[(9)-tetrahydrocannabinol and the opioid receptor agonist piritramide do not act synergistically in postoperative pain.]

Author(s): Seeling W, Kneer L, Buchele B, Gschwend JE, Maier L, Nett C, Simmet T, Steffen P, Schneider M, Rockemann M

Affiliation(s): Klinik fur Anasthesiologie, Klinik fur Urologie und Kinderurologie, Institut fur Pharmakologie, Toxikologie und Naturheilkunde, Klinikumsapotheke, Universitat und Universitatsklinikum, Ulm.

Publication date & source: 2006-01-03, Anaesthesist., [Epub ahead of print]

Publication type:

BACKGROUND: It is concluded from animal experiments that cannabinoid receptor and mu-opioid receptor agonists act synergistically with respect to antinociception. 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 (9)-tetrahydrocannabinol (dronabinol). Postoperatively patients had access to patient-controlled analgesia with the mu-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 (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 0.5-2.2) 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 (9)-tetrahydrocannabinol and the mu-opioid agonist piritramide in a setting of acute postoperative pain.