Prescribing cannabinoids for multiple sclerosis - Current issues

Anecdotal evidence and preclinical and clinical data indicate that cannabis and individual cannabinoids can suppress muscle spasticity/spasm and pain associated with multiple sclerosis (MS). Anecdotal data come from the responses to a questionnaire by 112 patients with MS who self-medicated with cannabis. The preclinical data come from animal experiments showing that cannabinoid receptor agonists are antinociceptive and can depress motor function, reduce the severity of primary generalised dystonia, and decrease inflammation and the intensity of behavioural signs of experimental autoimmune encephalomyelitis. The clinical data derive from 7 clinical trials, albeit involving small numbers of patients, which indicate that cannabis itself, the cannabinoid Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and the synthetic analogue of Delta(9)-THC nabilone can reduce the intensity of several symptoms in patients with MS or spinal cord injury, including spasticity, pain, tremor and nocturia.

These data provide sufficient evidence to warrant a large scale clinical trial to attempt to provide an objective and conclusive answer to the questions of whether cannabis and cannabinoids are effective in MS and, if they are, whether these effects are achievable at dose levels that do not provoke unacceptable adverse effects. Likely drug candidates for a clinical trial include Delta(9)-THC and nabilone, both of which are already licensed medicines. When taken orally, Delta(9)-THC seems to undergo variable absorption and to have a narrow 'therapeutic window'. This makes it difficult to predict an oral dose that will be both effective and tolerable, so prompting a need far better cannabinoid formulations, cannabinoid vehicles and modes of administration.

There is also a need to establish whether cannabis has any therapeutic advantages over individual cannabinoids such as Delta(9)-THC and, if so, to investigate the basis for this. In addition, it will be worth seeking out a way of separating the therapeutic properties of cannabinoids from their unwanted effects, particularly their psychotropic effects, and several strategies for achieving this goal are described.

To succeed, any clinical study with cannabinoids will require sufficient funding, the use of adequate outcome measures, and the committed involvement of scientists and physicians who have appropriate cannabinoid and clinical expertise.