A study to compare the efficacy of GW-1000-02 \[named Sativex® in Canada and also named Sativex® Oromucosal Spray\] with placebo in relieving five key symptoms of Multiple Sclerosis after six weeks of therapy.
The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5-120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient's most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P =0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild.
Conference»IACM 3rd Conference on Cannabinoids in Medicine
Year»2005
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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 doubleblind, 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.
The object of this study was to monitor the safety and efficacy of long-term use of an oromucosal cannabis-based medicine (CBM) in patients with multiple sclerosis (MS). A total of 137 MS patients with symptoms not controlled satisfactorily using standard drugs entered this open-label trial following a 10-week, placebo-controlled study. Patients were assessed every eight weeks using visual analogue scales and diary scores of main symptoms, and were followed for an average of 434 days (range: 21 -814). A total of 58 patients (42.3%) withdrew due to lack of efficacy (24); adverse events (17); withdrew consent (6); lost to follow-up (3); and other (8). Patients reported 292 unwanted effects, of which 251 (86%) were mild to moderate, including oral pain (28), dizziness (20), diarrhoea (17), nausea (15) and oromucosal disorder (12). Three patients had five 'serious adverse events' between them--two seizures, one fall, one aspiration pneumonia, one gastroenteritis. Four patients had first-ever seizures. The improvements recorded and dosage taken in the acute study remained stable. Planned, sudden interruption of CBM for two weeks in 25 patients (of 62 approached) did not cause a consistent withdrawal syndrome, although 11 (46%) patients reported at least one of--tiredness, interrupted sleep, hot and cold flushes, mood alteration, reduced appetite, emotional lability, intoxication or vivid dreams. Twenty-two (88%) patients re-started CBM treatment. We conclude that long-term use of an oromucosal CBM (Sativex) maintains its effect in those patients who perceive initial benefit. The precise nature and rate of risks with long-term use, especially epilepsy, will require larger and longer-term studies.
A study to compare the efficacy of GW-1000-02 \[named Sativex® in Canada and also named Sativex® Oromucosal Spray\] with placebo in relieving five key symptoms of Multiple Sclerosis after six weeks of therapy.
