Like so many other applications, there are numerous anecdotal reports from both patients and their carers who say that cannabis has proffered relief from a range of symptoms associated with MS, including tremor, spasticity and muscle pain. Evidence for the efficacy of cannabis in the relief of spasticity other than that found in MS is discussed in Spastic Conditions.
Meinck et al. () describe a case where the benefits of smoking cannabis reported by the patient — improvement in muscle tone, reflexes, spasticity, tremor and walking ability — were quantifiable in the laboratory and deteriorated on withdrawal. In a double-blind, placebo controlled trial of cannabis in 10 ambulant patients with MS, the drug impaired posture and balance although several patients reported an improvement in subjective feelings of well-being; a formal psychological assessment was not carried out.
Anecdotal evidence gathered from the testimonials of MS sufferers indicates that a considerable proportion obtain at least partial relief from night-time spasticity, and reduced muscle pain, tremor and depression.
Petro and Ellenburger reported a placebo-controlled trial of oral THC in 9, cannabis-naive patients with MS. Each patient was given a single dose of 5 or 10mg of THC or placebo on 3 successive days. Both doses of THC were reported to improve reflexes, muscle tone, mobility and spasticity, compared to placebo in some patients; but only 4 patients showed a ‘substantial’, objectively measured, improvement and just two of these claimed subjective improvement of their symptoms. One additional patient claimed subjective improvement only. Where an effect was observed, it reached a maximum at three hours and persisted for a further two hours.
In a similar trial using 5–15 mg doses of THC, two of eight patients showed objective as well as subjective improvement in tremor. An additional five patients claimed mild subjective improvements in tremor and general well-being, but this was not substantiated objectively. Interestingly, one of the patients had treated his tremor to his own satisfaction for 1 year prior to the study, without appreciating any decrease in response. The THC dosage form and any concurrent antitremor medication were not stated.
Ungerleider et al. () gave THC, 2.5–15 mg daily, to 13 patients with MS, refractory to treatment with standard muscle relaxants, in a double-blind, placebocontrolled, crossover trial. The patients reported subjective improvement when taking THC but the assessing neurologist could not distinguish between treatment and placebo groups. Reduction in spasticity, as rated by the patients, started at the 7.5 mg dose; all but one patient reported side effects at this dose and at higher doses, including dry mouth, weakness, dizziness and psychoactive effects; although the difference in mean side effect scores for THC and placebo did not reach statistical significance, few patients wished to continue THC therapy after the trial.
Most recently, Brenneisen et al. () demonstrated that THC might be useful in ms, given by both oral and rectal routes. The greater bioavailability of the rectal route led to greater efficacy.
Martyn et al. () report a case study, where a single MS patient was given nabilone, 1 mg every other day for 4 weeks, followed by a placebo administered in the same fashion over the same period. The trial was double-blind, and continued for a second eight-week cycle. Muscle spasm, nocturia and general feeling of well being were all improved during the active phases but disappeared rapidly when the placebo was given.
Overall, there is little data on which to make an assessment of the utility of cannabis or its derivatives in MS. Reports to date have been sparse, of poor quality, subjective, anecdotal and have taken little account of confounding factors such as the duration or severity of the illness and concurrent medication. Cases where improvement has been observed are more often than not heavily biased towards the subjective feelings of the patients and may simply be confirming the known mood altering, anxiolytic, sedative or analgesic properties of the drug.
Large scale studies are required, preferably with a cannabinoid derivative where the CNS effects have been dissociated from the peripheral actions and the formulation and dosing can be more closely controlled. It is interesting that the call for further investigation has not come just from the medical community, but also from MS sufferers themselves, in the form of the organisation ‘Alliance for Cannabis Therapeutics’ and in the UK, the MS Society. Even a small improvement may be of value in this distressing and multifaceted disorder; however, caution should be exercised in the use of any agent known to cause cognitive impairment, excessive muscle relaxation or central sedation in patients with organic CNS disease.
Mode of Action
Dystonias are known to be largely associated with raised levels of acetylcholine, dopamine and decreased GABA in the basal ganglia and cannabinoids appear to be capable of affecting all three neurotransmitters, possible by an inhibitory effect on the polysynaptic process: reducing acetylcholine turnover, decreasing ligand binding to dopamine receptors and increasing GABA turnover. It is possible that some, if not all of these effects could be operating in MS to improve motor co-ordination and relieve spasticity although the picture is far from clear.
Most recently, it has been suggested that cannabinoids may act in MS through an effect on specific cannabinoid (CB1) receptors in the brain and spinal chord to control movement and improve motor function (see «Advances in Cannabinoid Receptor Pharmacology»).