Taranabant, an orally active, potent, and highly selective CB-1 receptor inverse agonist, is being developed for the treatment of obesity. This randomized, placebo-controlled, multiple-dose, crossover study evaluated the effect of taranabant on the pharmacokinetics of ethinyl estradiol and norelgestromin in healthy women receiving > or =3 months of therapy with oral contraceptives. Nineteen participants with normal menstrual cycles received oral contraceptives on days 1 to 21 during 2 consecutive contraceptive cycles. Participants received taranabant 6 mg/day or placebo on days 1 to 21 of each contraceptive cycle. Plasma samples were collected predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose on day 21 of each cycle for determination of AUC0-24 h and Cmax of ethinyl estradiol and norelgestromin. Lack of a clinically important effect was declared if the 90% confidence intervals for the geometric mean ratio of AUC0-24 h and Cmax in the absence and presence of taranabant were contained within the predefined bounds of (0.8, 1.25). The geometric mean ratios and 90% confidence intervals of ethinyl estradiol and norelgestromin, respectively, were 0.93 (0.87, 1.00) and 1.02 (0.96, 1.09) for AUC0-24 h and 0.95 (0.88, 1.01) and 0.95 (0.88, 1.01) for Cmax. In summary, coadministration of multiple-dose taranabant 6 mg with oral contraceptives did not lead to clinically meaningful alterations in the pharmacokinetic profiles of ethinyl estradiol or norelgestromin.