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.
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
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."
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.
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:
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.
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."
& 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.
improvements in tremor reported by Meinck & Clifford
are dramatically demonstrated in fig 1 below.
1 - Effects of THC on tremor in MS patients
(1983) Meinck et al (1989)
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.
- 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.
Bowel Syndrome and Cannabinoids
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.
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
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.
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
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
9-THC, delta 9,11-THC, cannabinol and nabilone (but
not cannabidiol) exert an inhibitory effect on GI
transit and motility in rats".
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.
and Huntington"s Chorea
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.
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.
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.