We thank Pierre Beaulieu for his interest in our study of cannabinoids for postoperative pain. However, we cannot concur with his view that cannabinoids are only moderately effective analgesics. We found that, across different surgeries and institutions, pain relief equivalent to the best available postoperative analgesia was achieved. We agree that results from one type of cannabinoid may not be comparable to those from another type and that larger studies are needed. However, we found that our stringent entry criteria, intended to exclude patients with serious medical conditions, made it essential to recruit from a large number of centers.

Our study was designed to measure the effectiveness of cannabinoids alone without the advantage of other analgesic combinations, as occurs in clinical practice.1Hence, the time to escape analgesia was an important outcome. In comparison with the study of Beaulieu,2in which the outcome measure was morphine consumption, we can be sure that the effects we measured were from cannabinoids, not the result of synergistic effects from an opioid-cannabinoid combination, as has been described in preclinical studies.3Our aim was to investigate whether cannabinoids were analgesic when administered as the sole agent and to find their most effective dose; our results provide confirmatory evidence for analgesia at the higher doses we used.

Interestingly, the duration of our study was determined in pretrial workshops by the same authors that Beaulieu cites as advocating durations longer than 6 h. The rationale was that this was the first time that cannabinoids had been used postoperatively, in fasting patients, and a single-dose study was safest; furthermore, a 24-h study would have required waking the patient at night to obtain regular pain scores, which might have made recruitment even less attractive. In retrospect, the times to rescue analgesia also support this view. Because total pain relief and pain intensity differences summary measures carry forward the final value before rescue analgesia, sensitivity would be lost if assessments continued until all patients requested escape analgesia. In addition, the use of an oral preparation precluded early administration after major surgery, and the single dose was delivered to most patients within 24 h of surgery. This regimen was similar to that used clinically in the study centers for orally administered analgesics.

Beaulieu asks how pain on movement was measured. The protocol for the study standardized these movements for each type of surgery to establish conformity across sites; our method was comparable to his. He also requests justification for and content of Cannador (IKF, Berlin, Germany). Most of these details are in the article. In addition, the study was conducted in parallel with the CAMS study4because postoperative pain and multiple sclerosis were both considered to be important areas to investigate the medicinal uses of cannabis.

*Imperial College London and Chelsea and Westminster Hospital, London, United Kingdom. a.holdcroft@imperial.ac.uk

Holdcroft A, Maze M, Doré C, Tebbs S, Thompson S: A multicentre dose-escalating study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain. Anesthesiology 2006; 104:1040–6
Beaulieu P: Effects of nabilone, a synthetic cannabinoid, on postoperative pain. Can J Anesth 2006; 53:769–75
Cichewicz DL, McCarthy EA: Antinociceptive synergy between Δ9-tetrahydrocannbinol and opioids after oral administration. J Pharmcol Exp Ther 2003; 304:1010–5
Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A on behalf of the UKMS Research Group: Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): Multicentre randomised placebo-controlled trial. Lancet 2003;362:1517–26.
on behalf of the UKMS Research Group