Randomized, controlled trial of cannabis-based medicine in central pain in MS


David J. Rog, BMBS, Turo J. Nurmikko, PhD, Tim Friede, PhD and Carolyn
A. Young, MD
>>From the Walton Centre for Neurology and Neurosurgery (Drs. Rog and
Young), Liverpool, University of Liverpool (Drs. Rog, Nurmikko, and
Young); Pain Research Institute (Dr. Nurmikko), Liverpool; Medical
Statistics Unit (Dr. Friede), Lancaster University, Lancaster, United
Kingdom.

Background: Central pain in multiple sclerosis (MS) is common and often
refractory to treatment.

Methods: We conducted a single-center, 5-week (1-week run-in, 4-week
treatment), randomized, double-blind, placebo-controlled,
parallel-group trial in 66 patients with MS and central pain states (59
dysesthetic, seven painful spasms) of a whole-plant cannabis-based
medicine (CBM), containing delta-9-tetrahydrocannabinol:cannabidiol
(THC:CBD) delivered via an oromucosal spray, as adjunctive analgesic
treatment. Each spray delivered 2.7 mg of THC and 2.5 of CBD, and
patients could gradually self-titrate to a maximum of 48 sprays in 24
hours.

Results: Sixty-four patients (97%) completed the trial, 34 received
CBM. In week 4, the mean number of daily sprays taken of CBM (n = 32)
was 9.6 (range 2 to 25, SD = 6.0) and of placebo (n = 31) was 19.1
(range 1 to 47, SD = 12.9). Pain and sleep disturbance were recorded
daily on an 11-point numerical rating scale. CBM was superior to
placebo in reducing the mean intensity of pain (CBM mean change -2.7,
95% CI: -3.4 to -2.0, placebo -1.4 95% CI: -2.0 to -0.8,
comparison between groups, p = 0.005) and sleep disturbance (CBM mean
change -2.5, 95% CI: -3.4 to -1.7, placebo -0.8, 95% CI: -1.5
to -0.1, comparison between groups, p = 0.003). CBM was generally
well tolerated, although more patients on CBM than placebo reported
dizziness, dry mouth, and somnolence. Cognitive side effects were
limited to long-term memory storage.

Conclusions: Cannabis-based medicine is effective in reducing pain and
sleep disturbance in patients with multiple sclerosis related central
neuropathic pain and is mostly well tolerated.



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Additional material related to this article can be found on the
Neurology Web site. Go to www.neurology.org. and scroll down the Table
of Contents for the September 27 issue to find the link for this
article.

Disclosure: David J. Rog, BMBS, Carolyn A. Young, MD, and Turo J.
Nurmikko, PhD, contributed to the conception and design of this study
and the drafting and revision of the paper. Drs. Rog and Young
participated in the acquisition of trial data. Dr. Friede independently
analyzed the study data and contributed to the drafting and revision of
the paper. Dr. Rog has accepted travel and accommodation expenses from
GW Pharma to attend an Investigator's Meeting (less than $10,000) and
his salary was paid from a research fund to which GW Pharma contributed
(in excess of $10,000). Dr. Friede has no conflicts of interest; he is
currently employed by Novartis Pharma, Basle, Switzerland. Drs. Young
and Nurmikko have both received funding for research (in excess of
$10,000) from GW Pharma and Dr. Nurmikko has also received an
honorarium (less than $10,000) for speaking from GW Pharma.

GW Pharmaceuticals sponsored the trial, contributed to study design,
provided trial medication and matching placebo and collected the data.
GW Pharma Ltd. has contracted data handling and analysis to a contract
research organization. The authors have received full access to the
data and conducted an independent analysis. GW and Bayer
Pharmaceuticals have had the opportunity to review the manuscript of
the paper, but decision to publish rests with the authors.

Received January 15, 2005. Accepted in final form June 9, 2005.

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