[Delta(9)-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 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.


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.


CONCLUSIONS
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.
Seeling
W
W
Klinik für Anästhesiologie, Universitätsklinikum Ulm, Germany. erika.stiepan@medizin.uni-ulm.de
Kneer
L
L
Büchele
B
B
Gschwend
J E
JE
Maier
L
L
Nett
C
C
Simmet
T
T
Steffen
P
P
Schneider
M
M
Rockemann
M
M
D000368:Aged; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D001143:Arousal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008197:Lymph Node Excision; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D010892:Pirinitramide / Q000008:administration & dosage / Q000627:therapeutic use*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000601:surgery; D017450:Receptors, Opioid, mu / Q000819:agonists; D015656:Respiratory Mechanics / Q000187:drug effects
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D010892:Pirinitramide; D013759:Dronabinol