due to recruitment problems / based on recommendation of Independent Review Board

Study Objectives: To determine the efficacy and safety of a standardised extract of Cannabis sativa given orally 2 times daily as compared to placebo for the relief of muscle stiffness and pain in multiple sclerosis for a period of 12 weeks.

Study Patients: 400 patients with multiple sclerosis (age 18-64, stable disease during previous 6 months, ambulatory or not, antispasticity medication and physiotherapy stabilised ≥ 30 days) with experiencing muscle stiffness ≥ 4 on a 11-point numerical Likert scale at baseline.

Study treatment:

Group 1: Cannabis extract (delta-9-THC 2.5mg, CBD 1.25 mg per capsule), flexible dosing between 5 mg and 25 mg THC/d, administered twice daily, additionally to previous antispasticity and analgesic medication.

Group 2: Matched placebo, twice daily, additionally to previous antispasticity and analgesic medication.

Treatment Schedule: Start dose 5 mg THC/d, individual dose titration with increase of 5 mg THC every 3 days, maximal total daily dose 25 mg THC, administered as 2 equal doses based on tolerability. Treatment duration: 12 weeks.

Study sites: 20 neurological clinics in the United Kingdom.

Inclusion Criteria:

• Signed informed consent.
• Diagnosis of MS according to McDonald criteria.
• Current muscle stiffness ≥ 4 on a 11-point categorical rating scale.
• On-going troublesome muscle stiffness for at least 3 months.
• Stable disease for the previous 6 months.
• Antispasticity medication and physiotherapy stabilised for the last 30 days.
• Patients may be ambulatory or not.
• Age 18-64.

Exclusion Criteria:

• Immunosuppressants which may affect spasticity (including corticosteroids and interferon but ex-cluding azathioprine) taken currently or in previous 30 days
• Past or present history of psychotic illness.
• Open/infected pressure sores or other source of chronic infection.
• Significant fixed tendon contractures.
• Severe cognitive impairment such that the patient is unable to provide informed consent.
• History of clinically important renal, cardiovascular or neurol. diseases (apart from MS).
• Malignancy within the past 2 years.
• Cannabinoids taken currently or in previous 30 days.
• Positive qualitative urinary test on cannabinoids at screening visit. (In this case a patient will be allowed to repeat the test at a second screening visit later.)
• Known hypersensitivity to cannabinoids.
• Current drug abuse, including alcohol abuse.
• Laboratory parameters outside the following limits:

Creatinine > 3x upper limit of normal Bilirubine > 3x upper limit of normal Transaminases > 5 x upper limit of normal

• Anticipated immunisations within the 12 weeks of trial participation.
• Other problems likely to make participation difficult at the discretion of the neurologist.
• Women who are pregnant, lactating or not using adequate contraception.
• Participation in other treatment studies currently or within the previous month.