Journal of Pain and Symptom Management
Volume 39, Issue 2 , Pages 167-179 , February 2010

Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of the Efficacy, Safety, and Tolerability of THC:CBD Extract and THC Extract in Patients with Intractable Cancer-Related Pain

  • Jeremy R. Johnson, MB ChB

      Affiliations

    • Severn Hospice, Shrewsbury, Shropshire, United Kingdom
    • ,
  • Mary Burnell-Nugent, MB BChir

      Affiliations

    • St. Luke's Hospice, Turnchapel, Plymouth, United Kingdom
    • ,
  • Dominique Lossignol, MB ChB, MRCG, DRCOG

      Affiliations

    • Association Hospitaliere De Brussels, Centre des Tumeurs de l'ULB, Brussels, Belgium
    • ,
  • Elena Doina Ganae-Motan, MD

      Affiliations

    • Emergency Department, Hospital “Sf. Ioan cel Nou,” Suceava, Romania
    • ,
  • Richard Potts, BSc (Hons), MICR

      Affiliations

    • GW Pharma Ltd. , Ely, Cambridgeshire
    • ,
  • Marie T. Fallon, MB ChB, MD, FRCP (E), FRCP (Glasg)

      Affiliations

    • Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom
    • Corresponding Author InformationAddress correspondence to: Marie T. Fallon, MD, St. Columba’s Hospice Chair of Palliative Medicine, Edinburgh Cancer Research Centre, Crewe Road, Edinburgh EH4 2XR, United Kingdom.

,Accepted 22 June 2009.

