A large clinical trial from the UK has found tetrahydrocannabinol (THC), an active ingredient of marijuana, doesn't prevent the progression of multiple sclerosis (MS). The study was published today in Lancet Neuology, while the findings were first announced at a medical conference last year.

The findings comes from the CUPID (Cannabinoid Use in Progressive Inflammatory Brain Disease) study, an investigation from the University of Plymouth that involved from the 500 patients with progressive MS, a subtype of MS characterized by a progressive worsening of the condition. Plymouth's study is the largest to date on the use of the cannabinoid THC with MS.

Multiple sclerosis, an autoimmune disease that is the most common cause of neurological disability in young adults, typically begins in one of two ways. Those with relapsing-remitting MS — 80 percent of initial cases — experience intermittent attacks of severe symptoms, which can include impaired vision, severe fatigue, muscle spasms, or balance disruption.

A second possible diagnosis during the early stages is primary-progressive MS, which features these symptoms from the outset and is marked by the gradual worsening of the disease.

Over 50 percent of relapsing patients eventually develop the progressive form, typically within 10 years. This means the overwhelming bulk of MS cases are classified progressive at some point, but there are currently no drugs to treat this stage of the condition.

"Current treatments for MS are limited, either being targeted at the immune system in the early stages of the disease or aimed at easing specific symptoms such as muscle spasms, fatigue, or bladder problems," said lead author Dr. John Zajicek, a clinical neuroscientist at Plymouth University Peninsula Schools of Medicine and Dentistry. "At present there is no treatment available to slow MS when it becomes progressive."

After initial results from Plymouth's CUPID program in 2003 suggested THC could slow disability in progressive MS over the course of a year, the researchers embarked on an extended 3-year follow-up. But results from this trial have been less promising.

"Overall our research has not supported laboratory based findings and shown that, although there is a suggestion of benefit to those at the lower end of the disability scale when they joined CUPID, there is little evidence to suggest that THC has a long term impact on the slowing of progressive MS," said Zajicek.

Is This The End Of The Line For Medical Marijuana Use With Multiple Sclerosis Patients?


It is possible that the dosage was too low, at least that is suggestion posed by neurologists Dr. Olaf Stuve of University of Texas, Southwestern and Dr. Friedemann Paul of Charité-Universitätsmedizin Berlin.

"Although the results of this trial suggest that the tested dose is safe, the drug might have been used at a suboptimal dose, or introduced at a disease stage when neurological degeneration could no longer be changed," write Stuve and Paul in an accompanying Lancet Neurology commentary.

In addition there is currently no method for directly measuring inflammation within the brain of an MS patient, meaning the CUPID study had to rely on a readout of general symptoms. Given the target of THC is inflammation, it is possible that a potential benefit went undetected. This inconclusiveness highlights the paramount need for better diagnostics for MS.

It's worth investigating whether combined punch of the compounds, are required for a measurable effect. Similarly, smoking marijuana may have differential effects relative to taking a THC pill, as it is possible that other cannabinoids, which could be another avenue of future research.

For now this CUPID trial falls into the collection of mixed results seen with prior research on medical marijuana use with MS, but it does highlight one important reminder about science: even a negative result can tell you something.

Source: Zajicek J, Ball S, Wright D et al. Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a randomised, placebo-controlled trial. Lancet Neurology. 2013.

Stuve O, Paul F. Progressive multiple sclerosis: desperately seeking remedy. Lancet Neurology. 2013.