There is “insufficient” evidence supporting the use of cannabis or cannabinoids for most medical purposes, a new review has concluded.

“We reviewed the totality of the evidence—over a thousand studies with emphasis on randomized trials, meta-analyses, and systematic reviews,” Dr Kevin Hill, one of the review authors, and director of addiction psychiatry at Beth Israel Deaconess Medical Center, and a professor of psychiatry at Harvard University, told Newsweek.

He said that “beyond the FDA-approved indications, the evidence for cannabis and cannabinoids as a medical treatment is limited.”

The review was published online in the peer-reviewed medical journal JAMA Network on November 26.

There has been increasing use of cannabis and cannabinoids for medical treatment in recent years. It has gained popularity among cancer patients, for managing nausea, pain and reduced appetite, and it is favored among patients with chronic pain for its analgesic properties.

However, its use medically has gathered some concern, as while certain patients may experience benefits, some medical professionals have said that there is not enough research to determine if the positives outweigh any future negatives.

More recently research has also highlighted how cannabis use among cancer patients may reduce the effectiveness of immunotherapy treatments, and that its use can impact female egg quality and embryo development.

After the Senate passed its funding package to end the U.S. government shutdown, which included a measure that will lead to the banning of many THC products, the issue of cannabis use has been in the spotlight.

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The review found that 27 percent of adults from the U.S. and Canada have used cannabis for medical purposes, while 10.5 percent of Americans report using cannabidiol (CBD) for therapeutic purposes.

“Cannabis and cannabinoids like CBD have a broad range of effects, so, with so many people suffering from medical problems, it is not hard to see why they might consider cannabis and cannabinoids as treatments,” Hill said.

However, he said that “the evidence is not strong” for their use medically.

While doctors may “consider cannabis and cannabinoids as third-line treatments in various clinical scenarios,” Hill said, “the lack of evidence coupled with significant risks means that, most often, the risks outweigh the benefits.”

The review found that almost a third of adult users of medical cannabis go on to develop a cannabis use disorder—a complex condition that is a type of substance use disorder, where a patient can experience a problematic pattern of cannabis use that causes them distress or impairs their life.

It also found that daily inhaled cannabis use compared to nondaily use was associated with higher risks of coronary heart disease, heart attack, and stroke,

“The adverse effects of cannabis upon one’s physical health are becoming more well-defined,” Hill said.

He said that the purpose of this review was to provide clinicians and patients with “better information with which to have sensible, evidence-based conversations,” conversations about medical treatment which he said should take place between doctors and patients, and “not between budtenders and customers in dispensaries.”

Jonathan Caulkins, a professor of operations research and public policy at Carnegie Mellon University, who was not involved in the review, told Newsweek that while there is “high-quality evidence supporting certain very specific medical uses,” most medical use is “predicated on much less evidentiary basis, and below what is expected for FDA approval.”

He said that what is “important” about this review is that it helps “counter the messaging from cannabis treatment advocates, who promote the good news, and the hopes, without balance or caution.”

“The actual situation is nuanced, and more gets written that pushes for an overly optimistic view of cannabis’ medical value,” he said.

Yasmin Hurd, chair of translational neuroscience and the director of the Addiction Institute at Mount Sinai, also told Newsweek that the findings are “notable” because it “confirms what has been previously published from other reviews and consensus reports like those from the National Academies, noting that there is insufficient evidence for the use of cannabis to treat most medical conditions.”

While the authors have “done a very comprehensive and in my view very useful review of this topic,” Dr Igor Grant, a professor of psychiatry and director of the HIV Neurobehavioral Research Program and Center for Medicinal Cannabis Research, at the University of California, San Diego, told Newsweek, “it is clear from the way the article is written that the authors have significant concerns about the use of medicinal cannabis, and as such have tended to emphasize many of the negatives, including potential side effects.”

He said that this “does not mean that the side effects are not there, nor does it negate the fact that evidence for efficacy of medicinal cannabis is weak in many areas. But there does seem to be a definite slant.”

He also said that while this review highlights cardiovascular risks, other research has also shown there is “actually no statistically reliable evidence to suggest that cannabis users suffer more cardiovascular risk, including no effect on hypertension, myocardial infarction, and presence of coronary atherosclerosis.”

Caulkins told Newsweek: “We customarily expect medicinal drugs to be produced in a way that guarantees consistency from dose to dose. Every pill in a bottle of pills that is prescribed by a physician, manufactured by a pharmaceutical company and distributed by a licensed pharmacy should have essentially the exact same dose. With the exception of the FDA-approved and regulated cannabinoids (which account for a tiny share of all consumption that is described or understood to be “medical cannabis”), there is not that same quality control for medical cannabis.”

He added: “Cannabis smoke contains known carcinogens. Sometimes good medical practice exposes patients to carcinogenic risk, notably radiation treatment does. But we do that carefully and knowingly, because the risk of untreated cancer is greater than the risk that radiation therapy will create new cancer. But given that in many cases the upside benefit of medical cannabis is not well established, it is striking how cavalier the system is with respect to known carcinogens present in cannabis smoke. For most categories of consumer products, the presence of known carcinogens is sufficient to have that product taken off the shelves, even if there are not epidemiological studies documenting effects on cancer rates at the population level. For whatever reason or reasons, we collectively seem surprisingly unconcerned about that risk regarding smoked cannabis, medical or non-medical.”

Hurd told Newsweek: “There remain numerous concerns about cannabis for medical use since there is so little known about whether it works, what particular conditions it might be helpful to treat and what dose and dosing regime for clinicians to recommend. In addition, there are also concerns that individuals will use ‘medicinal cannabis’ obtained from sources where the contents are not verified and cannabis with high THC concentration has well known significant side effects. Cannabis should be used with caution in medical settings. As such, like many medicines, especially where there is very limited information available, it is best to start low dose and go slow. Also, cannabis should not be the first line therapy and instead used only for conditions where conventional therapies have failed.”

She added: “It is important that the public also begins to better understand that cannabis is a very complex plant with hundreds of chemicals whereas ‘medicine’ is normally a product that has specific, well studied components. Also, cannabis is different from specific cannabinoids, like cannabidiol (CBD), which has FDA approval for the treatment of certain epilepsy conditions.”

Grant told Newsweek: “While I agree that physicians who are counseling patients about potential use of cannabis for various indications need to both warn patients about lack of evidence in many cases, the possibility of side effects, and certainly evaluate a patient in the event they have major psychiatric or substance use disorder, there are, as they note protocols for doing this, and in some ways, assuring safety. I believe also that the risk of people who use medicinal cannabis, who are often people who are older with various kinds of chronic conditions, is rather low that they will systematically increase their use to the point of developing a cannabis use disorder. Cannabis use disorder is real, and a concern, but very unlikely to be a problem in the clinical setting. The article tends at times to conflate recreational and medicinal use: that’s a bit like using data from opioid addiction to comment on appropriate use of opioids in a clinical setting.”