Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine

Am J Drug Alcohol Abuse. 2009;35(3):161-77. doi: 10.1080/00952990902825447.


Background: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amphetamine / adverse effects
  • Amphetamine-Related Disorders / drug therapy*
  • Amphetamine-Related Disorders / genetics
  • Cocaine-Related Disorders / drug therapy*
  • Cocaine-Related Disorders / genetics
  • Disulfiram / adverse effects
  • Disulfiram / therapeutic use
  • Dopamine Uptake Inhibitors / therapeutic use
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Methamphetamine / adverse effects
  • Methylphenidate / therapeutic use
  • Pharmacogenetics / methods*
  • Polymorphism, Single Nucleotide


  • Dopamine Uptake Inhibitors
  • Enzyme Inhibitors
  • Methylphenidate
  • Methamphetamine
  • Amphetamine
  • Disulfiram