CAMS Study

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CAMS Study

• A Multicentre Randomised Controlled Trial of
  Cannabinoids in Multiple Sclerosis

Principle Investigators Dr John Zajicek Dr Alan
Thompson Andrew Nunn Hilary Sanders
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Background - Multiple Sclerosis
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Background - MS

• 90 of patients with Multiple Sclerosis (MS) will
  experience symptoms of muscle spasticity and
  spasms.
• Current therapies for spasticity include
  baclofen, tizanidine, dantrolene and diazepam.
• All of these have significant side effects and
  limited efficacy.

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Background - MS

• Cannabis - widespread anecdotal reports of
  beneficial effects on
• spasticity
• tremor
• urinary disturbance
• pain.

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Background - MS

• Only two previous attempts at randomised double
  blind controlled studies of cannabinoids in total
  of 22 patients.
• Petro and Ellenberger, 1981
• 9 patients, 3 days.
• THC, double blinded crossover design
• significant reduction in spasticity score.

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Background - MS

• Ungerleider et al, 1988
• 13 patients, up to 6 weeks
• THC, double blinded crossover design
• significant reduction in patient rating of
  spasticity.
• Thus probably beneficial effect, but too small to
  generalise.

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Background - Cannabis
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Background - Cannabis

• Cannabis sativa - Cultivated Cannabis
• Many uses
• Rope
• Canvas
• Clothing
• Paper
• Medicinal

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Background - Cannabis

• Medicinal use for over 2000 years.
• First in the far east.
• Mentioned in western medical textbooks from the
  13th century onwards.
• The peak in its use was in the 19th century.

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Background - Cannabis

• Indications in 19th century.
• Dysmenorrhoea

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Background - Cannabis

• Other Indications.
• Pain
• Cramps
• Fever
• Vomiting
• Asthma
• Epilepsy.

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Background - Cannabis

• Also psychoactive properties.
• Recreational use.

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Background - Cannabis

• Fell out of use in early 20th century
• concern over its recreational use
• inconsistency in its preparation and absorption
• poor storage stability
• Formally banned in 1928
• Remained prescribable until 1971.

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Background - Cannabis

• Over 60 aromatic hydrocarbon compounds known as
  cannabinoids.
• Pharmacological effects mediated through
  cannabinoid receptors
• CB1 receptors are found widely in the nervous
  system
• CB2 receptors predominantly on B lymphocytes.

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Background - Cannabis

• THC - most important active cannabinoid.
• Available synthetically.
• Prescribable for nausea as nabilone.

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Background - Cannabis

• 1998 - House of Lords Select Committee report -
  Cannabis, the scientific and medical evidence.
• Positive about medicinal use.
• Advised further research before rescheduling of
  the drug.

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Trial Design
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Trial Design

• Multicentre randomised controlled trial.
• Comparing THC, cannabis oil and placebo.
• Coordinated from Plymouth
• Derriford will recruit approximately 100 patients
• 560 patients distributed across about 20 other
  centres nationwide.

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Trial Design - Centres
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Trial Design

• Two Phases
• Weeks 1-16
• All patients on drug
• Seven clinic visits
• Weeks 17-52
• Patient chooses whether to continue drug
• Three clinic visits

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Trial Design
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Primary Outcome Measures

• Ashworth Scale
• 5 grade assessment of spasticity on clinical
  examination.
• Rather coarse steps.
• Rather subjective.
• Reasonable inter- and intra- rater reliability.

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Secondary Outcome Measures

• Timed 10m walk
• Rivermead Mobility Index
• UK Neurological Disability Status Scale
• GHQ-30 (a quality of life questionnaire)
• Barthel Index (a measure of activities of daily
  living)
• 9 further category rating scales.

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Blinding

• Risk of unblinding of patient due to widely known
  side effects.
• Two study personnel.
• Treating physician
• Assessor (physician or physiotherapist)
• Degree of unblinding assessed at the end of the
  trial.

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Results

• Recruitment will start at beginning of 2001.
• Recruitment expected to last about 1 year.
• Results available 1 year after recruitment
  closes.
• Government has indicated that a successful trial
  may lead to rescheduling of cannabis.

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Further Information

• References general information
• www.cannabis-trial.plymouth.ac.uk
• email
• cannabis-trial_at_plymouth.ac.uk
• Telephone
• 01752 315250