In July, Health Canada announced it was modifying its rules for medical marijuana and would allow producers to sell oils and fresh leaves, as well as the dried plant that is currently available. The rule change, mandated by a Supreme Court decision in June, will allow patients prescribed marijuana to consume it orally rather than smoke it. Even as Health Canada loosens restrictions, it maintains that marijuana is not an approved medicine, nor does it endorse its use for any specific disease. Of course, that hasn’t done anything to slow down its increasing popularity.

Claims have been made in recent years that marijuana can be used for a wide range of conditions, including cancer, glaucoma, chronic pain, multiple sclerosis, HIV, Alzheimer’s disease and post-traumatic stress disorder, among others. Support has come from high-profile personalities such as Dr. Sanjay Gupta, who became an advocate for medical marijuana with his 2013 documentary, Weed. For their part, many patients and their physicians claim to have seen dramatic improvements with cannabis. Michael Dworkind, medical director of Santé Cannabis in Montreal, Quebec’s first medical marijuana clinic, has treated many patients with chronic pain or palliative cancer and has seen dramatic results. “As a physician, I see the vast majority of my patients benefiting, and it’s very heartening.”

But some doctors and researchers are raising concerns about how little we know about marijuana’s efficacy, how few reliable studies there are, and how expectations might not match the evidence. Skepticism about the health benefits of marijuana have been bolstered by a recent meta-analysis in the Journal of the American Medical Association commissioned by the Swiss Federal Office of Public Health. After reviewing 79 randomized trials, with 6,462 patients, researchers found evidence of moderate quality to suggest marijuana helps for chronic nerve pain, nausea due to chemotherapy, and spasticity due to MS—but that was it.

For many other diseases, including glaucoma, insomnia and anxiety, researchers found no evidence, or low-quality evidence, to support its use. Robert Wolff, the study’s co-author, points out that if marijuana were a new medication, the lack of evidence means it would not be approved by the FDA or Health Canada. “I think the same principle should be applied as for normal drugs,” says Wolff. “It should be treated as a [prospective] medication, with all the pros and cons.”

But the absence of evidence is not the evidence of absence, according to Mark Ware, associate professor in family medicine at McGill University. “I hope we don’t interpret the lack of evidence as evidence that it doesn’t work. The lack of evidence means we don’t have the studies of whether or not it does work,” he says. Ware heads up the Quebec Cannabis Registry, which tracks patients using medical marijuana. He hopes the data he collects will help narrow what he calls a severe knowledge gap associated with medical cannabis. But other researchers aren’t so optimistic.

“I think the evidence is rather flimsy,” says Dr. Ley Sander, professor of neurology at University College London’s Institute of Neurology in Britain. Sander’s focus is on seizure disorders, and he’s a principal investigator of a trial looking at cannabis as a treatment for epilepsy. He cautions that expectations may be outpacing reality. “I think a lot of people will be disappointed when things come out, because I don’t think we’ll find anything dramatic for epilepsy.” He explains that many people with seizures may not require long-term medication, and many others do well with the medications they already have. Twenty to 30 per cent of patients have symptoms that are not well controlled and, for some of them, cannabis may prove helpful, particularly if their seizures are caused by a genetic condition. “But I don’t think it’s going to be a magic bullet,” he adds.

As it stands, many significant questions remain. Most of the research done to date has used oral cannabinoids, prescription pills that contain extracts from marijuana plants. In Wolff’s study, only two of the 79 clinical trials used smoked marijuana, with the rest using these oral cannabinoids. “I don’t think it’s right to extrapolate [these findings] to medical marijuana,” says Deepak D’Souza, professor of psychiatry at Yale University. He says we can’t take studies done with prescription medications and use them to justify smoked marijuana. “You have to test exactly the same product you want to sell.” He explains that while oral prescription cannabinoids contain fixed doses of specific molecules, the marijuana plant contains more than 400 molecules of uncertain and variable dosages.

Another major issue is safety. Wolff’s review found medical cannabis was associated with an increased risk of many side effects. While most were minor, such as dry mouth and dizziness, there was also a risk of major adverse psychiatric events, including hallucinations and confusion. In the 1980s, Pfizer developed an oral cannabinoid called levonantradol, which was very effective at reducing pain and nausea. But it had disturbing side effects and caused psychosis and paranoia in some patients, so the drug was never brought to market.

A number of studies have also linked heavy marijuana use in early adolescence to schizophrenia later in life. But Ware cautions we can’t use studies of recreational marijuana use and apply them to the medical setting. “They’re using the drug differently. They may be using smaller amounts [or] they may be using it less frequently,” he explains. He recently published an observational study in the Journal of Pain where patients prescribed medical cannabis for chronic pain had no major side effects. They did experience minor side effects like nausea and drowsiness. They also had small decreases in lung function.

Uncertainty still remains about both the benefits and risks of medical marijuana, with the medical issue often clouded by the legal debate. According to D’Souza, more research is needed before governments approve its use. But he also says governments should support that research. “We need more evidence, because we really jumped the gun and put the cart before the horse.”