Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine.
BACKGROUND
Pharmacogenetics uses genetic variation to predict individual differences in response to medications and holds much promise to improve treatment of addictive disorders.


OBJECTIVE
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.


CONCLUSIONS
Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment.
Haile
Colin N
CN
Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, and Michael E DeBakey VA Medical Center, Houston, Texas 77030, USA.
Kosten
Thomas R
TR
Kosten
Therese A
TA
D000661:Amphetamine / Q000009:adverse effects; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000235:genetics; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000235:genetics; D004221:Disulfiram / Q000009:adverse effects / Q000627:therapeutic use; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008694:Methamphetamine / Q000009:adverse effects; D008774:Methylphenidate / Q000627:therapeutic use; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide
D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D008774:Methylphenidate; D008694:Methamphetamine; D000661:Amphetamine; D004221:Disulfiram