What is the evidence for medical use of cannabis?

“Results reflect the … relative dearth of high-quality evidence related to cannabis for therapeutic purposes”

“The level of evidence for the use of medical marijuana among people with disabilities varies greatly and has a clear lack of methodologically sound studies”

“Evidence is gathering … but further research is required to declare cannabinoids a medicine”

“These studies suffered from multiple limitations, including selection bias, lack of standardized dose and route of administration, absence of blinding, recall bias and lack of a control population”

“The long-term safety profile of chronic cannabis use has not been well defined, mainly due to the heterogeneity of preparations, varying routes of administration, and the lack of controlled studies addressing safety”

“Evaluation of these low-quality trials … was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size”

These are some of the things the experts are saying about the research into medical uses of cannabis to date. To prepare this article, I read 11 “review” articles — articles that pull together all of the research out there and reach conclusions.

The authors are unanimous in saying there is little research, and many of the studies that have been done are really small — less than two dozen patients. Some lack another treatment for comparison — either a placebo or another drug. Other studies can’t be blinded, because patients can tell whether they are getting cannabis, either because they are smoking it or they feel stoned. Others are “observational” studies (some patients are given cannabis and the researchers see what happens), considered the poorest type of evidence.

But there is some good research, and it shows that cannabis might be useful in a few health conditions:

  • Pain
  • Epilepsy
  • Inflammatory bowel disease (Crohn’s disease and ulcerative colitis)

These medical uses of cannabis are not just based on folklore (or, in this case, folk-singer lore). Science has shown that some of the chemicals in cannabis (cannabinoids) mimic natural chemicals in the human body that are important in the nervous system and the immune system. This is why its use is being taken seriously as a potential addition to the drugs we already have.

Pain

The toughest pain to control is cancer pain. A review of five randomized controlled trials looked at cannabis to treat this type of pain. Although one of the studies didn’t find any difference between cannabis preparations containing both THC and CBD (nabiximols) and placebo, there was definite effect in two larger studies with more than 150 patients each. Two earlier studies that had looked at short-term effects in small numbers of patients also found an effect. This review was funded by a Canadian medical cannabis company but was conducted with Sunnybrook Health Sciences Centre and the University of Toronto, so the oversight, ethics and evidence should be solid.

Epilepsy

I have known someone with very serious epilepsy who must cope with several seizures each day. This type of disability limits a person’s life and can even pose a danger. In some cases, the well-established drugs that control epilepsy in most people don’t work or cause serious side effects.

Four reviews of the research found evidence that cannabis preparations can reduce or even stop seizures in people with severe seizure disorders. But the effectiveness seems to vary from patient to patient.

A review that looked at cannabis research for many different disabilities found robust evidence only for epilepsy and pain. Another review that looked specifically at the non-intoxicating cannabinoid CBD for epilepsy showed that it was effective but also showed high rates of side effects, including sleepiness, loss of appetite and diarrhea. A third review found positive effects of CBD in the worst types of epilepsy: Dravet syndrome and Lennox-Gastaut syndrome.

Inflammatory bowel disease

There was a lot of hope that cannabis could help with IBD through its effects on the immune and gastrointestinal systems, but findings are mixed.

A review of five studies (only two of which were high-quality and all of which were small) found positive and remarkable effects on symptoms of IBD. However, two systematic reviews (one for Crohn’s disease and one for ulcerative colitis) by the Cochrane Collaboration — well known for its high-standard reviews — found that the effects were uncertain, the studies small, and conclusions unreachable. However, because of the positive findings of some studies, treatment of IBD needs to be tested in larger groups.

Why not more, better, larger studies?

That’s the question. When I attended a panel on medical cannabis earlier this year (2018), one of the panellists representing a cannabis company buttonholed me afterward about the difficulty in conducting studies. He pointed out that the best level of evidence is provided by randomized controlled trials involving hundreds or thousands of patients. But running those trials is incredibly expensive. He also argued that it is difficult to use placebos when testing cannabis, since those taking cannabis may be smoking it and it may be unethical to let patients go without some kind of treatment. This also means it might be impossible for the trials to be double-blinded — when neither patients nor researchers know who is getting the drug and who the placebo or comparison drug.

These are good points, but they sound like companies are throwing up barriers to running studies.

First, many randomized controlled trials compare the test drug with the standard treatment or best treatment (“gold standard”) rather than with a placebo. This is certainly the case for drugs for mental health problems, as it would be unethical to let a serious mental health problem go untreated. So, trials do not need to use a placebo.

Also, many trials are single-blinded rather than double-blinded. That is, the patients can figure out what they are getting, but the researchers don’t know who is getting what and aren’t influenced by that knowledge. In many trials, this is necessary, if not optimal.

The real issue is money. Running the kind of studies that you need to submit to Health Canada to have your drug recognized as a safe and effective treatment for a particular condition takes years and millions of dollars. Right now, cannabis companies are not that rich.

But in Canada the cannabis companies have formed a consortium that could fund trials. As well, disease foundations in Canada and other countries (like, the one to the south) are interested in the promise of cannabis, and they put money into research. With its open regime, Canada is a good place to carry out international studies of medical cannabis, which would not face the legal hurdles that exist in many other countries.

There are many conditions for which safe and effective drugs are needed. If cannabis can help, it should be prescribed and monitored by doctors to ensure it works for patients, and it should be covered by drug plans. It should not be bought at a dispensary for self-treatment, often by patients who can’t afford it.

As I mentioned to the cannabis company representative, doctors were burned on opioids. The manufacturers claimed opioids weren’t addictive, which wasn’t true. Studies would give doctors full information on cannabis’ effects and risks, so they could inform their patients. Doctors and patients deserve no less.

 

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