Cannabinoids reduce allodynia/hyperalgesia in animal pain models, but few clinical studies evaluated the analgesic action in humans. We aimed to evaluate the effect of delta-9-tetrahydrocannabinol (dronabinol) on central pain in MS patients. Twenty-four MS patients participated in a double-blind placebo-controlled crossover trial. Dronabinol reduced the spontaneous pain intensity significantly compared with placebo (4.0 (2.3-6.0) vs. 5.0 (4.0-6.4), median (25th-75th percentiles), p = 0.02). Though dronabinol's analgesic effect is modest, its use should be evaluated considering the general difficulty in treating central pain.