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
Open accessAbstract
This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. In total, 177 patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, entered a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Patients were randomized to THC:CBD extract (n = 60), THC extract (n = 58), or placebo (n = 59). The primary analysis of change from baseline in mean pain Numerical Rating Scale (NRS) score was statistically significantly in favor of THC:CBD compared with placebo (improvement of -1.37 vs. -0.69), whereas the THC group showed a nonsignificant change (-1.01 vs. -0.69). Twice as many patients taking THC:CBD showed a reduction of more than 30% from baseline pain NRS score when compared with placebo (23 [43%] vs. 12 [21%]). The associated odds ratio was statistically significant, whereas the number of THC group responders was similar to placebo (12 [23%] vs. 12 [21%]) and did not reach statistical significance. There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups. No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment. However, the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Questionnaire showed a worsening in nausea and vomiting with THC:CBD compared with placebo (P = 0.02), whereas THC had no difference (P = 1.0). Most drug-related adverse events were mild/moderate in severity. This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Two controlled studies found no effect of cannabinoids on opioid dose requirements.
“Two controlled studies found no effect of cannabinoids on opioid dose requirements (Johnson et al, 2010;Seeling et al, 2006).”
From Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis (2017) · cites this paper as Johnson et al, 2010
In Johnson 2010, there was no change in median amount of breakthrough opioid medication in any group; change in pain NRS from baseline was statistically significantly in favor of delta-9-THC:CBD compared with placebo.
“No change in median amount of breakthrough opioid medication in any group Change in pain NRS (out of 10) from baseline was statistically significantly in favor of delta-9-THC:CBD compared with the placebo”
From Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis (2017) · cites this paper as Johnson 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Aaronson, N. K., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N. J., Filiberti, A., Flechtner, H., Fleishman, S. B., Haes, J. C. J. M. D., et al. (1993) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/85.5.365 · Cited by 16,005 · see citing works
Farrar, J. T., Young, J. P., LaMoreaux, L., Werth, J. L., & Poole, M. R. (2001) · Pain · doi:10.1016/s0304-3959(01)00349-9 · Cited by 5,808 · see citing works
A sharper Bonferroni procedure for multiple tests of significance
HOCHBERG, Y. (1988) · Biometrika · doi:10.1093/biomet/75.4.800 · Cited by 4,829 · see citing works
Scottish Intercollegiate Guidelines Network
Twaddle, S., & Qureshi, S. (2005) · Evidence-based Healthcare and Public Health · doi:10.1016/j.ehbc.2005.09.008 · Cited by 4,079 · see citing works
Core outcome measures for chronic pain clinical trials: IMMPACT recommendations
Dworkin, R. H., Turk, D. C., Farrar, J. T., Haythornthwaite, J. A., Jensen, M. P., Katz, N. P., Kerns, R. D., Stucki, G., Allen, R. R., Bellamy, N., et al. (2005) · Pain · doi:10.1016/j.pain.2004.09.012 · Cited by 3,732 · see citing works
Core outcome domains for chronic pain clinical trials: IMMPACT recommendations
Turk, D. C., Dworkin, R. H., Allen, R. R., Bellamy, N., Brandenburg, N., Carr, D. B., Cleeland, C., Dionne, R., Farrar, J. T., Galer, B. S., et al. (2003) · Pain · doi:10.1016/j.pain.2003.08.001 · Cited by 3,510 · see citing works
Clinical applications of visual analogue scales: a critical review
McCormack, H. M., Horne, D. J. D. L., & Sheather, S. J. (1988) · Psychological Medicine · doi:10.1017/s0033291700009934 · Cited by 2,108 · see citing works
Pain and Its Treatment in Outpatients with Metastatic Cancer
Cleeland, C. S., Gonin, R., Hatfield, A. K., Edmonson, J. H., Blum, R. H., Stewart, J. A., & Pandya, K. J. (1994) · New England Journal of Medicine · doi:10.1056/nejm199403033300902 · Cited by 2,019 · see citing works
