4 receptor, and brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP; C-1021T) in the D\&b.beta;H gene is relevant to paranoia associated with disulfiram pharmacotherapy for cocaine addiction. Individuals with variable number tandem repeats (VNTR) of the <i>SLC6A3</i> gene 3\&prime;-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. <i>Conclusions</i>: Disulfiram and methylphenidate pharmacotherapies for cocaine addiction are optimized by considering polymorphisms affecting D\&b.beta;H and DAT1 respectively. Altered subjective effects for amphetamine in DAT1 VNTR variants suggest a ‘protected’ phenotype. <i>Scientific Significance</i>: Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment.}, author = {Haile, Colin N. and Kosten, Thomas R. and Kosten, Therese A.}, citeulike-article-id = {4597418}, citeulike-linkout-0 = {http://dx.doi.org/10.1080/00952990902825447}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19462300}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19462300}, doi = {10.1080/00952990902825447}, journal = {The American Journal of Drug and Alcohol Abuse}, keywords = {addiction, cocaine, methamphetamine, pharmacogenetics}, number = {3}, pages = {161--177}, posted-at = {2009-05-22 15:34:37}, priority = {2}, publisher = {Informa Healthcare}, title = {Pharmacogenetic Treatments for Drug Addiction: Cocaine, Amphetamine and Methamphetamine}, url = {http://dx.doi.org/10.1080/00952990902825447}, volume = {35}, year = {2009} }

TY - JOUR ID - citeulike:4597418 L3 - citeulike-article-id:4597418 N2 - <i>Background</i>: Pharmacogenetics uses genetic variation to predict individual differences in response to medications and holds much promise to improve treatment of addictive disorders. <i>Objectives</i>: To review how genetic variation affects responses to cocaine, amphetamine, and methamphetamine and how this information may guide pharmacotherapy. <i>Methods</i>: We performed a cross-referenced literature search on pharmacogenetics, cocaine, amphetamine, and methamphetamine. <i>Results</i>: We describe functional genetic variants for enzymes dopamine-beta-hydroxylase (D&b.beta;H), catechol-<i>O</i>-methyltransferase (COMT), and dopamine transporter (DAT1), dopamine D4 receptor, and brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP; C-1021T) in the D&b.beta;H gene is relevant to paranoia associated with disulfiram pharmacotherapy for cocaine addiction. Individuals with variable number tandem repeats (VNTR) of the <i>SLC6A3</i> gene 3&prime;-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. <i>Conclusions</i>: Disulfiram and methylphenidate pharmacotherapies for cocaine addiction are optimized by considering polymorphisms affecting D&b.beta;H and DAT1 respectively. Altered subjective effects for amphetamine in DAT1 VNTR variants suggest a ‘protected’ phenotype. <i>Scientific Significance</i>: Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment. IS - 3 JF - The American Journal of Drug and Alcohol Abuse EP - 177 TI - Pharmacogenetic Treatments for Drug Addiction: Cocaine, Amphetamine and Methamphetamine PB - Informa Healthcare VL - 35 SP - 161 KW - addiction KW - cocaine KW - methamphetamine KW - pharmacogenetics AU - Haile, Colin AU - Kosten, Thomas AU - Kosten, Therese PY - 2009/// UR - http://dx.doi.org/10.1080/00952990902825447 ER -