Multiple sclerosis is a disease of the brain and spinal cord caused by demyelination (loss of the insulating sheath) of nerve fibres, believed to be caused by some substance dissolving or breaking-up fatty tissue of the nerve-sheath. The condition is progressive but varies in intensity, with remission of symptoms and relapse commonly reported. Common symptoms include fatigue, balance problems, muscle weakness, incontinence, muscle spasms, pain and tremor.

Current treatments for MS are of little benefit, expensive, and with risks of side effects. alpha & beta-interferon, and corticosteroids have been found to have some value, but symptoms are poorly-controlled by existing medications, and no cure has been found. Many patients are unable to tolerate the side-effects of conventional medication

Anecdotal evidence. Grinspoon reports a number of anecdotal reports of dramatic improvement in MS symptoms attributed to marijuana (cannabis) use. Initially, these were unexpected findings following social use of the drug. In one account, Greg Paufler described a progressive degeneration, following onset of MS in 1973, to bedridden status, and severe side effects (dramatic weight gain, addiction to benzodiazepines) from prescribed medicines. Following several social "joints" one evening, he astonished family and friends by standing spontaneously for the first time in months. He subsequently found that his symptoms deteriorated without the drug, but improved dramatically during periods when he was smoking cannabis. Grinspoon reviewed further cases showing improvements in muscle spasms, tremor, continence, ataxia (loss of muscle control) and insomnia. Clare Hodges, an MS patient giving oral evidence to the House of Lords enquiry, reported cannabis "greatly relieved" physical symptoms including discomfort of bladder and spine, nausea and tremors, and stated "Cannabis helps my body relax, I function and move much easier. The physical effects are very clear, it is not just a vague feeling of well-being."

Animal studies - Scientists have developed animal models for MS in rats, mice and guinea-pigs in the form of an experimental autoimmune encephalomyelitis (EAE). In guinea-pigs, Lyman et al found 98% of animals treated with placebo died, whereas 95% of THC-treated animals survived the disease process, with much reduced inflammation of brain tissue. In rats, Wirguin et al found " 8THC significantly reduced neurological deficits in two strains of EAE inoculated rats. More recently, Molina-Holgado et al found anandamide (endogenous CB1 cannabinoid receptor agonist) reduced the effects of encephalomyelitis in mice, suggesting a receptor-mediated mode of action in arresting or reducing the autoimmune response considered to be involved in the MS disease process.

Human studies: In a study of 112 MS patients self-medicating with cannabis in the US and UK, Consroe et al reported that 70% of more respondents reported improvement in the following symptoms:

The authors considered these reports "strongly suggested cannabinoids may significantly relieve symptoms of MS, particularly spasticity and pain", and provided sufficient grounds for a properly controlled clinical trial to test such claims objectively and conclusively.

 Meinck et al reported "The chronic motor handicaps of a 30-year-old multiple sclerosis patient acutely improved while he smoked a marihuana cigarette. This effect was quantitatively assessed by means of clinical rating, electromyographic investigation of the leg flexor reflexes and electromagnetic recording of the hand action tremor. It is concluded that cannabinoids may have powerful beneficial effects on both spasticity and ataxia that warrant further evaluation."

 Petro & Ellenberger, in a small double-blind clinical trial found 10mg THC significantly (p<.01) reduced spasticity in patients with MS or similar conditions, compared to placebo. In an earlier double-blind crossover trial, Ungerleider et al reported "At doses greater than 7.5 mg there was significant improvement in patient ratings of spasticity compared to placebo. These positive findings in a treatment failure population suggest a role for THC in the treatment of spasticity in multiple sclerosis." Clifford, in a trial involving 8 patients severely disabled with tremor and ataxia, reported significant improvement in two patients.

 The improvements in tremor reported by Meinck & Clifford are dramatically demonstrated in fig 1 below.

In a pilot study involving two patients, Brenneison et al reported "Oral and rectal THC reduced at a progressive stage of illness the spasticity, rigidity, and pain, resulting in improved active and passive mobility." In a single case double-blind trial, Maurer et al found THC "showed a significant beneficial effect on spasticity. In the dosage of THC used no altered consciousness occurred." Consroe et al reported cannabidiol (CBD) to produce dose-related improvements in dystonic movement disorders. Malec et al found spinal cord injured persons reported decreased spasticity with marijuana use. Other papers have also reported potential benefits of cannabinoids, including crude marijuana, and the synthetic Nabilone, where Martyn et al found clear improvement in well-being, reduced pain from muscles spasm, and reduced frequency of nocturia during the treatment condition (1mg Nabilone every other day) compared to worsening of symptoms in "no treatment" or placebo conditions.

Summary - Multiple Sclerosis is a disease for which conventional medication provides little benefit. There is a wealth of anecdotal evidence from MS patients reporting dramatic improvement in symptoms following illicit use of cannabis, and the limited clinical trials which have taken place to date have shown that, at least in some patients, symptoms such as pain, ataxia, spasticity and tremor can be dramatically improved. Recent animal research has suggested a direct CB1-receptor mediated immunosuppressive effect may delay the neurodegenerative process in MS-like animal models, although this may suggest longer term benefits, it would not explain the acute improvement in symptoms reported by many MS patients following cannabis use. The House of Lords Science & Technology Committee recommended that clinical trials of cannabinoids in the treatment of MS be undertaken as a matter of urgency, and that pending the award of product licences, doctors should be allowed to prescribe cannabis or cannabis resin as an unlicensed medicine on a named-patient basis for patients, including MS sufferers.

