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Updated: Jun 23, 2026

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine
Colin N Haile1, Thomas R Kosten, Therese A Kosten
1Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, and Michael E DeBakey VA Medical Center, Houston, Texas 77030, USA.
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.
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