Clinical Studies and Case Reports

Sativex® in the Treatment of Central Neuropathic Pain due to Spinal Cord Injury:
A Randomised Controlled Study
Berman JS1 & the Sativex Spinal Cord Injury Study Group, Bosworth T2, Guy GW2, Stott CG2
1Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, Middlesex, HA7 4LP,UK,
2GW Pharma Ltd, Porton Down Science Park, Salisbury, Wiltshire, SP4 0JQ.
Background Little is known of the efficacy and safety of cannabinoids (including delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)) in the treatment of central neuropathic pain (CNP) due to spinal cord injury (SCI).
Aim: To assess the efficacy and safety of Sativex in the relief of neuropathic pain due to spinal cord injury.
Methods Sativex® (THC:CBD), an endocannabinoid system modulator, was investigated as an-add on treatment in a 3-week, multi-centre, randomised, double-blind, placebo-controlled trial of 117 SCI patients with CNP, who did not have an adequate response to existing medications.
Subjects had CNP, of at least six months duration, associated with SCI. Subjects also had a mean CNP severity score of at least 4 on an 11-point Numeric Rating Scale (0-10 NRS) during their last 7 days in the baseline period.
Each Sativex oromucosal spray (100l), delivered 2.7mg THC and 2.5mg CBD. Patients self-titrated their dosage up to a daily maximum of 48 sprays per day.
The primary endpoint was the mean difference in the change from baseline mean Numerical Rating Scale (NRS) pain scores. Secondary endpoints included Brief Pain Inventory (BPI), Patient’s Global Impression of Change (PGIC), sleep disturbance, escape analgesic usage, Short Orientation-Memory-Concentration test (SOMC), Caregiver Strain Index (CSI) and Spitzer Quality of Life Index (Spitzer QLI).
Results
Of the 117 randomised (n=57 Sativex, n=60 placebo), 11 patients withdrew during the study, with the remaining 106 completing treatment. The mean number of sprays per day of study treatment was 9.5 sprays for Sativex and 19.2 sprays for placebo.
Sativex and placebo produced similar reductions in mean NRS pain score from baseline but this treatment difference was not statistically significant (NRS pain score: Sativex: -1.08, placebo: -1.00; p=0.708) either in the ITT analysis (p = 0.708) or the Per Protocol analysis (p=0.878).
Statistically significant treatment differences in pain relief in favour of Sativex was detected using the BPI. (Total BPI Score (1.93 points, p=0.032), Mean BPI (0.46 points, p=0.040) and Least Pain in the last 24 hours (0.79 points, p=0.007)).
The analysis of the PGIC was also statistically in favour of Sativex: 54.5% of patients reported that their condition had ‘improved’ compared to those who had “not improved” (20.7%) was (p<0.001) with an odds ratio of 3.40 (p=0.001). Outcomes for other secondary endpoints were not significant.
Sativex was generally well tolerated. Most adverse events (AEs) were reported as mild or moderate. The most common treatment related AE was dizziness (Sativex: 24.6%; placebo: 6.7%).
Conclusion
In this study, although Sativex produced a reduction from baseline in NRS pain score, the difference from placebo was not statistically significant. Some secondary pain-related endpoints did provide statistically significant evidence of analgesic effect and the study medication was generally well tolerated.

Declaration: Dr. JS Berman was a paid Chief Investigator for this study, sponsored by GW Pharma Ltd.