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10 Articles in this Series
An AAPM 2019 Preview
APRNs/PAs in Pain Medicine SIG Gets Underway
Cannabis Has Entered Pain Management and Is Here to Stay: What Clinicians Need to Consider
Managing Pain in Marginalized Populations, including Ethnic Minorities, LGBTQ, and the Obese
Neuromodulation: A Roundtable on Current Best Practice & Key Questions
Pro/Con: CGRP Antibodies and Treatment Choice for Chronic Migraine
Pro/Con: Conservative Care is the Best Route for Chronic Pelvic Pain
Pro/Con: CRPS - Use Everything but Stimulation
Pro/Con: Ketamine for Complex Regional Pain Syndrome, Neuropathic Pain, and More
Pro/Con: Radiofrequency Denervation is Effective (The MINT Studies)

Cannabis Has Entered Pain Management and Is Here to Stay: What Clinicians Need to Consider

with Mark A. Ware, MBBS, MRCP (UK) and David J. Casarett, MD

The American Academy of Pain Medicine kicked off its 35th annual meeting, held in Denver, by focusing one of the first keynote sessions on cannabis for pain. Despite the budding scientific evidence for its therapeutic benefits, more and more patients are seeking out the substance as states legalize its use. As a result, clinicians are being pushed to better understand its medicinal effects—and risks.

Leading the fireside-style chat was AAPM Program Co-Chair Patrick Tighe, MD, an associate professor of anesthesiology at the University of Florida. On the panel: David J Casarett, MD, professor of medicine at Duke University, chief of palliative care at Duke Health, and author of the book Stoned: A Doctor’s Case for Medical Marijuana; and Mark A. Ware, MBBS, MRCP (UK), who until recently served as an associate professor of family medicine and anesthesia at McGill University and now serves as the CMO of Canopy Growth Corporation in Canada. Dr. Ware also led a nonprofit on cannabinoids and has advised the Canadian government on cannabis policies. Below are a few highlights* of the conversation, with topics posed by Dr. Tighe. (See also, PPM's April/May 2019 special reports on the endocannabinoid system, talking to a dispensary, and talking to patients about medical marijuana.)


Understanding the Evidence for Cannabis in Pain Management

Dr. Ware: The current challenge we have is in interpreting the limited evidence that is available. At least a dozen systematic reviews have come out in the past two years alone, with some showing that cannabis can benefit neuropathic pain and some showing that cannabis is not helpful for neuropathic pain and may, in fact, be harmful. So, we are stuck in a place where the evidence is not providing any clear base or direction. Thus, we need to get more evidence quickly.

Dr. Casarett: I am fairly optimistic that there are benefits to using cannabis to treat pain, particularly neuropathic pain. The one review that made me a bit less enthusiastic was the 2018 Cochrane review which included unpublished studies but excluded short-term trials. That said, looking through the literature on this topic is like a contact sport—you need to dive into it. You cannot simply read an abstract and change your practice, you need to look at the methods and balance the conflicting conclusions.

Dr. Ware: I agree, and it is also important to review these studies in context—much of the safety data applies primarily to recreational use of marijuana (eg, psychosis, substance abuse, driving) and, yet, these harms get chunked in as potential risks on the medicinal side when they may or may not be relevant…. The point is, that as much as we talk about opioids as a class, I think cannabinoids should also be talked about as an emerging drug class. There is a huge family of these compounds, and as regulations relax, we are just beginning to understand how to use this family as a toolbox. We cannot talk about cannabis as one thing—it’s THC, it’s CBD, it’s combinations thereof—and clinicians need to learn this vocabulary.


Cannabis and Mental Health Risks

Dr. Ware: I recently published a review with Dr. Gabriella Gobbi at McGill University in JAMA looking at cannabis use in adolescence and its potential impact later in life regarding depression and suicide ideation ) and there were correlations. Whether cannabis was the implicating factor or there were other factors that led these individuals to using cannabis at age 12 was unclear. Certainly cannabis use at a young age, before 15, affects the developing brain and this is a public health concern that warrants more research and more attention. But beyond adolescence, the risks of cannabinoids on mental health drop off.

Dr. Casarett: One Australian study found an increased risk of cannabis use among adolescents with schizophrenia, leading to questions around genetic risk, self-medication, etc, that make the associations between mental health and cannabinoids even more difficult to understand. Overall, I think we need to be alert to these risks but not paranoid about them.

