Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial

Background:

Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom.

Methods:

We conducted a placebo-controlled, crossover trial involving adult patients with multiple sclerosis and spasticity. We recruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three days) or control (identical placebo cigarettes, once daily for three days). Each participant was assessed daily before and after treatment. After a washout interval of 11 days, participants crossed over to the opposite group. Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale. Our secondary outcomes included patients’ perception of pain (as measured using a visual analogue scale), a timed walk and changes in cognitive function (as measured by patient performance on the Paced Auditory Serial Addition Test), in addition to ratings of fatigue.

Results:

Thirty-seven participants were randomized at the start of the study, 30 of whom completed the trial. Treatment with smoked cannabis resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo (p = 0.008). Scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). No serious adverse events occurred during the trial.

Interpretation:

Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.Spasticity is a common and disabling symptom that remains a substantial problem for many patients with multiple sclerosis. Some patients have adverse effects from conventional antispasticity medications; for others, spasticity persists despite treatment. A report from the Institute of Medicine in the United States concluded that the active compounds of cannabis (marijuana) are potentially effective in treating neurologic conditions and “should be tested rigorously in clinical trials.”¹ There is evidence that the cannabinoid receptors CB₁ and CB₂ may be involved in the control of spasticity in multiple sclerosis² and that the endogenous ligand of CB₁, anandamide, is itself an effective antispasticity agent.³ CB₁ receptors are primarily presynaptic; their activation inhibits calcium influx and glutamate release, and reduces neuronal excitability by activating somatic and dendritic potassium channels.⁴Although many patients with multiple sclerosis endorse smoking cannabis as therapy, evidence that it relieves spasticity is largely anecdotal, as most trials focus on orally administered cannabinoids. We sought to assess the safety and efficacy of smoked cannabis versus placebo in patients with multiple sclerosis who have treatment-resistant spasticity.