—By Naveed Saleh, MD, MS

The recreational use of marijuana is currently legal in 11 states—Alaska, California, Colorado, Illinois, Maine, Massachusetts, Michigan, Nevada, Oregon, Vermont and Washington—and also in Washington, D.C. Several other states allow marijuana use for medicinal reasons. State legislative changes that have legalized marijuana have brought both medical opportunities and challenges. One challenge involves understanding the effect of cannabis on procedural anesthesia.

In a retrospective study published in the Journal of the American Osteopathic Association (2019; 119:307-311), investigators examined whether patients who regularly used cannabis required more anesthesia during endoscopy, and found that perhaps unsurprisingly, they did.

“The research does not suggest that people should not use cannabis,” said Mark A. Twardowski, DO, with Western Medical Associates in Grand Junction, Colo. “It just suggests that the use is not without consequences. One consequence is that more medications may be required for procedures. This increased dose may put people at a higher risk for respiratory suppression during endoscopic procedures.”


Propofol Requirements Doubled

In this single-center study, 250 medical records were reviewed from a single endoscopist practicing in Colorado, to minimize variability in sedation technique. The researchers investigated whether there was variation in relative amounts of sedation medication required in cannabis users versus nonusers. In Colorado, recreational cannabis use was legalized in 2012.


For sedation, cannabis users needed an average of 125.93 mcg of fentanyl, 9.15 mg of midazolam, and 44.81 mg of propofol, compared with nonusers who needed 109.91 mcg of fentanyl, 7.61 mg of midazolam, and 13.83 mg of propofol. The differences translated to an additional 14% of fentanyl, an additional 19.6% of midazolam, and a whopping 220.5% more propofol during endoscopy needed by cannabis users.


Dr. Twardowski, an internist who performs endoscopies, hypothesized that marijuana could increase anesthesia requirements based on anecdotal observation. “The information has galvanized what we thought we were seeing as a trend [in practice],” he said.

The findings have already influenced how Dr. Twardowski and his colleagues screen patients. “We are being careful to obtain cannabis use status from our patients and to recognize that we may need to use more medications in that population who regularly uses cannabis,” he said. Specifically, a nursing preprocedure question about cannabis use was added to patient intake forms in January 2015.

Looking forward, Dr. Twardowski said, “The next step for my team is to further investigate the relationships in a broader array of perioperative sedation, anesthetic and pain control medications to see if we can find any useful trends that may help guide future clinical practice. We will begin to evaluate the effects on a broader group of anesthetic agents in the next phase of the study.”


It remains unclear what effect regular cannabis use has on the need for opioids and other pain medications. “We do not know if regular users require higher doses of pain medications. This has not been well studied. We will begin to look at some of these issues in phase 2 of our study,” Dr. Twardowski said.

Response bias did not appear to be a limitation of the study. “We find that patients are generally honest about their use status since it is legal in Colorado. They are even more likely to be honest when they discover the information may have an effect on their medical care,” Dr. Twardowski said.

Up-to-date research indicates that the half-life of tetrahydrocannabinol (THC), the main active component of cannabis, is five to 13 days, with total excretion taking up to 25 days.


As for the mechanism underlying the effect of cannabis on anesthesia, experts hypothesize that THC may interact with specific cannabinoid receptors, potentially including opioid and benzodiazepine receptors. Consequently, the interaction of opioids or benzodiazepines with these receptors in patients who regularly use cannabis could be disrupted.

Historically, it has been difficult to study the effects of marijuana on dose requirements for sedatives because it is classified as a Schedule I drug by the Drug Enforcement Administration. A 2009 study, done in Australia, analyzed the induction dose of propofol necessary in patients using cannabis in 30 users versus 30 nonusers. The investigators concluded that cannabis use increased the need for propofol during anesthesia when employing a laryngeal mask.

Dr. Twardowski commented on the results of the study. “My medical opinion about cannabis is that it is a reality that we have to deal with. I am neither pro nor con, but I am frustrated—as everyone in health care should be—that a substance has been legalized for general consumption with almost no meaningful evaluation of its true medical effects, drug interactions, etc. The substance was demonized and therefore not able to be studied, then it was legalized without appropriate research.”

Dr. Twardowski reported no relevant financial disclosures.