Cannabinoids for Postoperative Pain

To the Editor:—An article published by Holdcroft et al. in the May 2006 issue of ANESTHESIOLOGY reported the analgesic and adverse effects of an oral cannabis extract for postoperative pain management. To date, only three other manuscripts investigating the role of cannabinoids in postoperative pain have been published. The conclusions from these studies are that cannabinoids are not ideally suited to manage postoperative pain, being either moderately effective, not different from placebo, or even antianalgesic at high doses. However, a definitive conclusion of the role of cannabinoids in the postoperative setting cannot yet be made because only 202 patients were studied using different drugs, dosages, routes of administration, and protocols. In their study, Holdcroft et al. used an escalating-dose technique, which leads to two main problems: the lack of blinding and the absence of a placebo group. Furthermore, Holdcroft et al. stated, “The study recruited all types of surgical patients” and “Apart from the different distribution of surgical types, the three dose groups were similar at baseline.” This obviously introduces a major problem in the interpretation of their results. Another potential problem with the study by Holdcroft et al. is that the 65 patients enrolled in their study were recruited from eight different centers, which does not help to obtain consistent data. The actual design of the study could also be criticized because patients were only studied for a 6-h period (periods longer than 6 h are advocated) and, more importantly, because the study drug was administered only when clinical evidence showed that patient-controlled analgesia morphine was not necessary anymore. Therefore, the first hours (or days?) immediately following the operation were not studied. The authors do not report the time when patients were in fact recruited and when they were given the cannabis extracts. This information is crucial to understanding when the study took place. Furthermore, in real life, using the so-called multimodal analgesia approach, patients should receive adjuvant analgesics (acetaminophen, nonsteroidal antiinflammatory drugs) at the beginning of the postoperative period and not after morphine administration has been stopped. Finally, pain on movement was measured, but no details were given on how these assessments were made considering the many types of surgery performed. A last comment is on the choice of Cannador (IKF, Berlin, Germany) as the cannabinoid of choice for this study. Although it contains tetrahydrocannabinol, its association with cannabidiol and other cannabis extracts (which ones and in what proportions?) is certainly another variable that potentially complicates the interpretation of the results. Despite these limitations, the authors must be congratulated because this research area is not easy: there are difficulties in funding such trials, an unfavorable political climate, and societal and institutional concerns related to the use of cannabinoids. It is reasonable to question why there has been so little research conducted in this area, and it is possible that obstacles to the conduct of such research continue to exist.