Pertwee, R. G. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707442 · Cited by 1,953 · see citing works
Oxford Textbook of Palliative Medicine
(2009) · Oxford University Press eBooks · doi:10.1093/med/9780198570295.001.0001 · Cited by 1,921 · see citing works
Pharmacology of cannabinoid CB1 and CB2 receptors
Pertwee, R. G. (1997) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(97)82001-3 · Cited by 1,489 · see citing works
Bonica, J. J. (1954) · The American Journal of the Medical Sciences · doi:10.1097/00000441-195405000-00015 · Cited by 1,467 · see citing works
Bisogno, T., Hanuš, L., PETROCELLIS, L. D., Tchilibon, S., Ponde, D. E., Brandi, I., Moriello, A. S., Davis, J. B., Mechoulam, R., & Marzo, V. D. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704327 · Cited by 1,315 · see citing works
Estimates of Location Based on Rank Tests
Hodges, J. L., & Lehmann, E. L. (1963) · The Annals of Mathematical Statistics · doi:10.1214/aoms/1177704172 · Cited by 1,276 · see citing works
Universities and tobacco money
Cohen, J. E. (2001) · BMJ · doi:10.1136/bmj.323.7303.1 · Cited by 942 · see citing works
Cannabidiol and (−)Δ <sup>9</sup> -tetrahydrocannabinol are neuroprotective antioxidants
Hampson, A. J., Grimaldi, M., Axelrod, J., & Wink, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.8268 · Cited by 850 · see citing works
Cannabinoid pharmacology: the first 66 years
Pertwee, R. G. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706406 · Cited by 783 · see citing works
Thomas, A., Baillie, G. L., Phillips, A. M., Razdan, R. K., Ross, R. A., & Pertwee, R. G. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707133 · Cited by 763 · see citing works
Cannabinoid receptors and pain
Pertwee, R. G. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00031-9 · Cited by 741 · see citing works
Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis
Rog, D. J., Nurmikko, T. J., Friede, T., & Young, C. A. (2005) · Neurology · doi:10.1212/01.wnl.0000176753.45410.8b · Cited by 679 · see citing works
Malfait, A. M., Gallily, R., Sumariwalla, P. F., Malik, A. S., Andreakos, E., Mechoulam, R., & Feldmann, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.160105897 · Cited by 669 · see citing works
Russo, E. B., & Guy, G. W. (2005) · Medical Hypotheses · doi:10.1016/j.mehy.2005.08.026 · Cited by 608 · see citing works
Wade, D. T., Makela, P., Robson, P., House, H., & Bateman, C. (2004) · Multiple Sclerosis Journal · doi:10.1191/1352458504ms1082oa · Cited by 589 · see citing works
Carrier, E. J., Auchampach, J. A., & Hillard, C. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511232103 · Cited by 497 · see citing works
Analysis of Covariance Using the Rank Transformation
Conover, W. J., & Iman, R. L. (1982) · Biometrics · doi:10.2307/2530051 · Cited by 448 · see citing works
Pharmacological activity of the cannabinoid receptor agonist, anandamide, a brain constituent
Fride, E., & Mechoulam, R. (1993) · European Journal of Pharmacology · doi:10.1016/0014-2999(93)90468-w · Cited by 448 · see citing works
Nurmikko, T. J., Serpell, M. G., Hoggart, B., Toomey, P. J., Morlion, B. J., & Haines, D. (2007) · Pain · doi:10.1016/j.pain.2007.08.028 · Cited by 431 · see citing works
Campbell, F. A., Tramèr, M. R., Carroll, D., Reynolds, D. J. M., Moore, R. A., & McQuay, H. J. (2001) · BMJ · doi:10.1136/bmj.323.7303.13 · Cited by 422 · see citing works
Randomized controlled trial of cannabis‐based medicine in spasticity caused by multiple sclerosis
Collin, C., Davies, P., Mutiboko, I. K., Ratcliffe, S. H., & for the Sativex Spasticity in MS Study Group (2007) · European Journal of Neurology · doi:10.1111/j.1468-1331.2006.01639.x · Cited by 379 · see citing works
The analgesic properties of delta‐9‐tetrahydrocannabinol and codeine
Noyes, R., Brunk, S. F., Avery, D. H., & Canter, A. (1975) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt197518184 · Cited by 378 · see citing works
Berman, J. S., Symonds, C., & Birch, R. (2004) · Pain · doi:10.1016/j.pain.2004.09.013 · Cited by 362 · see citing works
(1999) · Journal of Pain and Symptom Management · doi:10.1016/s0885-3924(99)00110-4 · Cited by 322 · see citing works
Oxford Textbook of Palliative Medicine.
