Medical Cannabis

Clarissa Chan, PharmD

According to CDC, people most often cite pain management as their reason for using medical cannabis in the United States. But a new clinical practice guideline published by Busse and colleagues in the September 2021 issue of BMJ concludes there is weak evidence to support the use of non-inhaled medical cannabis or cannabinoids for chronic pain. The recommendation is based on a robust analysis of results from 32 randomized controlled clinical trials.

Trial of medical cannabis?

While Busse and colleagues’ guideline does not recommend the use of medical cannabis or cannabinoids in chronic pain as the standard of care, the authors do suggest offering patients a trial of non-inhaled medical cannabis or cannabinoids if moderate to severe chronic pain standard care and management is insufficient.

“Smoking cannabis is not advised because of the adverse [pulmonary] effects of smoking,” said Edeltraut Kröger, BPharm, PhD, a research scientist at Centre d’excellence sur le vieillissement de Québec, who did not contribute to the guideline.

The guideline recommends that therapeutic trials of medical cannabis should start with low doses, gradually increasing the dose and THC level based on clinical response and tolerability.

Busse and colleagues suggest a starting dose of 5 mg cannabidiol (CBD) twice daily, increasing 10 mg every 2 to 3 days to a 40 mg maximum daily dose.

If the response is insufficient, they recommend adding 1 mg to 2.5 mg tetrahydrocannabinol (THC) per day and titrating 1 mg to 2.5 mg every 2 to 7 days for a maximum of 40 mg/day. Prior cannabis use should be taken into consideration.

“I would advise [patients] to talk to their doctor about their wish to try medical cannabis so their doctor can follow up on what they use, how often they use it, and positive or adverse effects they perceive,” said Kröger, who is also an adjunct professor at the Faculty of Pharmacy, Université Laval and the Department of Medicine, McGill University in Quebec, Canada.

Benefits vs. risks

The researchers found high-quality evidence to support the potential benefits of medical cannabis use on improved sleep quality and physical function, but the review found
moderate-quality evidence for a reduction in pain.

According to the research team, serious adverse effects are unlikely to occur in patients taking medical cannabis, with the risk of fatal overdose nearly nonexistent.

Based on the studies reviewed, the adverse effects—in order of severity—experienced by trial participants include cognitive impairment, vomiting, impaired attention, drowsiness, dizziness, nausea, and diarrhea. The most common non-serious adverse effect was dizziness.

Special populations

Since THC, the psychoactive component of medical cannabis that produces a “high” sensation, may cause severe adverse effects in the neurocognitive development of younger or adolescent patients, the researchers recommend the use of CBD-predominant preparations in this population. Their review also excluded people with concurrent mental illness. When starting or changing doses of medical cannabis, the guidelines recommend that people avoid driving or operating machinery. In patients who are pregnant or breastfeeding, medical cannabis is not recommended since evidence of adverse effects in studies are inconclusive.

Poorly regulated

“Medical cannabis is not standardized in the same way conventional medications are,” said Kröger. Because cannabis products available in the United States are not regulated by FDA and may vary widely in their THC and CBD composition, caution should be used when taking medicinal cannabis.

“Since doctors authorize medical cannabis use without regular and recurrent prescribing to [monitor] the dosage and length of use, providers have several difficulties with medical cannabis,” said Kröger. “This includes lack of evidence on the effectiveness and safety of medical cannabis and difficulties with dosing and follow-up.”

Because medical cannabis is not an FDA-regulated medication, it is often very challenging for researchers to obtain legal authorization for its use in experimental studies or trials, but hopefully this will change. Hundreds of scientists signed a letter against this policy in Nature Medicine’s April 2021 issue.

Although pain is a very personal experience and not easy to measure accurately in trials, if small improvements in pain, physical functioning, and sleep quality are worth low-to-modest risks of short-term harm, then encouraging the trial of non-inhaled medical cannabis or cannabinoids in addition to standard-of-care pain management may be worth exploring.