The selection of patients will be done during the pre-anesthetic assessment the day before
surgery. After obtaining informed consent, eligible patients will be randomly allocated to
one of the following regimes: Cannabis oil high dose (21.6 mg THC + 20 mg CBD), Cannabis oil
low dose (10.8 mg THC + 10 mg CBD), placebo control (no premedication drugs).
Treatments will be administered in a double-dummy manner. Identical bottles of Cannabis oil
and placebo should be obtained from the manufacturer (Bazelet group). Identical prefilled
vials containing sodium Olive oil should be prepared by the hospital pharmacist. To the best
of our knowledge, no clinical studies evaluating the effects of Cannabis oil on acute pain or
in a perioperative setting have been done to date. Therefore, the investigators estimate a
Cannabis oil dose range that seems reasonable to obtain relevant clinical and a manageable
occurrence of adverse events, mainly based on the recommendations from the manufacturer, on
the available pharmacological data presented in the previous section and on the results of
other clinical trials with a similar design using comparable doses of oral THC. Nevertheless,
the first 10 patients will be randomly assigned either to the Cannabis oil low dose group or
to the placebo control group only. The investigators will proceed with the full four-group
randomization only if no serious adverse events are registered among the 10 first recruited
patients.
At the arrival to the operating room, blood samples for baseline levels of cannabinoids will
be drawn at the moment of placing the intravenous line, and the first anxiety assessment
should be done by the examiner/anesthetist. The study drugs will be administered at the
entrance to the O.R. or at the induction room 15 minutes before the induction of anesthesia
(i.e.:). Premedication dose should be calculated to be the equivalent of 10 mg and 20 mg oral
THC for the low and high dose groups, respectively (4, 8 puffs). At the same time, the
prefilled drops containing Olive oil will be administered as intravenous bolus. The patients
will be immediately connected to the standard O.R. monitoring.
Induction of general anaesthesia will be done in a standardized fashion with fentanyl 2
µg/Kg, propofol 1-4 mg/Kg (and vecuronium 0.1 mg/Kg if intubation is required). For
anaesthetic maintenance, isoflurane 0.7-2% on 1:2 oxygen : nitrous oxide gas mixture, and
fentanyl boluses 1 µg/Kg to keep a bispectral index (BIS) between 40 to 60, and a heart rate
and mean arterial pressure between 70-130% from pre-induction baselines. Preemptive
antiemetics (e.g.: granisetron, ondansetron, metoclopramide, dexamethasone, etc.) should not
be given. No additional analgesics should be administered (e.g.: ketorolac or other NSAID's,
dipyrone).
A loading dose of morphine 0.2 mg/Kg will be given before the end of surgery provided that
the patient can maintain spontaneous breathing or pressure support ventilation. Intravenous
morphine patient-controlled analgesia (PCA) will be initiated on the arrival to the recovery
room with boluses of 1 mg and a lockout time of 6 minutes, without background.