Wee, B. (2004) · Journal of the Royal Society of Medicine · doi:10.1258/jrsm.97.7.356 · Cited by 303 · see citing works
Wade, D. T., Mäkelä, P., House, H., Bateman, C., & Robson, P. (2006) · Multiple Sclerosis Journal · doi:10.1177/1352458505070618 · Cited by 285 · see citing works
Analgesic Effect of Delta‐9‐Tetrahydrocannabinol
Noyes, R., Brunk, S. F., BARAM, D. A., & Canter, A. (1975) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1975.tb02348.x · Cited by 272 · see citing works
Russo, E. B., Guy, G. W., & Robson, P. (2007) · Chemistry & Biodiversity · doi:10.1002/cbdv.200790150 · Cited by 228 · see citing works
ROG, D., NURMIKKO, T., & YOUNG, C. (2007) · Clinical Therapeutics · doi:10.1016/j.clinthera.2007.09.013 · Cited by 187 · see citing works
Barnes, M. P. (2006) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.7.5.607 · Cited by 161 · see citing works
Strategies for the Treatment of Cancer Pain in the New Millennium
Ripamonti, C. I., & Dickerson, E. D. (2001) · Drugs · doi:10.2165/00003495-200161070-00005 · Cited by 136 · see citing works
Pharmacology of Cannabinoid CB 1 and CB 2 Receptors
Pertwee, R. G. (1997) · Pharmacology & Therapeutics · Cited by 112 · see citing works
Multidimensional measurement of cancer pain: Comparisons of US and Vietnamese patients
Cleeland, C. S., Ladinsky, J. L., Serlin, R. C., & Thuy, N. C. (1988) · Journal of Pain and Symptom Management · doi:10.1016/0885-3924(88)90134-0 · Cited by 92 · see citing works
Effect of a nitrogen analog of tetrahydrocannabinol on cancer pain
Staquet, M. J., Gantt, C., & Machin, D. (1978) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt1978234397 · Cited by 87 · see citing works
Neuropharmacology and therapeutic potential of cannabinoids
Pertwee, R. G. (2000) · Addiction Biology · doi:10.1080/13556210071252 · Cited by 85 · see citing works
Synergy between Δ9-tetrahydrocannabinol and morphine in the arthritic rat
Cox, M. L., Haller, V. L., & Welch, S. P. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.04.010 · Cited by 78 · see citing works
Effect of benzopyranoperidine, a Δ‐9‐THC congener, on pain
Jochimsen, P. R., Lawton, R. L., VerSteeg, K., et al. (1978) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt1978242223 · Cited by 51 · see citing works
(2009) · Oxford University Press eBooks · doi:10.1093/med/9780199236640.001.0001 · Cited by 35 · see citing works
Clinical Pain Management: Cancer Pain
Edwards, N. D. (2003) · British Journal of Anaesthesia · doi:10.1093/bja/aeg533 · Cited by 21 · see citing works
Silberberg, D. H., & Thompson, A. J. (2004) · Multiple Sclerosis Journal · doi:10.1191/1352458504ms1003ed · Cited by 20 · see citing works
Choice of Opioids and the WHO Ladder
Glare, P. A. (2011) · Journal of Pediatric Hematology/Oncology · doi:10.1097/mph.0b013e3182121a2b · Cited by 19 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [7]7. Noyes R, Brunk SF, Avery DA, et al. The analge- sic properties of delta 9-tetrahydro-cannabinol and codeine. Clin Pharmacol Ther 1975;18:84e89.
- [42]42. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: D9-tetrahydrocannabinol, cannabidiol and D9-tetra- hydrocannabivarin. Br J Pharmacol 2008;153: 199e215.
