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 respo nses to a questionnaire by 112 patients with MS who self-medicated with can nabis. The preclinical data come from animal experiments showing that canna binoid receptor agonists are antinociceptive and can depress motor function , reduce the severity of primary generalised dystonia, and decrease inflamm ation and the intensity of behavioural signs of experimental autoimmune enc ephalomyelitis. The clinical data derive from 7 clinical trials, albeit inv olving 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 sympt oms 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 tr ial to attempt to provide an objective and conclusive answer to the questio ns of whether cannabis and cannabinoids are effective in MS and, if they ar e, whether these effects are achievable at dose levels that do not provoke unacceptable adverse effects. Likely drug candidates for a clinical trial i nclude Delta(9)-THC and nabilone, both of which are already licensed medici nes. When taken orally, Delta(9)-THC seems to undergo variable absorption a nd to have a narrow 'therapeutic window'. This makes it difficult to predic t an oral dose that will be both effective and tolerable, so prompting a ne ed far better cannabinoid formulations, cannabinoid vehicles and modes of a dministration. There is also a need to establish whether cannabis has any therapeutic adva ntages over individual cannabinoids such as Delta(9)-THC and, if so, to inv estigate the basis for this. In addition, it will be worth seeking out a wa y of separating the therapeutic properties of cannabinoids from their unwan ted effects, particularly their psychotropic effects, and several strategie s for achieving this goal are described. To succeed, any clinical study with cannabinoids will require sufficient fu nding, the use of adequate outcome measures, and the committed involvement of scientists and physicians who have appropriate cannabinoid and clinical expertise.