When should physicians start thinking about medical cannabis for patients?

Key takeaways:

• Cannabis may alleviate neuropathic pain, chemotherapy-induced nausea/vomiting and MS-associated spasticity.
• The studies, however, are generally of low quality, a speaker said.

BOSTON — There is some evidence that cannabinoids may help with neuropathic pain, chemotherapy-induced nausea/vomiting and MS-associated spasticity, “but it’s not exactly a slam dunk,” a speaker said.

Most of the evidence on the health effects of cannabinoids comes from trials outside the United States and often involves synthetic forms “that may or may not have any similarity to what our patients get when they go to a dispensary,” Ellie Grossman, MD, MPH, an instructor in the division of internal medicine at Harvard Medical School and Cambridge Health Alliance, said during a presentation at the ACP Internal Medicine Meeting. In addition, studies typically involve self-reports, and patients may not know how much chemical they are ingesting.

Despite these limitations, Grossman told attendees that “if you’re going to leave here with anything today, you can remember there are three indications for which there is some evidence in favor of cannabinoid effectiveness.”

‘Some signal for helpfulness’

“By far” the most common medical condition that cannabinoids are used for is chronic pain, Grossman said. It is also one of the more commonly studied medical conditions in cannabis trials, particularly neuropathic pain.

A meta-analysis from 2015 showed that cannabinoids reduced chronic pain, although “the effect size is not huge,” Grossman said.

“If you look at the size of those studies, they are all individually small [and] they are generally low-quality studies. But there is this thrust of evidence showing an effect,” she said.

There are essentially no data comparing cannabinoids with other pain agents, Grossman noted. Most of the trials are older and used pain scores as the primary outcome. Since then, researchers determined that functional outcomes are a better marker. So, there is “almost no evidence to guide us” on those clinically important outcomes, Grossman said.

“Garbage in, garbage out,” she added.

The Agency for Healthcare Research and Quality is conducting a living systematic review that is updated every quarter. The most recent review from January found that one product — a THC:CBD oromucosal spray that is not available in the U.S. — appears to have a beneficial effect on chronic pain with moderate evidence. All the other cannabis products studied either had no evidence or low-quality evidence.

A Cochrane review restricted to neuropathic pain identified 16 studies with 1,750 participants. These studies showed a moderate effect, but the quality was very low, and twice as many patients in the cannabis arms dropped out because of adverse events, Grossman said.

“There is some signal for helpfulness for cannabinoid, but it’s messy,” she said.

The two other indications with data supporting the use of cannabinoids are chemotherapy-induced nausea/vomiting and MS-associated spasticity. Like chronic pain, however, the evidence is “not great quality,” Grossman said. For chemotherapy-induced nausea/vomiting, some studies demonstrated an improvement compared with placebo, but there are no data comparing cannabinoids with other antiemetics. For spasticity, there appears to be an improvement in patient-related outcomes, but the evidence on clinician-reported outcomes is unclear, according to Grossman.

There is less robust or negative evidence of cannabinoids for:

• weight loss/anorexia in HIV;
• sleep disorders and anxiety;
• glaucoma;
• Tourette’s syndrome;
• inflammatory bowel disease; and
• PTSD.

Adverse effects

In studies of patients who used cannabinoids medicinally, Grossman said short-term adverse effects included sedation, “feeling high,” dizziness, speech disorders, muscle twitching, hypertension, numbness, psychiatric effects, euphoria, dysphoria, impaired memory and disassociation.

“There are a whole lot of questions about longer term health care risks,” she said. “All the evidence comes from studies of people who have been using it for recreational reasons.”

When inhaled or smoked, cannabinoids are associated with an increased risk for coughing, wheezing and sputum/phlegm, according to Grossman.

When used during pregnancy, there is an increased risk for lower neonatal birth weight and preterm labor.

Additionally, there is emerging evidence linking cannabis to myocardial infarction, stroke, COPD and mortality.

“The signals keep coming, in particular about cardiovascular disease,” Grossman said.

Other longer term risks of cannabinoids include the development of psychotic symptoms, psychosis relapse, suicide and cannabis use disorder. In a study published in JAMA Network Open in 2023, 13% of participants who used cannabis for medical purposes met the criteria for cannabis use disorder. Among them, 1.3% met criteria for moderate to severe cannabis use disorder.

When weighing the benefits and risks of cannabinoids, Grossman pointed attendees to a clinical practice guideline developed by Canadian researchers.

According to the guideline:

• In order to achieve a 30% or greater reduction in chronic pain, the number of patients needed to treat is 11 and the number needed to harm is six.
• To control chemotherapy-induced nausea/vomiting, the number needed to treat is three and the number needed to harm is six.
• For a 30% or greater improvement in spasticity, the number needed to treat is 10 and the number needed to harm is six.

“How we weigh that in our individual patients, I leave up to you,” Grossman said. “That is one way of thinking about this.”

References:

• Allan GM, et al. Can Fam Physician. 2018;64(2):111-120.
• Grossman E. Cannabinoids for clinical care: What prescribers need to know. Presented at: ACP Internal Medicine Meeting; April 18-20, 2024; Boston.
• Lapham GT, et al. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2023.28934.
• Living systematic reviews: Examining excluded full-text articles to better understand the evidence base on plant-based treatments for chronic pain. https://effectivehealthcare.ahrq.gov/sites/default/files/related_files/living-systematic-reviews-full-text-articles-white-paper.pdf. Published January 2024. Accessed April 22, 2024.
• Mücke M, et al. Cochrane Database Syst Rev. 2018;doi:10.1002/14651858.CD012182.pub2.
• Whiting PF, et al. JAMA. 2015;doi:10.1001/jama.2015.6358.