Irritable Bowel Syndrome and Cannabinoids

Although the use of cannabinoids as antiemetics (anti-nausea) is well-established, with Dronabinol available to stimulate appetite and counter effects of cancer chemotherapy, the effect of cannabinoids on disorders of the gut has not been extensively studied. However the current state of knowledge of the biochemistry of cannabinoids is increasing at an exponential rate and, with discoveries of cannabinoid receptors in unexpected areas of the body, new potential research/treatment avenues are appearing at an increasing rate.

Grinspoon reports anecdotal use of cannabis to control bowel movements in multiple sclerosis, and relief from the symptoms of Crohn"s disease. Mikuriya records irritable bowel syndrome, as well as other inflammatory gastrointestinal conditions (principally among AIDS patients), as one of a wide variety of conditions for which cannabis has been prescribed or recommended for therapeutic use in California. There are no clinical trials currently published, and consequently use for the treatment of irritable bowel syndrome would represent at best an experimental therapy.

However, there does appear to be some scientific support for any claimed therapeutic benefits from the research literature concerning the actions and metabolism of cannabinoids and cannabinoid receptors. The wall of the intestine is composed of a type of muscle known as "smooth muscle", also found lining the walls of arteries and in other involuntary functions.

Rosell et al first demonstrated that cannabinoids inhibit contractions of the small intestine in the rat. Pertwee et al established the presence of cannabinoid (CB1) receptors within the guinea-pig intestine and Kazuhisa et al established the presence of enzymes break down anandamide (the endogenous cannabinoid CB1-agonist) within the small intestine. The smooth muscle-relaxant properties of cannabinoids are so well established that preparations of guinea-pig intestine are routinely used as an in vitro screening tool to test the potency and function of novel cannabinoids.

Shook & Burks found that THC reduced the frequency of intestinal contractions, and reduced the flow of food in the small intestine, without altering basal tone, and concluded that

"...delta 9-THC, delta 9,11-THC, cannabinol and nabilone (but not cannabidiol) exert an inhibitory effect on GI transit and motility in rats".

Cadas et al reported that a gut enzyme (vasoactive intestinal peptide) may regulate the precursor chemical to anandamide (which activates cannabinoid CB1 receptors) and N-palmitoylethanolamine (which activates a CB2-like receptor subtype), suggesting that endogenous cannabinoids may play a role in regulating the activity of the gut.

We are not aware of any controlled studies of medical use of cannabis in the treatment of irritable bowel syndrome, there appears to be sufficient evidence of the potential efficacy of cannabis in reducing intestinal spasms to merit further research into this and related indications. Any symptomatic relief obtained from smoking cannabis would occur far more rapidly than with oral preparations.

Cannabis and Huntington"s Chorea

Huntington"s chorea is a fatal degenerative condition inherited via sex chromosomes. It is rare in women who may carry the disease, which usually develops in middle-aged males. There is a gradual loss of mental and cognitive function, commonly associated with depression and progressive loss of voluntary motor control, leading to an increasing dependency on others.

The condition is incurable, although neuroleptic drugs such as haloperidol may be used to control symptoms. It has been suggested that the neuronal degeneration caused by the disease results from excess free-radicals oxidation or glutamate. Skaper et al showed cannabinoids, but not anandamide, to protect against glutamate-mediated neurotoxicity. Peyser et al concluded "Antioxidant therapy may slow the rate of motor decline early in the course of Huntington's disease. " Hampson et al found THC and CBD to be "neuroprotective anti-oxidants" improving the recovery prospects of stroke patients by reducing glutamate toxicity, and considered their results to suggest the neuroprotective action not to be receptor-dependent. However Consroe et al found no positive or negative effect of CBD in Huntington"s patients, although this may be due to the degree of neuronal damage already present at the outset of the trial.

Richfield et al demonstrated there to be a selective loss of cannabinoid receptors in specific regions of the brain called the corpus striatum and globus pallidus, and Glass et al showed a "massive loss - 97.5%) of cannabinoid receptors in the substantia nigra (within spinal cord) of Huntington"s patients. N-methyl-d-aspartate (NMDA) receptor antagonists have been shown to delay neurodegeneration, and a synthetic cannabinoid (+)-HU-210 has been found to be a potent antagonist of the NMDA receptor, "giving it a potential for use in ... neurodegenerative disorders".

This is an emerging area of research and clearly more research is needed. However the massive depletion of cannabinoid receptors, coupled with the neuroprotective effects of cannabidiol, would suggest cannabinoids potentially to have a major future role in treating symptomatology of Huntington"s chorea (e.g. uncontrolled muscle spasms/movements) by direct stimulation of remaining receptors by THC or other CB1 receptor agonists; and/or by delaying the development of the disease due to the neuroprotective effects of THC and CBD.