The Pain Dilemma: Cannabis Versus Medicine?

As thousands of patients across the country try to manage their chronic pain with myriad medications, they are also juggling side effects, possible toxicity and sometimes even overdose, opioid addiction, and an overall quality of life issue.

According to the Centers for Disease Control (CDC), from 1999–2019, nearly 450,000 people died from overdoses involving opioids, including prescription and illicit opioids. Perhaps even more alarming is that opioids were involved in nearly 47,000 deaths in 2018, almost six times the number of opioid-involved overdose deaths in 1999. And the rate of addiction and overdoses due to opioids continues to rise and devastate families, communities, and patients with chronic conditions (1). As researchers from Oregon Health & Science University, Portland, said, “Unless the nation develops an increased tolerance to chronic pain, reduction in opioid prescribing leaves a vacuum that will be filled with
other therapies” (2).

As such, researchers, scientists, and other interested parties have been investigating cannabis’ role in chronic pain. Kevin Boehnke, PhD, a research investigator at the Chronic Pain Institute Research Center in the anesthesiology department at the University of Michigan took an interest in cannabis research as a side project during his PhD, and then switched his energy to cannabis full time in 2017 when he began a research fellowship at the Chronic Pain and Fatigue Research Center. Boehnke has been tackling questions such as what health conditions are patients using cannabis for, which dosage formats are they using, are patients reducing their use of opioids, and does it help chronic pain. We recently discussed some of the research surrounding those questions with Boehnke and the impact his research might have on the broader medical cannabis community.

Chronic Pain, Opioid Reduction, and Cannabis

Boehnke started his PhD career in public health studying water quality and the transmission of bacteria in water. Although this sounds like a far stretch from his future work with cannabis, he said it got him thinking at the population level and about harm reduction. And after hearing a talk about cannabis, he was curious why the talk only focused on the negative and not on the therapeutic effects of cannabis.

In 2013, Boehnke and Dan Clauw, MD, director of the Chronic Pain and Fatigue Research Center at the University of Michigan—along with the help of a local dispensary—administered a survey. The survey revealed that many medicinal cannabis patients were reducing their opioid use after they started using cannabis. Not only did these findings start Boehnke’s quest to find out more about people using medical cannabis and chronic pain, it also changed his perception of medical cannabis. “Cannabis is a very versatile medicine,” he said. “People use it for sleep, they use it for pain, and they use it for managing mood, all of which interface with chronic pain.”

In 2013, Boehnke and two other investigative researchers from the University of Michigan, Ann Arbor, conducted a retrospective cross-sectional survey that evaluated the use of medical cannabis and decreased opiate medication in 185 patients with chronic pain. The data collection went from 2013–2015, and results were published in 2016 (3). Among the study participants who utilized a medical cannabis dispensary in Michigan from November 2013 to February 2015, medical cannabis use was associated with a 64% decrease in opioid use (n=118), a decreased number and side effects of medications, and an improved quality of life (45%).

Although the study design is limited due to its cross-sectional setup, Boehnke explained that for patients to say that, on average, they had a 64% reduction in opioid use is pretty large. “When we think about how many lives are impacted by the opioid crisis, one way to target that and reduce people’s use of opioids is to either not prescribe them in the first place or offer a safer alternative—something that allows them to effectively lower their dose, so they can lower their risk of overdose or toxicity," Boehnke said.

Boehnke conducted a second, larger survey in 2019 (N = 1321) (4). This study revealed patients’ reasoning for substituting with cannabis. Approximately 80% reported substituting cannabis for traditional pain medications (53% for opioids, 22% for benzodiazepines), citing fewer side effects and better symptom management as their rationale for doing so. The study also found that medical-only users were older, less likely to drink alcohol, and more likely to be currently taking opioids than users with a combined recreational and medical history.

“If patients report that cannabis is more effective, they tolerate it better, and it has a favorable safety profile compared to their other medications, then that's a win from a treatment standpoint,” said Boehnke. “These results, combined with many other studies showing the same, validated that this is a place we should be focusing our energies. The question becomes: How do we do this more effectively and help physicians, patients, and ideally scientists continue to engage with the space?”

Cannabis Use-Frequency and Clinical Outcomes

When you talk about cannabis as a therapeutic remedy, it’s difficult not to mention dosing (how much is too much?), dosing formats (edibles versus smoking), the side effects of “getting high,” the safety of smoking and vaping, and, of course, its efficacy in abating pain and other symptoms.

In a recent paper published in the Journal of Pain, Boehnke and five other researchers conducted a cross-sectional study that observed whether daily cannabis-use frequency was associated with pain severity and interference, quality of life measures relevant to pain, for example, anxiety and depressive symptoms, and cannabis-use preferences (5). According to the paper, “Heavy medical-only use participant consumption patterns showed greater preference for smoking, vaporizing, and high tetrahydrocannabinol (THC) products. In contrast, light medical-only use participants had greater preference for tinctures and high cannabidiol (CBD) products.”

Their findings suggest “that lower daily cannabis-use frequency is associated with a better clinical profile as well as safer use behaviors, e.g., preference for CBD and non-inhalation administration routes. These trends highlight the need for developing cannabis-use guidelines for clinicians to better protect patients using cannabis.”

But Boehnke warns that due to the study design, selection bias, and focus on chronic pain, these findings have limitations. “This was not a longitudinal study; it was a single snapshot in time, a cross-sectional study,” Boehnke stressed. “We don’t know if those use behaviors led to worse clinical outcomes, but what we can say is the people who were using cannabis more frequently seemed to have a more impacted clinical profile at the time the study was conducted. It’s possible they were overusing cannabis and that overuse—especially because they were more likely to smoke or vape than use tinctures or topicals—negatively impacted them. It’s [also] possible they were not having as effective pain management or perhaps worsening their symptoms.”

