A randomized, controlled study to investigate the analgesic efficacy of single doses of the cannabinoid receptor-2 agonist GW842166, ibuprofen or placebo in patients with acute pain following third molar tooth extraction

Clin J Pain. 2011 Oct;27(8):668-76. doi: 10.1097/AJP.0b013e318219799a.


Objectives: To evaluate the postoperative analgesic efficacy of GW842166, a noncannabinoid CB2 agonist, in patients undergoing third molar tooth extraction.

Methods: This randomized, double-blind, placebo-controlled study compared the analgesic efficacy of single doses of GW842166 (100 or 800 mg) or ibuprofen with placebo in patients undergoing extraction of at least 1 fully or partially impacted third molar tooth. Eligible participants were dosed preoperatively within 1 hour of surgery. Participants allocated to active comparator received a second dose of ibuprofen (400 mg), 4 hours after the first 800 mg dose. Participants in the GW842166 and placebo groups received placebo at 4 hours. Procedures for the assessment of efficacy included a visual analog scale and verbal rating scale for scoring pain up to 10 hours postsurgery, duration of analgesia, patient global evaluation, proportion of patients requiring rescue medication, and elapsed time to rescue analgesia. Analysis of covariance was used to compare efficacy variables. Patient global evaluation was analyzed using Wilcoxon rank-sum tests and time to data was analyzed using the log-rank test.

Results: Ibuprofen was significantly more effective than placebo across all endpoints. Trends for an improvement in pain scores for GW842166 800 mg failed to be of either clinical or statistical significance. GW842166 100 mg showed little separation from placebo. There was no evidence for any beneficial adjunctive effect after coadministration of rescue analgesia with GW842166. All treatments were well tolerated.

Discussion: In comparison to ibuprofen, single doses of GW842166 (100 and 800 mg) failed to demonstrate clinically meaningful analgesia in the setting of acute dental pain.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Analgesics, Non-Narcotic / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Ibuprofen / therapeutic use*
  • Male
  • Middle Aged
  • Molar, Third / surgery
  • Pain Measurement
  • Pain, Postoperative / drug therapy*
  • Pain, Postoperative / etiology
  • Pyrans / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Receptor, Cannabinoid, CB2 / agonists*
  • Retrospective Studies
  • Tooth Extraction / adverse effects*
  • Treatment Outcome
  • Young Adult


  • 2-((2,4-dichlorphenyl)amino)-N-((tetrahydro-2H-pyran-4-yl)methyl)-4-(trifluoromethyl)-5-pyrimidinecarboxamide
  • Analgesics, Non-Narcotic
  • Pyrans
  • Pyrimidines
  • Receptor, Cannabinoid, CB2
  • Ibuprofen