Dr. Ware: Some of our work (at Canopy Growth) involves surveying individuals who use medicinal marijuana about why they use it. Pain is most common, insomnia is second, and mood is third (eg, anxiety and stress). THC appears to have the potential to precipitate anxiety. CBD at high doses has been shown in fairly good clinical trials to have anti-anxiety effects. By combining and balancing them…it may be possible to mitigate some mental health risks. This area of research is being explored, but unfortunately, when it comes to risk of psychosis and cannabis use, there is no quick genetic test to say to a patient, “Yes, you’re safe.” Until biomarkers are known, family history can be a powerful screening tool. In Canada, an individual with a first-degree relative diagnosed with psychosis would not be a candidate for cannabinoid therapy.

Dr. Casarett: There are opportunities here to investigate and to consider mental health in cannabis research and use, especially as many chronic pain patients present with complex issues and comorbidities. There are no easy fixes and cannabinoid medicine must be approached in the same way one would think about nonpharmacological therapy.

Dr. Ware: We have learned how pain and addition medicine need to work together, and regarding cannabis we have to work more closely with psychiatry to inform risk and benefit discussion. However, the most common patients in pain management are adults who are beyond an initial risk of psychosis. Many have perhaps already tried cannabis their lives and I don’t think we need to throw psychosis as a top new concern regarding cannabis use. In Canada, we have not witnessed a surge in psychotic episodes since the country allowed for medical cannabis. If anything I would worry more about cannabis addiction than psychosis. And in this regard, it is important to keep reporting what we see with cannabis use in our patients and to monitor them closely.

Patients should start with cannabidiol (CBD) which does not contain the psychoactive THC, but there is no evidence for specific starting doses or strains.

Opioids, Cannabis, and Addiction Comparisons

Dr. Casarett: It is possible to have a fatal overdose of opioids, whether illicit or not, but it is not possible to have a fatal overdose of cannabis. Certainly, there are poor behaviors associated with cannabis use and cannabis addiction is possible, as Dr. Ware just noted, but most of the negative data around cannabis comes from recreational settings.

Dr. Ware: Screening for cannabis use disorder according to the DSM-V should be used, especially in those patients that come in saying they have been using it a lot, that it is the only thing that works for them, and asking exclusively for medical authorization for it. If a patient meets the criteria, then we need to refer them for help. On the other hand, public health data has shown reductions in opioid mortality where cannabis is available—this is an interesting signal but what is missing is the clinical trial data demonstrating cannabis as an opioid- sparing therapy. If there’s even a slim chance that cannabinoids may mitigate some of the impact of the opioid crisis, then I believe we have a moral obligation to pursue it.

Dr. Casarett: To add to this point, some studies have shown that patients with opioid use disorder (OUD) have switched to cannabis and were able to get off opioids. Other studies have found that many patients are motivated to use cannabis in order to reduce their opioid consumption.  There’s also emerging evidence from Vancouver that patients on medication-assisted treatment (MAT) for addiction may be more likely to stay in the program if they use cannabis. Those data are preliminary, and we do not have randomized trial evidence, yet. Nevertheless, there is clearly a complex relationship here that we need to continue to examine. In fact, the community needs to consider removing the restriction on cannabis use from opioid patient agreements. Often, patients testing positive for cannabis as part of their opioid agreement get dismissed from the clinic—this may not be the best course of action.

[See PPM's new literature review on addiction medicine and relapse prevention]

Talking to and Advising Patients about Cannabis

Dr. Ware: When patients ask about cannabinoid use, they are often asking for the right reasons—they want to try it. Ask them why they find it interesting and what they hope it may help. In some cases, the patient may have already tried it, researched it, and know more about it than we do. Be open and get more informed so that we, as clinicians, can have these conversations meaningfully. It is also important to express to the patient what we do not know clinically and to make clear that there is a lack of evidence. Advise them to start slow and at low doses. Typically, patients start with cannabidiol products (no THC) but there is no specific evidence for starting doses or strains for pain management. We have to rely on clinical experience and patient response.

Dr. Casarett: The fact is, cannabis is getting more attention so we are bound to hear about more risks, more associations, and to get more questions about its use. It will take time for data to catch up to some of the smaller studies and anecdotal reports. This will be the world of cannabis work for at least the next five years.

*Note: All quotes/statements here have been paraphrased for style and clarity.

Next summary: Managing Pain in Marginalized Populations, including Ethnic Minorities, LGBTQ, and the Obese
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