Abstract
G-carriers of the functional SNP A118G of the μ-opioid receptor gene OPRM1 have been associated with decreased pain sensitivity in men, and in alcoholic G-carriers a greater effect of naltrexone treatment has been found. This study investigated differences in subjective effects of μ-opioid manipulation between A homozygotes and G carriers in a group of healthy males. We hypothesised that G-carriers would show higher sensitivity to naltrexone and lower sensitivity to morphine. In a randomized double blind cross-over study, 49 healthy males received morphine (10 mg), naltrexone (50 mg) or placebo per-orally on three separate days. They completed a 21 variable questionnaire on four different time intervals (0 min, 60 min, 120 min, 150 min). Based on a principal component analysis, the variables were sorted into four components: Lethargy , Wellbeing , Discomfort and Other . The data were based on a principal component analysis scores, and run through a separate 3x3 repeated measure ANOVA for all the components. Significant main effects of drug and time in the components Lethargy and Other were observed. For Lethargy , both naltrexone and morphine gave increased ratings compared to placebo, but the increase was only significant for naltrexone. No significant main effects of genotype or interaction effects between drug and genotype was observed in any of the four components. This might be due the low doses of morphine, but may also be an indication of differences in the effect of drug when the system is disturbed, like during pain or addiction.
G-carriers of the functional SNP A118G of the μ-opioid receptor gene OPRM1 have been associated with decreased pain sensitivity in men, and in alcoholic G-carriers a greater effect of naltrexone treatment has been found. This study investigated differences in subjective effects of μ-opioid manipulation between A homozygotes and G carriers in a group of healthy males. We hypothesised that G-carriers would show higher sensitivity to naltrexone and lower sensitivity to morphine. In a randomized double blind cross-over study, 49 healthy males received morphine (10 mg), naltrexone (50 mg) or placebo per-orally on three separate days. They completed a 21 variable questionnaire on four different time intervals (0 min, 60 min, 120 min, 150 min). Based on a principal component analysis, the variables were sorted into four components: Lethargy , Wellbeing , Discomfort and Other . The data were based on a principal component analysis scores, and run through a separate 3x3 repeated measure ANOVA for all the components. Significant main effects of drug and time in the components Lethargy and Other were observed. For Lethargy , both naltrexone and morphine gave increased ratings compared to placebo, but the increase was only significant for naltrexone. No significant main effects of genotype or interaction effects between drug and genotype was observed in any of the four components. This might be due the low doses of morphine, but may also be an indication of differences in the effect of drug when the system is disturbed, like during pain or addiction.