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

Anaesthesist. 2006 Apr;55(4):391-400. doi: 10.1007/s00101-005-0963-6.
[Article in German]


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 Delta(9)-tetrahydrocannabinol (dronabinol). Postoperatively patients had access to patient-controlled analgesia with the micro-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 0.5-2.2) 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 Delta(9)-tetrahydrocannabinol and the micro-opioid agonist piritramide in a setting of acute postoperative pain.

Publication types

  • English Abstract
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Analgesia, Patient-Controlled
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use*
  • Arousal / drug effects
  • Body Temperature / drug effects
  • Double-Blind Method
  • Dronabinol / administration & dosage
  • Dronabinol / pharmacokinetics
  • Dronabinol / therapeutic use*
  • Drug Interactions
  • Hemodynamics / drug effects
  • Humans
  • Lymph Node Excision
  • Male
  • Pain Measurement / drug effects
  • Pain, Postoperative / drug therapy*
  • Pirinitramide / administration & dosage
  • Pirinitramide / therapeutic use*
  • Prostatectomy
  • Prostatic Neoplasms / surgery
  • Receptors, Opioid, mu / agonists
  • Respiratory Mechanics / drug effects


  • Analgesics, Opioid
  • Receptors, Opioid, mu
  • Pirinitramide
  • Dronabinol