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
Name: Placebo
Description: Alcohol Urge Questionnaire (AUQ) is used to assess subjective experiences of craving for alcohol. It consists of 8 items, each rated on a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). A summary score is used at each assessment time point. The AUQ was administered at baseline and three levels of breath alcohol concentration: 0.02 g/dl. 0.04, g/dl, and 0.06 g/dl.
Measure: Subjective Response - Craving for Alcohol Time: The AUQ was administered across a period of approximately 1.5 hours.Description: The Biphasic Alcohol Effects Scale (BAES) Stimulant Subscale consists of 14 items designed to capture the stimulant effects of alcohol, rated on an 11-point scale (0 = not at all. 10 = extremely). Total score for the stimulant subscale ranges from 0-70.
Measure: Subjective Response - Stimulation Time: The BAES Stimulant Subscale was administered at baseline and three levels of breath alcohol concentration: 0.2 g/dl. 0.04, g/dl, and 0.06 g/dl taking place within approximately 1.5 hoursDescription: The Biphasic Alcohol Effects Scale (BAES) Sedation Subscale consists of 14 items designed to capture the sedating effects of alcohol, rated on an 11-point scale (0 = not at all. 10 = extremely). Total score for the sedation subscale ranges from 0-70.
Measure: Subjective Response - Sedation Time: The BAES Sedation Subscale was administered at baseline and three levels of breath alcohol concentration: 0.2 g/dl. 0.04, g/dl, and 0.06 g/dl taking place within approximately 1.5 hoursDescription: Alcohol taste cues task for functional magnetic resonance imaging (fMRI). Region of Interest (ROI) were atomically defined using the Harvard-Oxford atlas in standard Montreal Neurological Institute (MNI) space, which were transformed into individual participants' native space using Functional Magnetic Resonance Imaging of the Brain Software Library (FSL). Contrast estimates are for Alc > Water cue, and are arbitrary units.
Measure: Neural Response to Alcohol Cues Time: During the alcohol cue exposure fMRI paradigm which is expected to last 45 minutesDescription: Total number of drinks consumed during the alcohol self-administration task
Measure: Alcohol Self-administration - Number of Drinks Time: Alcohol self-administration period was 1 hour longAllocation: 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 Alcoholism Alcohol Drinking 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 Alcoholism Alcohol Drinking 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 ---