1. © CAMS Trial 2001 CAMS Study A Multicentre Randomised Controlled Trial of Cannabinoids in Multiple Sclerosis Principle Investigators Dr John Zajicek Dr Alan Thompson Andrew Nunn Hilary Sanders

2. © CAMS Trial 2001 Background - Multiple Sclerosis

3. © CAMS Trial 2001 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.

4. © CAMS Trial 2001 Background - MS Cannabis - widespread anecdotal reports of beneficial effects on –spasticity –tremor –urinary disturbance –pain.

5. © CAMS Trial 2001 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.

6. © CAMS Trial 2001 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.

7. © CAMS Trial 2001 Background - Cannabis

8. © CAMS Trial 2001 Background - Cannabis Cannabis sativa - “Cultivated Cannabis” Many uses –Rope –Canvas –Clothing –Paper –Medicinal

9. © CAMS Trial 2001 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.

10. © CAMS Trial 2001 Background - Cannabis Indications in 19th century. –Dysmenorrhoea

11. © CAMS Trial 2001 Background - Cannabis Other Indications. –Pain –Cramps –Fever –Vomiting –Asthma –Epilepsy.

12. © CAMS Trial 2001 Background - Cannabis Also psychoactive properties. Recreational use.

13. © CAMS Trial 2001 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.

14. © CAMS Trial 2001 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.

15. © CAMS Trial 2001 Background - Cannabis THC - most important active cannabinoid. Available synthetically. Prescribable for nausea as nabilone.

16. © CAMS Trial 2001 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.

17. © CAMS Trial 2001 Trial Design

18. © CAMS Trial 2001 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.

19. © CAMS Trial 2001 Trial Design - Centres

20. © CAMS Trial 2001 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

21. © CAMS Trial 2001 Trial Design

22. © CAMS Trial 2001 Primary Outcome Measures Ashworth Scale –5 grade assessment of spasticity on clinical examination. –Rather coarse steps. –Rather subjective. –Reasonable inter- and intra- rater reliability.

23. © CAMS Trial 2001 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.

24. © CAMS Trial 2001 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.

25. © CAMS Trial 2001 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.

26. © CAMS Trial 2001 Further Information References & general information: –www.cannabis-trial.plymouth.ac.uk email: –cannabis-trial@plymouth.ac.uk Telephone: –01752 315250