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Introduction: Patients with multiple sclerosis (MS) usually experience a range of impairments, of which muscle spasticity is often prominent and disabling. Following completion of a double-blind, placebo-controlled trial of a cannabis-based medicinal extract (CBME) in the symptomatic treatment of MS, patients were given the option to enter a long-term follow-up trial to determine whether benefits seen following CBME might be maintained over many months of treatment.
Methods: Acute study: a randomised, placebo-controlled, double-blind parallel group study over six weeks of treatment at three centres in the UK. Eligible patients were experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. CBME (Sativex) containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and placebo was delivered by oro-mucosal spray in a self-titrated dose up to a maximum of 48 sprays (120mg of THC and CBD) daily in divided doses. Primary symptoms were measured by 100 mm visual analogue scale (VAS).
Long-term study: Patients completing the acute study were eligible for inclusion in this open label study. Participating patients attended the clinic at eight-weekly intervals, completed a weekly symptom and intoxication diary using VAS, and recorded daily CBME doses.
Results: 160 patients completed the acute study, with daily doses following self-titration averaging 15 sprays of CBME (37.5mg of THC and CBD) and 26 for placebo. In the 39 patients with spasticity as their primary symptom VAS spasticity scores fell by 31.2mm following CBME and by 8.4mm following placebo (95% CI for difference —35.52, -10.07; SE 6.26; p = 0.001). Diary scores produced a similar result (p = 0.009). 137 patients entered the long-term study and were followed for an average of 434 days (range 21-814), and 58 (42.3%) withdrew for the following reasons: lack of efficacy 24; adverse events 17; withdrawn consent 6; lost to follow-up 3; other 8. Sixty-six patients with spasticity completed 82 weeks CBME treatment. At entry to the acute study this group had a mean VAS spasticity score of 69.5, which had reduced to 34.2 on entry into the long-term study. After 82 weeks, the mean score was 31.8 and average daily dose had reduced marginally from 12 sprays on entry to 10 sprays at the last assessment. Similar reductions were seen in VAS measures of bladder-related problems, muscle spasm and pain in the long-term patients. Sudden interruption of CBME for two weeks in a sub-group of 25 patients did not result in a consistent withdrawal syndrome. Commonest unwanted effects were oral irritation from the ethanolic spray, dizziness, diarrhoea and nausea but these were generally mild to moderate in intensity and well tolerated.
Conclusion: Beneficial effects of CBME (Sativex) on spasticity (and other symptoms) in MS seem to be maintained over long-term treatment, with no evidence of tolerance.
Source: Clinical Studies and Case Reports
Methods: Acute study: a randomised, placebo-controlled, double-blind parallel group study over six weeks of treatment at three centres in the UK. Eligible patients were experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. CBME (Sativex) containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and placebo was delivered by oro-mucosal spray in a self-titrated dose up to a maximum of 48 sprays (120mg of THC and CBD) daily in divided doses. Primary symptoms were measured by 100 mm visual analogue scale (VAS).
Long-term study: Patients completing the acute study were eligible for inclusion in this open label study. Participating patients attended the clinic at eight-weekly intervals, completed a weekly symptom and intoxication diary using VAS, and recorded daily CBME doses.
Results: 160 patients completed the acute study, with daily doses following self-titration averaging 15 sprays of CBME (37.5mg of THC and CBD) and 26 for placebo. In the 39 patients with spasticity as their primary symptom VAS spasticity scores fell by 31.2mm following CBME and by 8.4mm following placebo (95% CI for difference —35.52, -10.07; SE 6.26; p = 0.001). Diary scores produced a similar result (p = 0.009). 137 patients entered the long-term study and were followed for an average of 434 days (range 21-814), and 58 (42.3%) withdrew for the following reasons: lack of efficacy 24; adverse events 17; withdrawn consent 6; lost to follow-up 3; other 8. Sixty-six patients with spasticity completed 82 weeks CBME treatment. At entry to the acute study this group had a mean VAS spasticity score of 69.5, which had reduced to 34.2 on entry into the long-term study. After 82 weeks, the mean score was 31.8 and average daily dose had reduced marginally from 12 sprays on entry to 10 sprays at the last assessment. Similar reductions were seen in VAS measures of bladder-related problems, muscle spasm and pain in the long-term patients. Sudden interruption of CBME for two weeks in a sub-group of 25 patients did not result in a consistent withdrawal syndrome. Commonest unwanted effects were oral irritation from the ethanolic spray, dizziness, diarrhoea and nausea but these were generally mild to moderate in intensity and well tolerated.
Conclusion: Beneficial effects of CBME (Sativex) on spasticity (and other symptoms) in MS seem to be maintained over long-term treatment, with no evidence of tolerance.
Source: Clinical Studies and Case Reports
