SAN DIEGO – Despite the popularity of medical marijuana, robust evidence for its use is limited or nonexistent for most medical conditions.

“This is a tough subject to study,” Ellie Grossman, MD, said at the annual meeting of the American College of Physicians. “There is federal money that can only be used in very limited ways to study it. Our science is way behind the times in terms of what our patients are doing and using.”

Typical limitations of marijuana studies include self-report of quantity/duration used and the fact that biochemical/quantifiable measures are lacking. “For inhaled marijuana, there is variability in how much is inhaled and how deeply it’s being inhaled,” said Dr. Grossman, an internist who practices in Somerville, Mass.

Then there’s the issue of recall bias and the question as to whether oral cannabinoids equate to the plant-derived forms of medical marijuana that patients obtain from their local dispensaries.

That matters, because the majority of published studies on the topic have evaluated oral cannabinoids, not the plant form. “So, what we’re studying is vastly different from what our patients are using,” she said.

The most solid indication clinicians have for recommending medical marijuana is for chronic pain, and the most common condition studied has been neuropathy.

“Most evidence compares cannabinoid to placebo,” said Dr. Grossman, primary care lead for behavioral health integration at Cambridge (Mass.) Health Alliance. “There’s almost nothing out there comparing cannabinoid to any other pain-relieving agent that a patient might choose to use.

“A lot of the literature comes from oral synthesized agents,” she continued. “There’s a little bit of science about inhaled forms, but a lot of this is very different from what my patient got last week in a medical marijuana dispensary in Massachusetts.”

Results from a systematic review of 79 studies of cannabinoids for medical use in 6,462 study participants showed that, compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs. 20%; odds ratio, 3.82), reduction in pain (37% vs. 31%; OR, 1.41), a greater average reduction in numerical rating scale pain assessment (on a 0- to 10-point scale; weighted mean difference of –0.46), and average reduction in the Ashworth spasticity scale (–0.36) (JAMA 2015 Jun 23-30;313[24]:2456-73).

A separate meta-analysis of studies compared inhaled cannabis sativa to placebo for chronic painful neuropathy. The researchers found that those patients who used inhaled cannabis sativa were 3.2 times more likely to achieve a 30% or greater reduction in pain, compared with those in the placebo group (J. Pain 2015 Dec;16[12]:1221-32).

However, Dr. Grossman cautioned that the number of patients studied was fewer than 200, “so, you could argue that this is a body of knowledge where the jury is still out.”

According to a 2017 report from the National Academy of Sciences titled, “The Health Effects of Cannabis and Cannabinoids,” another area in which the knowledge base is less solid is the use of oral cannabinoids for chemotherapy-induced nausea and vomiting.

“There’s a reasonable amount of evidence showing that some of these are better than placebo for relief of these symptoms,” Dr. Grossman said. “That said, the jury’s out as to whether they are any better than our other antiemetic agents. And there are no studies comparing them to neurokinin-1 inhibitors, which are the newest class of drug often used by oncologists for this indication. There is also no good evidence about inhaled plant cannabis.”

Studies of oral cannabinoids for multiple-sclerosis–related spasticity have demonstrated a small improvement on patient-reported spasticity (less than 1 point on a 10-point scale), but there was no improvement in clinician-reported outcomes. At the same time, their use for weight loss/anorexia in HIV “is very limited, and there are no studies of plant-derived cannabis,” Dr. Grossman said.

According to the National Academy of Sciences report, some evidence supports the use of oral cannabinoids for short-term sleep outcomes in patients with chronic diseases such as fibromyalgia and MS. One small study of oral cannabinoid for anxiety found that it improved social anxiety symptoms on the public speaking test, but there have been no studies using inhaled cannabinoids/marijuana.

The health risks of medical marijuana are largely unknown, Dr. Grossman said, noting that most evidence on longer‐term health risks comes from epidemiologic studies of recreational cannabis users.

“Medical marijuana users tend to be older and tend to be sicker,” she said. “We don’t know anything about the long-term effects in that sicker population.”

Among healthier people, Dr. Grossman continued, cannabis use is associated with increased risk of cough, wheeze, and sputum/phlegm. “There’s also an increased risk of motor vehicle accidents,” she said. “That is certainly a concern in places where they’re legalizing marijuana.”

Cannabis use is associated with lower neonatal birth weight, case reports/series of unintentional pediatric ingestions, and a possible increase in suicidal ideation, suicide attempts, and completed suicides.

“The evidence is very limited regarding associations with myocardial infarction, stroke, COPD, and mortality,” she added. “We don’t really know.”

Dr. Grossman reported having no financial disclosures.

dbrunk@frontlinemedcom.com

Evidence for medical marijuana largely up in smoke