THC and Cannabis Extract Did Not Reduce Spasticity in This MS Trial | Research

The takeaway

A randomized trial in 16 MS patients found that neither oral THC nor cannabis plant extract reduced spasticity compared to placebo, and both treatments worsened patients' overall impression of their condition.

Read this if you have MS and are considering cannabis for spasticity and want to see the full picture of clinical evidence.

Neither THC nor plant extract reduced spasticity; both worsened global impression

What the researchers found

In this randomized, double-blind, placebo-controlled crossover study, 16 patients with severe multiple sclerosis spasticity received oral THC, cannabis plant extract, and placebo in different periods. Both active treatments were considered safe, but adverse events were more common with plant extract.

Neither THC nor plant extract reduced spasticity compared to placebo. Perhaps most notably, both active treatments worsened patients' global impression of their condition, suggesting that any potential benefits were outweighed by side effects experienced during the treatment periods.

Why it matters

This study stood out because it found no benefit, directly contradicting the narrative from some other trials and patient reports suggesting cannabinoids help MS spasticity. The finding that patients actually felt worse overall on cannabinoid treatment highlighted the importance of controlled trials over anecdotal reports and raised questions about publication bias in cannabinoid research.

The numbers in context

Sixteen patients with severe MS spasticity were enrolled. The study used a twofold crossover design testing THC and plant extract against placebo.

How the study worked

This was a randomized, double-blind, placebo-controlled, twofold crossover study. Sixteen patients with MS and severe spasticity received oral THC, cannabis sativa plant extract, and placebo in a crossover design. Spasticity was measured using standardized assessments, and patients rated their global impression of change.

What this study cannot tell us

The sample of 16 patients was small and may have been underpowered to detect modest benefits. Only patients with severe spasticity were included, which may represent a population less responsive to cannabinoid treatment. The specific doses and titration schedule were not detailed in the abstract.

How to read the evidence

This is a randomized, double-blind, placebo-controlled crossover trial, though limited by its small sample of 16 patients.

When this study was published

Published in 2002. Larger subsequent trials found more favorable results, and Sativex was later approved for MS spasticity in several countries.

The bigger picture

This negative result was published around the same time as larger trials (particularly the CAMS study) that found more positive results for cannabinoids in MS. The contrast illustrates how small trials can produce different results than larger ones. Sativex (nabiximols) was subsequently approved in several countries for MS spasticity, suggesting that formulation, dosing, and patient selection may explain divergent trial results.

Questions still open

Why did this trial produce negative results when other MS-cannabinoid trials found benefits? Did the severity of spasticity in this patient population influence the outcome? Would different dosing or different cannabinoid formulations have produced different results?

Common questions

Does cannabis help with MS spasticity?

This small trial found no benefit, but larger trials conducted around the same time found positive results. Sativex (a cannabis-based mouth spray) was subsequently approved for MS spasticity in several countries, suggesting that the overall evidence supports some benefit, though individual responses vary.

Why might this trial have gotten different results than larger trials?

Small trials are more susceptible to chance variation. Additionally, this trial enrolled only patients with severe spasticity, used specific oral formulations, and may have used different dosing schedules than trials that found benefits.

Read the original research

Safety, tolerability, and efficacy of orally administered cannabinoids in MS.

Neurology, 58(9), 1404-7

View on PubMed ↗

Citation

Killestein, J; Hoogervorst, E L J; Reif, M; Kalkers, N F; Van Loenen, A C; Staats, P G M; Gorter, R W; Uitdehaag, B M J; Polman, C H. (2002). Safety, tolerability, and efficacy of orally administered cannabinoids in MS.. Neurology, 58(9), 1404-7.