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| MS in focus Issue
15
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2010
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Richard Hosking and John Zajicek, Clinical Neurology Research Group, Peninsula Medical School, Plymouth, UK |
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(Adam Ross/flickr)
The plant Cannabis sativa has attracted medicinal interest throughout history. Modern cannabis research stems from the 1960s, when Israeli scientist Raphael Mechoulam discovered the plant’s active molecules, which he called cannabinoids. This led to the discovery of the body’s own cannabinoid system, which is important in many organs including the brain.
People with MS report improved symptoms following cannabis use, and here we describe the scientific background, clinical trials, potential risks and legal issues involved.
Scientific background
Cannabis is known by a variety of names: for example marijuana describes dried leaves, while hashish refers to blocks of resin. The plant contains over 60 cannabinoids (CB) with different biological activity. Tetra-hydro-cannabinol (THC) is the main psychoactive cannabinoid, and synthetic CB have also been developed. So far, two specific CB receptors (CBR) have been discovered. Surprisingly, the first (CB1R) is the most common among all receptors within the nervous system.
The highest number of CB1R occur in brain regions involved with thinking, memory, movement and coordination. This explains why cannabis users experience difficulty in these areas. The second receptor (CB2R) is found on cells of the immune system. Animal experiments highlight the importance of CB in many disease processes relevant to MS. Significantly, studies of MS postmortem brain tissue show that many cell-types involved express CBR. Work is ongoing in trying to determine what their purpose may be.
Clinical trials
The hope that cannabis may help MS has led to numerous clinical trials. However, treatment response in MS is difficult to evaluate, and reliable studies require large numbers of subjects and careful planning. The psychoactivity of THC causes further complications. Nevertheless, results have been encouraging – particularly in relation to pain, muscle stiffness and bladder disturbance.
Pain is a significant feature of MS. Animal studies show that CBR are important in pain control. Several trials have confirmed that cannabis-based treatments alleviate MS-related neuropathic pain. Surveys of people with MS who smoke cannabis often report improved muscle stiffness (spasticity).
Animal studies show that CB1R activation is central to this. The Cannabinoids in Multiple Sclerosis study recruited more than 600 subjects for 15 weeks and confirmed improvements in selfreported spasticity and pain. A significant reduction in clinical spasticity occurred after 12 months of treatment.
Animal data also imply that immune-cell CB2R-activation produces anti-inflammatory effects which may slow disease progression. The follow-up study showed a relative preservation of walking ability, which will be further assessed. Finally, some results suggest that cannabis extract reduces bladder dysfunction via CB1R activation.
Cannabis preparations
It is not known which cannabinoids (plant-based or synthetic, alone or in combination) are most effective in MS. Importantly, plant-CB activity is altered by methods of drug preparation. For example, heating (that is, smoking) may destroy anti-inflammatory properties. Liver metabolism also reduces drug activity, but is bypassed with oral sprays which allow direct bloodstream absorption. A cannabis-based medicinal-extract (CBME) spray called Sativex®, which contains THC and cannabidiol, is licensed in Canada for MS-related neuropathic pain, and can be prescribed in the UK on a named-patient basis. Sativex® is currently undergoing further tests before receiving a full UK MS-licence. Another CBME, named Cannador®, has recently been shown to help symptoms in a UK trial.
Risks and side effects
Psychoactivity is proportional to how much THC each cannabis preparation contains. People with MS prescribed CB often report mild side-effects, while those with impaired cognition or depression may suffer more serious effects. Smoking cannabis rapidly increases blood THC concentrations, which then quickly fall due to metabolism and body fat distribution. This limits drug activity and any corresponding psychoactive effect. Smoking cannabis probably carries the same risk of lung injury as tobacco. Eating cannabis, however, causes THC levels to rise slowly and remain elevated, prolonging any psychological effects. THC can be detected in urine drug tests for long periods after use.
No deaths have been attributed to cannabis overdose. However, cognitive impairment means that its use should be avoided during potentially dangerous activities (such as driving). Risk of long-term psychiatric disturbance is controversial, but teenagers and chronic users may be the most vulnerable. Withdrawal symptoms can also occur.
Much debate surrounds the classification of cannabis as an illicit drug. It is currently illegal in many places around the world. It is important to know the law in your jurisdiction.
Conclusion
Further research will clarify the role of cannabis in MS, and drug development may reduce psychological side-effects. Current evidence supports CB treatment of MS-related pain, spasticity and bladder disturbance. Perhaps one of the most exciting areas of research is in establishing whether CB can slow the actual disease course of progressive MS. Overall, the future is bright for these naturallyoccurring molecules, which have been used in medicine since antiquity.
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| Editor’s note: Cannabis is illegal in some countries. Possession and use of cannabis can carry severe penalties.
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