Tetrahydrocannabinol, the main active ingredient in marijuana, did not slow the progression of multiple sclerosis in a 3-year, randomized trial of 493 British patients with primary or secondary progressive forms of the disease.

Some patients with lower baseline EDSS (Expanded Disability Status Scale) scores appeared to have delayed progression, but the trial did not have enough statistical power to allow comparison of subgroups.

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A trial with “disappointing” results indicated that the main ingredient in marijuana did not slow the progression of multiple sclerosis.
In the Cannabinoid Use in Progressive Inflammatory Brain Disease (CUPID) trial, investigators randomized 329 patients to 14-28 mg of tetrahydrocannabinol (THC)/day in capsule form based on weight, and 164 to placebo. Their mean baseline EDSS score was about 5.8 (range, 4.0-6.5). Patients were, on average, 52 years old; and about 60% were women.

None were on disease-modifying therapies, but most were on pain relievers and other medications for symptom relief. The patients agreed to otherwise abstain from marijuana during the study.

Compared with placebo, the hazard ratio for EDSS progression in the THC group – defined as a 1-point increase for patients starting at or below 5, and a half-point increase for those starting above – was 0.92 (95% CI, 0.68-1.23) after adjustment for disease type, age, and other variables.

There were no statistical differences in brain volume loss on MRI, Multiple Sclerosis Impact Scale scores, and several secondary outcomes, including the 25-foot timed walk and 9-hole peg tests.

On post hoc analysis, there was a hint of delayed progression in patients with baseline EDSS scores below 6; 26 (76%) of 34 placebo patients in that group progressed, compared with only 44 (58%) of 76 in the THC group.

“The lower EDSS scores do seem to suggest a treatment effect, but we did not have much power to detect that effect. I do think that there are probably going to be subgroups that do respond more than others,” said lead investigator Dr. John Zajicek, a professor of clinical neuroscience at Plymouth (England) University.

Dr. John Zajicek
Overall, he called the results “disappointing.” Although “there is sufficient evidence to use cannabinoids” for relieving muscle stiffness, spasticity, pain, urinary disturbances, and other MS symptoms, it could be that THC simply does not slow progression in primary or secondary progressive MS. No drug has yet been proven to do so, Dr. Zajicek said at the Fourth Cooperative Meeting on Multiple Sclerosis.

The results might also have been obscured because there was very little progression in either the THC or placebo groups. “We were expecting 70% progression, but we got just over 40%, so most of the outcome measures did not change very much over 3 years. It’s very difficult to find a treatment effect when your outcome measures aren’t changing,” he said.

About 60% of the THC patients complained of dizziness or lightheadedness, and 51% of thought or perception changes, both far more common than in the placebo group, but fewer THC patients reported musculoskeletal pain (26% vs. 37% in the placebo group) and fewer developed urinary tract infections (26% vs. 35%).

The meeting was sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis. Dr. Zajicek said he had no relevant disclosures.