gw-1000 and Peripheral-Nervous-System-Diseases

Cannabinoids are known to have analgesic properties. We evaluated the effect of oro-mucosal sativex, (THC: CBD), an endocannabinoid system modulator, on pain and allodynia, in 125 patients with neuropathic pain of peripheral origin in a five-week, randomised, double-blind, placebo-controlled, parallel design trial. Patients remained on their existing stable analgesia. A self-titrating regimen was used to optimise drug administration. Sixty-three patients were randomised to receive sativex and 62 placebo. The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mean adjusted scores -1.48 points vs. -0.52 points on a 0-10 Numerical Rating Scale (p=0.004; 95% CI: -1.59, -0.32). Improvements in Neuropathic Pain Scale composite score (p=0.007), sleep NRS (p=0.001), dynamic allodynia (p=0.042), punctate allodynia (p=0.021), Pain Disability Index (p=0.003) and Patient's Global Impression of Change (p<0.001) were similarly greater on sativex vs. placebo. Sedative and gastrointestinal side effects were reported more commonly by patients on active medication. Of all participants, 18% on sativex and 3% on placebo withdrew during the study. An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Analgesics; Cannabidiol; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Hyperesthesia; Male; Middle Aged; Neuralgia; Pain Measurement; Peripheral Nervous System Diseases; Plant Extracts; Psychomotor Performance; Time Factors; Treatment Outcome

GW Pharmaceuticals is developing GW-1000 (Sativex), a narrow ratio delta9-tetrahydrocannabinol:cannabidiol product for the potential treatment of multiple sclerosis, spinal cord injury, neurogenic pain and peripheral neuropathy. In March 2003, the company filed for approval for the treatment of MS with the UK Medicines Control Agency, and in May 2004, filed for new drug submission with Health Canada.

Topics: Administration, Oral; Analgesics; Animals; Biological Availability; Canada; Cannabidiol; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dronabinol; Drug Approval; Drug Combinations; Drug Evaluation, Preclinical; Drug Industry; Humans; Hyperalgesia; Investigational New Drug Application; Mice; Molecular Structure; Multiple Sclerosis; Patents as Topic; Peripheral Nervous System Diseases; Phytotherapy; Plant Extracts; Plant Preparations; Randomized Controlled Trials as Topic; Spinal Cord Injuries; Structure-Activity Relationship