The effect of beforehand and simultaneous oral contraceptive administration on urine total and free morphine concentration in tolerance and dependency models of rat

Addiction to opioid drugs is considered as a problem throughout the world. Addiction can be studied concerning: social, medical and psychological aspects. The social aspect of addiction is quite important. For example, the negative result of addiction test is a requirement for marriage and job by law. On the other hand, frauds in addiction tests have been reported (such as displacement of urine from bladder, alkalization or acidification of urine and taking of diuretics or oral contraceptives). In the present study, two different chronic morphine administration protocols (tolerance and dependency models) were applied. Estrogen and progesterone were given prior and simultaneously with morphine. After the last injection of morphine, urine samples were taken every 6 h for 24 h. Then morphine was quantitatively detected by High Performance Liquid Chromatography (HPLC). Data analysis was performed using two-way ANOVA and repeated measures ANOVA test followed by Student-Newman-Keuls test. Conjugated morphine was measured by the subtraction of free part of morphine from the total one in the urine samples. Our results indicated that prior administration of estrogen and progesterone increased the metabolism of morphine 6 and 12 h after the last injection, while no significant change was detected after 18 and 24 h. In summary, it can be concluded that estrogen and progesterone transiently affect the metabolism of morphine. Thus, the effect of the sex hormones on morphine metabolism is not clinically important.