June 17, 2019
3 min read

Marijuana, Rheumatology and Clinical Equipoise

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We are extraordinarily fortunate this month to have an esteemed group of clinical scientists participate in our roundtable discussion, “The Cannabis Frontier: As medical cannabis moves mainstream, are rheumatologists prepared?” This is an ever so timely topic as evidenced by the daily encounters I am now having with patients, with an array of problems, who want to discuss the potential use of “medical marijuana” for their condition.

A year ago, I was not very well informed on the clinical science of medical marijuana and most of what I knew came from the wave of anecdotes, which has recently been dubbed the “vernacular” cannabis movement. These anecdotes are teeming with many natural signs of danger, such as reporting efficacy in virtually all diseases which heretofore have seemed untreatable. It is in this light that I am still searching for a reasonable way forward in my discussions with patients who are seeking counsel regarding unmet health care needs.

Leonard H. Calabrese
Leonard H.

The science of cannabis is extraordinarily complex; “Cannabis” itself is a generic term encompassing marijuana, tetrahydrocannabinol (THC) and cannabidiol (CBD). However, this complexity is generally lost on patients with unfulfilled health care needs ranging from pain to anxiety, depression, addiction and beyond. I have also tried to wrap my head around the basic immunology of cannabinoids and it is incredibly complex, with far-reaching effects on both innate and adaptive immune responses that are contextual, thus making simple conclusions problematic.

Add to this the legacy of antediluvian U.S. government drug policy which has thrown up just about every road block possible to performing creditable research in this area and here we are. We have no clear evidence of the efficacy of these compounds in most diseases, save a few. We also have very little evidence of harm — especially for CBD — but we do have concerns for cognitive and motivational concerns with marijuana and a youth population at risk for serious psychiatric disorders as well.

Given these conflicting forces, what are we to do? In modeling of shared and informed decision-making there are two polar opposites: On the one hand, the provider can be dogmatic and tell the patient to “do what I say because I say it.” On the other hand, the provider may throw up their hands, say “it’s your choice,” and default on providing guidance. We all recognize that neither model is what patients need or want and thus the middle path (as always) is most desirable.


In 1987, the term “clinical equipoise” was introduced by Benjamin Freedman, implying a genuine uncertainty within the medical community about a given treatment. “Clinical equipoise” has been used as the ethical justification for conducting clinical trials — if we knew for sure a treatment was good or bad, we would not be justified in supporting human experimentation.

I clearly have clinical equipoise when it comes to cannabinoid use in clinical medicine for many conditions I see — especially chronic pain. Do I recommend it? Not really, but when asked, I explain my position of clinical equipoise and go over the potential for harm. I must say that I find little evidence of potential harm for CBD (as long as it’s a quality product, but that is another concern) which is the therapy that seems to be of the greatest interest to most patients, as opposed to marijuana which, with its more prominent psychoactive effects, is instead preferred for recreational use.

Finally, the patina of medical marijuana is crumbling by the hour in states that have legalized both medical and recreational use. Why would anyone in their right mind go through the dance that is being orchestrated for medical use when there are stores on every corner, selling the entire spectrum of compounds, for recreation? I believe the end is near for most of the demand on the medical side.

I close by saying that, for now, I will hold the middle ground. I will maximize my efforts to avoid condoning patients harming themselves and I will continue to ask for careful follow-up, so I can add my own observations to the evolving field. I will also continue to strongly advocate for what is really needed: Quality research. We should be embarrassed as a nation for how our politicians and regulatory agencies have handled this field so far. The people are speaking with their feet so get on board.

Let me know your thoughts on this contentious topic via email at calabrl@ccf.org or on Twitter @LCalabreseDO.

Disclosure: Calabrese reports serving as an investigator and a consultant to Horizon Pharmaceuticals.

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