The objective of this crossover RCT was to evaluate the effect of the oral synthetic delta-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis. Twenty-four patients aged between 23 and 55 years with multiple sclerosis and central pain were included. Oral dronabinol was given at a maximum dose of 10 mg daily or corresponding placebo for 3 weeks (15–21 days), separated by a 3-week washout period. Median spontaneous pain intensity was significantly lower during dronabinol treatment than during placebo treatment and median pain relief score. The NNT for 50% pain relief was 3.5. On the SF-36 quality of life scale, the two items bodily pain and mental health indicated benefits from active treatment compared with placebo. The number of patients with adverse events was higher during active treatment, especially in the first week of treatment. The functional ability of the multiple sclerosis patients did not change.