This study will elucidate the pharmacogenetic effects of the Asn40Asp SNP of the OPRM1 gene on biobehavioral and neural markers of response to naltrexone in individuals of East Asian descent, an ethnic group most likely to express the positive predictive allele.
Name: Naltrexone
Description: Naltrexone is an opioid receptor antagonist with highest affinity for mu opioid receptorsType: DrugNaltrexone
Name: Placebo
Description: Sugar pill, matched to the active study medication in capsule size and colorType: DrugSugar pill
Description: Biphasic Alcohol Effects Scale (BAES) Alcohol Urge Questionnaire (AUQ)
Measure: Subjective Effects of Alcohol Time: During the alcohol administration and observation period which is expected to last a total of 4 hoursDescription: Alcohol taste cues task for fMRI
Measure: Neural response to alcohol cues Time: During the alcohol cue exposure fMRI paradigm which is expected to last 45 minutesDescription: Time to first drink and total number of drinks are the primary outcome variables for the alcohol self-administration task
Measure: Alcohol self-administration Time: Alcohol self-administration period will last 2 hoursAllocation: Randomized
Crossover Assignment
There are 2 SNPs
Inclusion Criteria: - current (i.e., past month) alcohol dependence - East Asian ethnicity (i.e., Chinese, Korean, or Japanese) - Prospective genotyping for the A118G SNP of the mu opioid receptor (OPRM1) gene to allow for balanced groups on all three genotypes (AA, AG, GG) Exclusion Criteria: - lifetime DSM-IV of drug dependence (other than alcohol or nicotine) - current use of psychoactive drugs as determined by self-reports and verified using toxicology testing - lifetime diagnosis of bipolar disorder or any psychotic disorder - contraindications to an MRI scan (including left handedness) Inclusion Criteria: - current (i.e., past month) alcohol dependence - East Asian ethnicity (i.e., Chinese, Korean, or Japanese) - Prospective genotyping for the A118G SNP of the mu opioid receptor (OPRM1) gene to allow for balanced groups on all three genotypes (AA, AG, GG) Exclusion Criteria: - lifetime DSM-IV of drug dependence (other than alcohol or nicotine) - current use of psychoactive drugs as determined by self-reports and verified using toxicology testing - lifetime diagnosis of bipolar disorder or any psychotic disorder - contraindications to an MRI scan (including left handedness) Alcohol Use Disorder Alcohol Drinking Alcoholism Recent pharmacogenetic studies have advanced the gene coding for µ-opioid receptors (OPRM1) gene as a potential moderator of responses to naltrexone. --- A118G ---
Inclusion Criteria: - current (i.e., past month) alcohol dependence - East Asian ethnicity (i.e., Chinese, Korean, or Japanese) - Prospective genotyping for the A118G SNP of the mu opioid receptor (OPRM1) gene to allow for balanced groups on all three genotypes (AA, AG, GG) Exclusion Criteria: - lifetime DSM-IV of drug dependence (other than alcohol or nicotine) - current use of psychoactive drugs as determined by self-reports and verified using toxicology testing - lifetime diagnosis of bipolar disorder or any psychotic disorder - contraindications to an MRI scan (including left handedness) Inclusion Criteria: - current (i.e., past month) alcohol dependence - East Asian ethnicity (i.e., Chinese, Korean, or Japanese) - Prospective genotyping for the A118G SNP of the mu opioid receptor (OPRM1) gene to allow for balanced groups on all three genotypes (AA, AG, GG) Exclusion Criteria: - lifetime DSM-IV of drug dependence (other than alcohol or nicotine) - current use of psychoactive drugs as determined by self-reports and verified using toxicology testing - lifetime diagnosis of bipolar disorder or any psychotic disorder - contraindications to an MRI scan (including left handedness) Alcohol Use Disorder Alcohol Drinking Alcoholism Recent pharmacogenetic studies have advanced the gene coding for µ-opioid receptors (OPRM1) gene as a potential moderator of responses to naltrexone. --- A118G --- --- A118G ---
Naltrexone for Individuals of East Asian Descent This study will elucidate the pharmacogenetic effects of the Asn40Asp SNP of the OPRM1 gene on biobehavioral and neural markers of response to naltrexone in individuals of East Asian descent, an ethnic group most likely to express the positive predictive allele. --- Asn40Asp ---
The most widely studied polymorphism of the OPRM1 gene is the Asn40Asp single nucleotide polymorphism (SNP), a functional mutation thought to affect receptor activity such that the Asp40 variant binds β-endorphin three times stronger than the Asn40 allele. --- Asn40Asp ---
This pilot study also found support for a gene dose-response, such that Asp40Asp individuals showed greater NTX responsivity than those with the Asn40Asp genotype. --- Asn40Asp ---
This study seeks to build upon these preliminary findings by testing heavy drinkers of East Asian descent across three OPRM1 genotypes (Asn40Asn, n = 30; Asn40Asp, n = 30, and Asp40Asp, n = 30). --- Asn40Asp ---
This study will elucidate the pharmacogenetic effects of the Asn40Asp SNP of the OPRM1 gene on biobehavioral and neural markers of response to naltrexone in individuals of Asian descent, an ethnic group most likely to express the positive predictive allele (Asp40). --- Asn40Asp ---