References 

  1. Glare P. Choice of opioids and the WHO ladder. In:  Davis M,  Glare P,  Hardy J editor. Opioids in cancer pain. Oxford, UK: Oxford University Press; 2005;p. 221–234
  2. Scottish Intercollegiate Guidelines Network. Control of pain in patients with cancer: A National Clinical Guideline. Edinburgh, Scotland: SIGN 44; 2000;1–79
  3. Cleeland CS, Gonin R, Hatfield AK, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med. 1994;330:592–596
  4. House of Lords Select Committee on Science and Technology. Cannabis: The scientific and medical evidence, 9th Report. Session 1997–98. London, UK: House of Lords; 1998;Available from http://www.parliament.the-stationery-office.co.uk/pa/ld199798/ldselect/ldsctech/151/15101.htmAccessed January 4, 2008
  5. GW, Pharma Ltd. Product monograph: Sativex®, Ottawa, Canada. Health Canada; 2007;Available from http://cpe0013211b4c6d-cm0014e88ee7a4.cpe.net.cable.rogers.com/dpdonline/searchRequest.doAccessed March 4, 2008
  6. Noyes R, Brunk SF, Baram DA, et al. Analgesic effect of delta 9-tetrahydrocannabinol. J Clin Pharmacol. 1975;15:139–143
  7. Noyes R, Brunk SF, Avery DA, et al. The analgesic properties of delta 9-tetrahydro-cannabinol and codeine. Clin Pharmacol Ther. 1975;18:84–89
  8. Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther. 1997;74:129–180
  9. Pertwee RG. Neuropharmacology and therapeutic potential of cannabinoids. Addict Biol. 2000;5:37–46
  10. Russo EB, Guy GW. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabinol. Med Hypotheses. 2006;66:234–246
  11. Fride E, Mechoulam R. Pharmacological activity of the cannabinoid receptor agonist, anandamide, a brain constituent. Eur J Pharmacol. 1993;231:313–314
  12. Thomas A, Baillie GL, Phillips AM, et al. Cannabidiol displays unexpectedly high potency as an antagonist of CB(1) and CB(2) receptor agonists in vitro. Br J Pharmacol. 2007;150:613–623
  13. Malfait AM, Gallily R, Sumariwalla PF, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA. 2000;97:9561–9566
  14. Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and (-)delta 9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA. 1998;95:8268–8273
  15. Bisogno T, Hanus L, De Petrocellis L, et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001;134:845–852
  16. Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci USA. 2006;103:7895–7900
  17. Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol. 2006;147(Suppl 1):163–171
  18. Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol. 2001;63:569–611
  19. Campbell FA, Tamer MR, Carroll D, et al. Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systemic review. BMJ. 2001;323:1–6
  20. Jochimsen PR, Lawton RL, VerSteeg K, Noyes R. Effect of benzopyranoperidine, a delta-9 THC congener, on pain. Clin Pharmacol Ther. 1978;24(2):223–227
  21. Staquet M, Gantt C, Machin D. Effect of a nitrogen analog of tetrahydrocannabinol on cancer pain. Clin Pharmacol Ther. 1978;23(4):297–401
  22. McCormack HM, Horne DJ, Sheather S. Clinical applications of visual analogue scales: a critical review. Psychol Med. 1988;18:1007–1019
  23. Farrar JT, Young JP, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94:149–158
  24. Cleeland CS, Ladinsky JL, Serlin RC, et al. Multidimensional measurement of cancer pain: comparisons of US and Vietnamese patients. J Pain Symptom Manage. 1988;3:23–27
  25. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organisation for Research and Treatment of Cancer QLQ-C30: a quality if life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–376
  26. Rog DJ, Nurmikko TJ, Friede T, et al. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 2005;65:812–819
  27. Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004;112:299–306
  28. Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika. 1988;75:800–802
  29. Conover WJ, Inam RL. Analysis of covariance using the rank transformation. Biometrics. 1982;38:715–724
  30. Hodges JL, Lehmann EL. Estimates of location based on rank tests. Ann Math Statist. 1963;34:598–611
  31. Johnson JR, Wright ST. Cannabis-based medicines on the treatment of cancer pain: a randomised, double blind, parallel group, placebo controlled, comparative study of the efficiency, safety, and tolerability of Sativex and Tetranabinex in patients with cancer-related pain. J Support Oncol. 2005;3(Suppl 3):21
  32. Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113:9–19
  33. Collin C, Davies P, Mutiboko I, et al. Randomised controlled trial of cannabis based medicine in spasticity caused by multiple sclerosis. Eur J Neurol. 2007;14:290–296
  34. Wade DT, Makela P, Robson P, et al. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler. 2004;10:1–8
  35. Wade DT, Makela PM, House H, et al. Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Mult Scler. 2006;12:639–645
  36. Barnes MP. Sativex® clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expert Opin Pharmacother. 2006;7:607–615
  37. Nurmikko TJ, Serpell MG, Hoggart B, et al. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007;133:210–220
  38. Rog D, Nurmikko TJ, Young CA. Oromucosal delta-9-tetrahrdrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin Ther. 2007;20:2068–2079
  39. Ripamonti C, Dickerson ED. Strategies for the treatment of cancer pain in the new millennium. Drugs. 2001;61:955–977
  40. Russo E, Guy G, Robson P. Cannabis, pain and sleep: lessons from therapeutic clinical trials of Sativex cannabis based medicine. Chem Biodivers. 2007;4:1729–1743
  41. Cox ML, Haller VL, Welch SP. Synergy between delta 9-tetrahydrocannabinol and morphine in the arthritic rat. Eur J Pharmacol. 2007;12:125–130
  42. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: D9-tetrahydrocannabinol, cannabidiol and D9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153:199–215
  43. In:  Twycross R,  Wilcock A,  Charlesworth S, et al. editor. Palliative care formulary. 2nd ed. Oxford, UK: Radcliffe Publishing; 2002;
  44. Fallon M. Opioid switching and rotation. In:  Sykes N,  Fallon MT,  Patt RB editor. Clinical pain management: Cancer pain. London, UK: Hodder Arnold; 2003;p. 157–165
  45. Hanks G, Cherney N, Fallon M. The management of pain. In:  Doyle D,  Hanks G,  Cherny N,  Calman K editor. Oxford textbook of palliative medicine. 3rd ed. Oxford, UK: Oxford University Press; 2005;

 This study was sponsored by GW Pharma Ltd. All study medication was supplied by GW Pharma Ltd., and it also funded all sites involved in the study by means of per-patient payments based on recruitment. GW Pharma Ltd. has funded J. R. Johnson (primary author) to attend two conferences to present the results of this study.

PII: S0885-3924(09)00787-8

doi: 10.1016/j.jpainsymman.2009.06.008

Journal of Pain and Symptom Management
Volume 39, Issue 2 , Pages 167-179 , February 2010

Article Tools

* Image Usage & Resolution