Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial

Abstract

Objective: To evaluate the effect of the oral synthetic delta-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis.

Design: Randomised double blind placebo controlled crossover trial.

Setting: Outpatient clinic, University Hospital of Aarhus, Denmark.

Participants: 24 patients aged between 23 and 55 years with multiple sclerosis and central pain.

Intervention: Orally administered dronabinol at a maximum dose of 10 mg daily or corresponding placebo for three weeks (15-21 days), separated by a three week washout period.

Main outcome measure: Median spontaneous pain intensity (numerical rating scale) in the last week of treatment.

Results: Median spontaneous pain intensity was significantly lower during dronabinol treatment than during placebo treatment (4.0 (25th to 75th centiles 2.3 to 6.0) v 5.0 (4.0 to 6.4), P = 0.02), and median pain relief score (numerical rating scale) was higher (3.0 (0 to 6.7) v> 0 (0 to 2.3), P = 0.035). The number needed to treat for 50% pain relief was 3.5 (95% confidence interval 1.9 to 24.8). 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.

Conclusions: Dronabinol has a modest but clinically relevant analgesic effect on central pain in patients with multiple sclerosis. Adverse events, including dizziness, were more frequent with dronabinol than with placebo during the first week of treatment.

Fig 1

Flow diagram of patients enrolled in study. ECG=electrocardiogram

Fig 2

Spontaneous pain intensity during one week baseline, last week of active treatment, and last week of placebo treatment. Each line represents one patient. Active-placebo group=patients randomised to active medication in first treatment period (n=12); placebo-active group=patients randomised to placebo in first treatment period (n=12); NRS=numerical rating scale