Polymorphisms of the DRD2 , ANKK1 , DAT1 , DBH , and DRD4 genes have been found to moderate the effects of pharmacotherapy  of alcohol , opioid , and cocaine use disorders .
The integration of genetic information with clinical data will inform health professionals of the most efficacious pharmacotherapeutic intervention for substance use disorders .
Substance use disorders have significant personal , familial , and societal consequences .
Despite the serious consequences of substance use , only a few therapies are effective in treating substance use disorders , thus highlighting a need for improved treatment practice s. Substance use treatment response depends on multiple factors such as genetic , biological , and social factors .
It is essential that each component is represented in treatment plans .
The dopaminergic system plays a critical role in the pharmacotherapy for addictions , and an underst and ing of the role of variation of genes involved in this system is essential for its success .
The Mu-Opioid Receptor Gene Polymorphism (A118G) Alters HPA Axis Activation Induced by Opioid Receptor Blockade
An A118 G nucleotide exchange in exon 1 of the mu-opioid receptor causes an Asn40Asp substitution polymorphism in the receptor 's extracellular domain . In vitro studies show that the Asp40 variant of the mu-opioid receptor binds β-endorphin three times more avidly than the more common Asn40 variant . Paraventricular corticotropin releasing hormone neurons , which activate the HPA axis , express mu-opioid receptors and are modulated by β-endorphin neurons . This preliminary study was design ed to test the hypothesis that the Asn40Asp substitution polymorphism in the mu-opioid receptor influences HPA axis activation induced by opioid receptor blockade . Thirty-nine healthy men were genotyped ( A vs. G ) and then underwent opioid receptor blockade with Naloxone . Subjects expressing the A118 G receptor variant had greater cortisol responses to opioid receptor blockade . Also , a significant difference in the rate of increase of ACTH ( slope ) between A/A and A/G was observed between 30–90 minutes as well as a significant difference in the rate of decrease after 90 minutes . Moreover , subjects expressing the variant polymorphism had lower scores on the Conscientiousness Factor and associated subscales of NEO Personality Inventory compared to subjects expressing the common receptor . Because serotonin also modulates the CRF neuron , subjects were genotyped for a functional polymorphism within the serotonin transporter gene . We did not see differences in hormone responses result ing from expression of this functional polymorphism . It is plausible that persons expressing the mu-opioid receptor variant have altered HPA axis dynamics and altered responses to other physiological processes regulated through activation of the mu-opioid receptor
Polymorphisms of the DRD2 , ANKK1 , DAT1 , DBH , and DRD4 genes have been found to moderate the effects of pharmacotherapy  of alcohol , opioid , and cocaine use disorders .
The integration of genetic information with clinical data will inform health professionals of the most efficacious pharmacotherapeutic intervention for substance use disorders .
Substance use disorders have significant personal , familial , and societal consequences .
Despite the serious consequences of substance use , only a few therapies are effective in treating substance use disorders , thus highlighting a need for improved treatment practice s. Substance use treatment response depends on multiple factors such as genetic , biological , and social factors .
It is essential that each component is represented in treatment plans .
The dopaminergic system plays a critical role in the pharmacotherapy for addictions , and an underst and ing of the role of variation of genes involved in this system is essential for its success .