Δ9-tetrahydrocannabinol and the opioid receptor agonist piritramide do not act synergistically in postoperative pain

Background. it is concluded from animal experiments that cannabinoid receptor and popioid receptor agonists act synergistically with respect to anti nociception. In order to demonstrate this effect under clinical conditions, we conducted a randomized double blind trial with patients after radical prostatectomy. Patients and methods. From the evening before the operation until the morning of the second postoperative day, all patients received eight oral doses of either placebo or 5 mg Delta(9)-tetrahydrocannabinol (dronabinol). Postoperatively patients had access to patient-controlled analgesia with the p-opioid agonist piritramide for 48 h. We expected patients receiving dronabinol to require significantly less piritramide compared to patients on placebo. Results. The consumption of piritramide was recorded in 100 patients after radical retropubic prostatectomy with regional lymphadenectomy. Patients in the placebo group consumed 74 mg (median), interquartile range (IQR) 44-90 mg, patients in the verum group consumed 54 mg (median) IQR 46-88 mg. The difference between groups was not statistically significant. Plasma concentrations of Delta(9)-THC were measurable in all patients in the verum group. The levels (median) were 1.5 ng/ml (IQR 0.6-2.3),1.3 ng/ml (IQR 0.52.2) and 1.9 ng/ml (IQR 0.8-2.7) on the day of operation, the first and second postoperative day, respectively. Conclusion. We found neither a synergistic nor even an additive antinociceptive interaction between 69-tetrahydrocannabinol and the mu-opioid agonist piritramide in a setting of acute postoperative pain.