Pharmacogenetic Treatments for Alcohol and Stimulants

Pharmacogenetics uses genetic tests to predict the effectiveness of medication treatments for individual patients with drug dependence such as alcohol and opiates. An important shared neurobiological component of the reinforcement and dependence on alcohol and opiates is alcohol's enhancement of β-endorphin release. The physiological and subjective effects of both alcohol and opiates are associated with β-endorphin and the mu opiate system. A pharmacotherapy that has been effective for both disorders is naltrexone, which increases baseline β-endorphin release blocking further release by alcohol. Naltrexone's action as an alcohol pharmacotherapy is facilitated by a putative functional single nucleotide polymorphism (SNP) in the opioid mu receptor gene (Al18G) which alters its receptor function. Patients with this SNP have significantly lower relapse rates to alcoholism when treated with naltrexone. This SNP is particularly common among northern Chinese suggesting an important role for naltrexone treatment of alcoholism in China. Another important genetic polymorphism related to stimulant and perhaps other types of dependence frequently occurs (about 40% of the population) in the promoter region of the gene coding for dopamine beta hydroxylase (DβH). This polymorphism leads to 10 to 100 times lower levels of the DβH enzyme, which converts dopamine to norepinephrine in neurons. Stimulant abusers with normal levels of this enzyme show significant reductions in stimulant abuse when treated with DβH inhibitors, while those with the polymorphism for low DβH levels show no treatment efficacy with these medications. Pharmacogenetics has great potential for improving treatment outcome as we identify gene variants that affect pharmacodynamic as well as the more commonly studied pharmacokinetic factors. These mutations can guide pharmacotherapeutic agent choice for optimum treatment of alcohol and stimulant abuse and reduce relapse after successful initial abstinence.