Cited by
Sorted by citations
Cannabinoids for Medical Use: A Systematic Review and Meta-analysis
Whiting, P. F., Wolff, R. F., Deshpande, S., Di Nisio, M., Duffy, S., Hernandez, A. V., Keurentjes, J. C., Lang, S., Misso, K., Ryder, S., et al. (2015) · JAMA · doi:10.1001/jama.2015.6358 · Cited by 2,169 · see citing works
Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines
Fallon, M., Giusti, R., Aielli, F., Hoskin, P., Rolke, R., Sharma, M., & Ripamonti, C. I. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy152 · Cited by 954 · see citing works
Self-citationPractical considerations in medical cannabis administration and dosing
MacCallum, C. A., & Russo, E. B. (2018) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2018.01.004 · Cited by 663 · see citing works
Portenoy, R. K., Ganae-Motan, E. D., Allende, S., Yanagihara, R., Shaiova, L., Weinstein, S., McQuade, R., Wright, S., & Fallon, M. T. (2012) · The Journal of Pain · doi:10.1016/j.jpain.2012.01.003 · Cited by 420 · see citing works
Self-citationNugent, S. M., Morasco, B. J., O'Neil, M. E., Freeman, M., Low, A., Kondo, K., Elven, C., Zakher, B., Motu'apuaka, M., Paynter, R., et al. (2017) · Annals of Internal Medicine · doi:10.7326/m17-0155 · Cited by 301 · see citing works
Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy
Wallace, M. S., Marcotte, T. D., Umlauf, A., Gouaux, B., & Atkinson, J. H. (2015) · The Journal of Pain · doi:10.1016/j.jpain.2015.03.008 · Cited by 276 · see citing works
Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis
Nielsen, S., Sabioni, P., Trigo, J. M., Ware, M. A., Betz-Stablein, B. D., Murnion, B., Lintzeris, N., Khor, K. E., Farrell, M., Smith, A., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.51 · Cited by 265 · see citing works
Bilbao, A., & Spanagel, R. (2022) · BMC Medicine · doi:10.1186/s12916-022-02459-1 · Cited by 181 · see citing works
Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity
Weizman, L., Dayan, L., Brill, S., Nahman-Averbuch, H., Hendler, T., Jacob, G., & Sharon, H. (2018) · Neurology · doi:10.1212/wnl.0000000000006293 · Cited by 120 · see citing works
Subjective and Physiological Effects After Controlled Sativex and Oral THC Administration
Karschner, E. L., Darwin, W. D., McMahon, R. P., Liu, F., Wright, S., Goodwin, R. S., & Huestis, M. A. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2010.318 · Cited by 117 · see citing works
Schlag, A. K., O'Sullivan, S. E., Zafar, R. R., & Nutt, D. J. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108586 · Cited by 82 · see citing works
Wilkerson, J. L., Ghosh, S., Mustafa, M., Abdullah, R. A., Niphakis, M. J., Cabrera, R., Maldonado, R. L., Cravatt, B. F., & Lichtman, A. H. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.11.015 · Cited by 78 · see citing works
Aggarwal, S. K. (2013) · The Clinical Journal of Pain · doi:10.1097/ajp.0b013e31824c5e4c · Cited by 62 · see citing works
- Authors
- Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D., Potts, R., & Fallon, M. T.
- Affiliations
- Université Libre de Bruxelles (BE)
- GW Pharmaceuticals (United Kingdom) (GB)
- Edinburgh Cancer Research (GB)
- ORCID
- Fallon, Marie T.
- Venue
- Journal of Pain and Symptom Management
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 39
- Issue
- 2
- Pages
- 167-179
- ISSN
- 0885-3924 (ISSN-L)
- OpenAlex
- W2006503897
- Cited by
- 622
- References
- 49
- Citations by year
- 2026: 17 · 2025: 37 · 2024: 53 · 2023: 48 · 2022: 78 · 2021: 69 · 2020: 52 · 2019: 47 · 2018: 54 · 2017: 33 · 2016: 34 · 2015: 24 · 2014: 20 · 2013: 16 · 2012: 16
- FWCI
- 9.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Pain and Symptom Management (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- GW Pharmaceuticals
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- tetrahydrocannabinol, cannabidiol, cancer pain, refractory pain, non-opioid analgesics, opioid-refractory pain, advanced cancer, analgesia, nausea and vomiting, adverse events, quality of life
- MeSH terms
- Adult, Aged, Cannabidiol, Dose-Response Relationship, Drug, Double-Blind Method, Drug Combinations, Female, Humans, Male, Middle Aged, Neoplasms, Intractable Pain, Pain, Intractable, Dronabinol, Endpoint Determination
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
