The effects of nabilone on sleep in fibromyalgia: Results of a randomized controlled trial

Objective: Fibromyalgia (FM) is a chronic pain syndrome associated with dysregulation of central nervous system pain processing. Insomnia affects over 75% of patients, and tricyclic antidepressants are the mainstay of treatment. Cannabis is used by some patients with FM to help sleep. We evaluated the safety and efficacy of nabilone, a synthetic cannabinoid, on sleep disturbance in FM. Methods: We conducted a randomized double-blind active control equivalency crossover trial to compare nabilone (0.5-1.0mg before bedtime) to amitriptyline (10-20mg before bedtime) in FM patients with chronic insomnia. Subjects received each drug for two weeks with a two-week washout period. The primary outcome was sleep quality, measured by the Insomnia Severity Index (ISI) and the Leeds Sleep Evaluation Questionnaire (LSEQ). Secondary outcomes included pain, mood, quality of life and adverse events (AEs). Results: Thirty-one subjects were enrolled and 29 completed the trial (26 female, mean age 49.5 years). While sleep was improved by both amitriptyline and nabilone, nabilone was superior to amitriptyline (ISI difference=3.2, 95% CI 1.2-5.3). Nabilone was marginally better on the restfulness (LSEQ difference=0.5 (0.0-1.0) but not on wakefulness (difference=0.3 (-0.2, 0.8)). Adverse events (AEs) were mostly mild to moderate and were more frequent with nabilone. Most common AEs for nabilone were dizziness, nausea and dry mouth. Conclusion: Nabilone is effective in improving sleep in patients with FM and is well tolerated. Low dose nabilone given once daily at bedtime may be considered as an alternative to amitriptyline. Longer trials are needed to determine the duration of effect and to characterize long-term safety. The trial was conducted following Good Clinical Practice guidelines and was registered at www.clinicaltrials.gov (registration number NCT00381199).