30 patients diagnosed with medication overuse headache were randomly assigned to receive either nabilone or ibuprofen for each treatment period. This cross-over study consisted of two 8-week treatment periods, each with 1 week of washout before, and a 2-week discontinuation period at the end of the study. Patients were assessed for the reduction in headache frequency, pain intensity, duration, daily analgesic intake, the incidence of adverse events, and quality of life. Results demonstrated that nabilone significantly reduced daily analgesic intake, headache pain and duration, and quality of life after each 8-week treatment period, while no serious adverse events were reported.