"Cannabis-Based Treatment Effective in Neuropathic Pain and Spasticity: Presented at EFNS"
By Chris Berrie
GLASGOW, UK -- September 8, 2006 -- The investigative agent Sativex, which contains a standardised formulation of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), is efficacious and well tolerated during long-term use in patients with neuropathic pain (NP) of various aetiologies or with spasticity due to multiple sclerosis (MS), according to a placebo-controlled, clinical study.
Mick Serpell, MBCHB, coinvestigator and senior lecturer, department of anaesthesia and pain medicine, Western Infirmary, Glasgow University, Glasgow, United Kingdom, presented the findings here on September 4[th at the 10th Congress of the European Federation of Neurological Societies (EFNS).
Sativex contains standardised levels of THC and CBD that are produced from selected strains of Cannabis sativa. The agent is formulated into a spray that is designed to deliver 2.7 mg of THC and 2.5 mg of CBD per 100 mcL when used for oromucosal administration.
The researchers evaluated the effects Sativex in an open-label extension of 4 clinical, double-blind, randomised, controlled trials, at the end of which patients were offered the opportunity to go into the open-label extension, as a 1-year follow-up, to evaluate long-term patient tolerance and side effects, the study's primary objective.
The secondary objectives related to possible tolerance to Sativex, as assessed by its efficacy towards NP of various aetiologies and spasticity due to MS.
The cohort consisted of 507 patients with a mean age of 50 years (male, 43%), who represented 74% of those who had participated in the parent eligibility trials. These were primarily of Caucasian ethnic origins (96%), and 47% had had previous cannabis use. Of these, 262 (52%) withdrew from the study for a range of reasons, where 85 (17%) were due to all causality adverse events from the study medication.
Sativex was applied as a sublingual spray, with subject self-titration of the dose within the maximum permissible use of 8 actuations in a 3-hour period, and 48 in 24 hours. This led to Sativex use of from 5 to 9 actuations per day, where the mean dose remained relatively stable to 52 weeks, which indicated the absence of development of tolerance.
For the 2 study groupings of pain (centre NP; pain in MS), symptom severity numeric rating scale (NRS) scores showed an initial improvement in the pain over that seen in the parent trial, and this was maintained up to 100 weeks. Similarly, bladder dysfunction severity NRS score and spasticity severity NRS score both showed initial and maintained benefits of Sativex up to 44 and 92 weeks.
Sleep quality was also rated across these patients with NP and MS, with the majority also experiencing initial (to week 4) improvements in sleep quality that were maintained and further improved to 52 weeks.
Over this long-term use of Sativex, 94% of subjects experienced at least 1 adverse event, with the majority of adverse events being mild or moderate in severity, the researchers said.
Treatment-related adverse events were seen in 85% of subjects, with the most prevalent being dizziness (26.8%), nausea (12.6%), fatigue (9.1%), diarrhoea (8.1%), somnolence (7.9%), dry mouth (7.7%), dysgensia (7.5%), and headache (6.5%). The greatest proportion of these adverse events was seen in subjects with nervous system disorders (49.5%), gastrointestinal disorders (44.6%), and general disorders, and administration site conditions (35.7%).
While 14.6% of subjects experienced serious adverse events, 3.2% were considered to be treatment related, the most common of which were gastrointestinal disorders. Of the 4 deaths that occurred during the study, 2 were not medication related, 1 was from lung cancer after Sativex discontinuation, and 1 patient was aspiration pneumonia, which was considered to be Sativex related.
There were no significant changes from baseline in laboratory parameters (biochemistry, haematology, urine analysis), and there were no long-term effects on vital signs and electrocardiograms.
Dr. Serpell stressed that the benefits seen with Sativex in these patients groups were maintained for up to 1 year without development of tolerance, and with acceptable safety and tolerability.
This study was sponsored by GW Pharma Ltd.
[Presentation title: Long-Term, Open-Label Treatment With Sativex a Cannabis-Based Medicine, in Neuropathic Pain of Various Aetiologies, and Spasticity Due to Multiple Sclerosis. Abstract P2261]
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