A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment

Authors


  • Sativex, a THC/CBD fixed dose combination oromucosal spray, does not have an INN. Nabiximols is the FDA US Adopted Name (USAN)
  • ClinicalTrials.gov registration number: NCT00710554.
  • Funding sources

    This study was sponsored by GW Pharma Ltd (GW). GW was involved in the study design, data collection and analysis, as well as in the preparation of this manuscript and publication decisions.

  • Conflicts of interest

    M. Serpell, S. Ratcliffe, J. Hovorka, M. Schofield and E. Ehler were all investigators in this study and received investigator fees from GW accordingly for their participation in the study. GW medical writers L. Taylor and H. Lauder undertook the initial compilation and quality control review of the manuscript. Together with the other authors, the target journal was then agreed and all authors reviewed and contributed to the content of the manuscript, and agreed upon the final submitted version. All Intellectual Property Rights arising out of the current clinical study are vest in or exclusively licensed to GW.

Abstract

Background

Peripheral neuropathic pain (PNP) associated with allodynia poses a significant clinical challenge. The efficacy of Δ9-tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray, a novel cannabinoid formulation, was investigated in this 15-week randomized, double-blind, placebo-controlled parallel group study.

Methods

In total, 303 patients with PNP associated with allodynia were screened; 128 were randomized to THC/CBD spray and 118 to placebo, in addition to their current analgesic therapy. The co-primary efficacy endpoints were the 30% responder rate in PNP 0–10 numerical rating scale (NRS) score and the mean change from baseline to the end of treatment in this score. Various key secondary measures of pain and functioning were also investigated.

Results

At the 30% responder level, there were statistically significant treatment differences in favour of THC/CBD spray in the full analysis (intention-to-treat) dataset [p = 0.034; 95% confidence interval (CI): 1.05–3.70]. There was also a reduction in mean PNP 0–10 NRS scores in both treatment groups that was numerically higher in the THC/CBD spray group, but which failed to reach statistical significance. Secondary measures of sleep quality 0–10 NRS score (p = 0.0072) and Subject Global Impression of Change (SGIC) (p = 0.023) also demonstrated statistically significant treatment differences in favour of THC/CBD spray treatment.

Conclusions

These findings demonstrate that, in a meaningful proportion of otherwise treatment-resistant patients, clinically important improvements in pain, sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray. THC/CBD spray was well tolerated and no new safety concerns were identified.

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