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Cannabinoids Show Promise In Slowing MS, But ‘High’ Raises Concern
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Study after study suggests cannabinoids could be the key to slowing multiple sclerosis, but researchers are finding it hard to develop a treatment that doesn’t get patients high.

Cannabinoids are a class of chemicals found in marijuana. They’re also the main ingredients in cannabis-based treatments for multiple sclerosis (MS), such as Sativex.

But so far, cannabinoids are only recognized for their ability to manage symptoms of the disorder, according to U.S. researcher Yumin Zhang, MD, Ph.D, who also points to their psychoactive effects as a major drawback.

The THC compound is certainly already being used in Canada and several European countries. They have some effects in pain and spasticity. But for these exogenous cannabinoids, there is always concern about the side effect.

As a result, scientists like Dr. Zhang have begun to investigate a variety of synthetic cannabinoids – hoping to mimic the protective effects of marijuana-derived compounds while reducing their psychoactivity.

But studies continue to suggest that this may be a difficult goal to achieve.

Published online in the journal Neuroscience, Dr. Zhang and colleagues from the Uniformed Services University of the Health Sciences decided to further clarify the different roles of cannabinoid pathways in a mouse model of MS.

While CB1 receptors are responsible for the high associated with marijuana, CB2 receptors have no psychoactive effect and are thus the primary focus of new cannabinoid therapies.

But like many before, the study concluded that it was CB1 activity, not CB2, that “contributes significantly to the anti-inflammatory and neuroprotective effects of cannabinoids in MS.”

Indeed, the potential for cannabinoids to protect neurons from MS-related damage has inspired hope for treatments that can cure, or at least slow, the degenerative disorder.

[pullquote align=”right”]”I think any drug, if used at a certain high dose, always has a side effect”[/pullquote]

Dr. Zhang says some synthetics like CB52 – one of the cannabinoids used in the latest study – have shown promising results in early stage research. However, it is difficult to distinguish its therapeutic effect from its potential side effects, because CB52 acts on both CB1 and CB2 receptors.

Using this compound, we found that in in vitro studies, certainly they have a better effect compared to other compounds. That’s one of the reasons why we use this. But I still don’t know the potential for this particular drug to be used in clinical studies. I think any drug, if used at a certain high dose, always has a side effect.

After conducting a number of studies involving cannabinoids and MS models, Dr. Zhang concedes that it may be more ideal to target both CB1 and CB2 receptors instead of only CB2.

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But he hopes that new drugs can improve on the effectiveness of traditional cannabinoids.

“I still think that maybe both CB1 and CB2 receptor activation should be more ideal,” Dr. Zhang says.

“The important thing is how to really enhance the protective effect and at the same time reduce the side effects. Augmentation of the endogenous levels of cannabinoids might be an alternative and a better approach for the treatment of MS, and possibly other neurological diseases.”

The study was published ahead of print and received funding from the National Multiple Sclerosis Society, the Defense Medical Research and Development Program and the Uniformed Services University

(Revised on 10/09/13)

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