Harefuah. 2018 Mar;157(3):162-166.
[Article in Hebrew]


Background: Cannabis is the most widely used illicit drug in the world, used by approximately 2.7-4.9% of the world's population, and 7.6-10.2% of Israel's adults. During the past few years, legal systems around the world have enacted large scale adoption of the legalization of both medical and recreational cannabis. Anesthetists should therefore be prepared to treat patients who used cannabis and are undergoing elective or emergency operations. However, the interactions between cannabinoids and general anesthetic agents and the possible implications for patient care are not yet fully understood.

Objectives: The study aimed to examine how preoperative use of cannabis affects the anesthesia process, and whether this use requires special attention by the anesthesiologists during surgery. Hence, we examined the effect of preoperative administration of cannabis extract Sativex (nabiximols) on obtained BIS value relative to the concentration of anesthetic gases.

Methods: This study is a double-blind randomized controlled trial. Twenty-seven patients undergoing elective orthopedic surgery under general anesthesia were randomly allocated to one of the following regimes: high dose cannabis (6), low dose cannabis (8), active placebo (6) and placebo (7). The study drugs were administered as premedication 20 minutes before induction of general anesthesia in a double-blind fashion. Cannabis was administered in the form of nabiximols (Sativex®), which is a highly-standardized extract of cannabis plants containing known drug dosages. During the surgery, hemodynamic parameters were monitored, and the anesthesia depth was measured using a BIS monitor, which is based on brain activity analysis.

Results: We found a significant effect of treatment groups on bispectral index (BIS) after controlling for minimum alveolar concentration (MAC). The average BIS values, as measured during steady state anesthesia, were significantly higher in the high dose cannabis treatment group.

Conclusions: This study provides the first evidence that cannabinoids may affect the BIS. We speculate that the cannabinoid-induced increase in BIS may be the result of changes in EEG activity rather than an indication of a shallower anesthetic state. However, this hypothesis should be examined in further studies. The clinical importance of this study is that with patients who use cannabis adjacent to general anesthesia induction, one cannot rely on the BIS monitoring for the purpose of determining the patient sedative state.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Anesthetics, Inhalation*
  • Cannabis / chemistry*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Humans
  • Israel
  • Patient Safety
  • Plant Extracts / pharmacology*
  • Preoperative Period


  • Anesthetics, Inhalation
  • Plant Extracts