He also said it’s possible these folks were the ones with worse clinical symptoms initially, and as a result, they had a more impacted profile even after using cannabis. “It’s one of those studies that has interesting findings, but contextualizing it is really important,” he said. “From a harm-reduction perspective, there’s a lot of concern about smoking as a primary way of ingesting cannabis. So, if you can use these non-inhalation routes and obtain a similar effect, that's a useful strategy for reducing harm.”

Another concern is using high amounts of cannabis daily via smoking or vaping—the issue is that the effects don’t last long, so patients are often smoking multiple times a day, resulting in "quick spikes and tapers of the THC high. With frequent use, this may contribute to dependence or abuse-like behaviors," Boehnke said. In contrast, “folks in the less frequent-use category were more likely to use CBD-dominant products, which, from a harm-reduction perspective, is also quite interesting and important, because CBD doesn’t have the kind of addiction and abuse potential as THC,” he explained.

His hope is that this study can help stimulate conversations with their patients and be able to offer tips and advice on safer practices. Something like, “Let’s come up with a treatment plan, and in X number of weeks, I’ll follow up to see how it’s going”—as they would with any medication. Boehnke said he feels “all too often what happens is physicians don’t want to talk about it. They refer their patients to addiction services, and sometimes they won’t keep seeing them as long as they’re using cannabis. Some institutions have so-called no-pee, no-pill policies—if a patient tests positive on a drug test, then they can’t get some of their medication.”

Qualifying Conditions of Medical Cannabis Patients

So, what medical conditions are patients using cannabis for? In an effort to answer this question, Boehnke and a team of three analyzed state registry data to provide nationwide estimates characterizing the qualifying conditions for which patients are licensed to use cannabis medically. (6)

“We wanted to get a big-picture understanding of what people were using cannabis for nationwide,” Boehnke said. “We went to all the states’ website that had legal medical cannabis and collected their publicly available reports. If they weren’t available, we emailed the offices to collect any kind of data they had, and we put it all together and plotted the data over time and looked at trends in those data.”

Their findings revealed that chronic pain was the most common qualifying condition reported by medical cannabis patients (64.5% in 2016). And of all patient-reported qualifying conditions in 2016, 84.6% had either substantial or conclusive evidence of therapeutic efficacy.

“Lots of people use cannabis for chronic pain, muscle spasms or spasticity, multiple sclerosis, and chemotherapy-associated nausea and vomiting,” Boehnke said. “The big takeaway is a growing number of people are using cannabis, and the reasons they’re using it actually align with what we know from the evidence.”

But, what Boehnke pointed out is there are many other conditions available under state law with little or no evidence that cannabis is actually helpful for treating. “It’s really important to be judicious and thoughtful about how we’re considering cannabis to medicine,” he warned. “So, it can be used appropriately instead of being thrown against every symptom that somebody has, even if it might not be helpful and in fact, might be keeping them away from a treatment that is helpful.”

Cannabis as Medicine?

One of the fascinating and interesting things about these studies, according to Boehnke, is you get to learn a lot about people. “It’s difficult to do a lot of experimental work giving people cannabis, especially if you want to give them a product similar to what you might get in a dispensary,” he said. “A lot of what I work with is people’s subjective responses and reports about using cannabis, which tells you a lot about the use experience and the culture. Working with the folks at the dispensaries also gave me a cool and unique lens into that aspect as well.

“These studies have changed my ideas about medical cannabis,” he said. “In some ways, they’ve helped contribute to my understanding of what we think of as medicine, as well as how cannabis fits into healthcare.”

Boehnke also pointed out that for too long people have been saying that cannabis is one of two things—it’s either panacea or poison. He believes both of those have been shown to be false, adding that we should find a way to be thoughtful and judicious about taking the middle path between them. "We can do that with science. I think we can do that also by addressing the massive cultural and societal wrongs that have been done with cannabis criminalization," he said. "Because if we just move into treating cannabis as a medicine without acknowledging the massive amounts of pain and suffering inflicted by criminalization, I think we're not doing our duty."

Boehnke shared a plea to physicians and healthcare professionals. "Many healthcare professionals worry that we don't know what we're doing because cannabis is so different. But every time a patient starts a new medication, you're embarking on an N=1 experiment. The patient may respond positively or they might not. But you figure that out together using joint decision making and through trying to address that individual's personal needs and preferences," he said. "I believe thinking about cannabis in that context can be very instructive
and useful."

Future Research

Boehnke and his colleagues recently received funding from the National Institutes of Health (NIH) to better understand how CBD and THC interact with different types of chronic pain as well as with sleep in the context of chronic pain. Boehnke's goal is to figure out how CBD and THC act together or separate so that they can then translate that information back to the patient. "From there, we hope to be able to say if you have these types of symptoms, perhaps you should be using CBD, THC, a combination, or whatever the case may be," he said.

In that study, Boehnke and his colleagues will be recruiting people, giving them CBD, THC, or the combination, and doing a wide range of assessments with everything from neuroimaging to quantitative sensory testing—which is a way of testing people’s sensory function, such as pain thresholds. They will also be looking at how inflammatory biomarkers change after a course of a controlled cannabinoid treatment.

"I'm definitely interested in trying to better understand the role of CBD, either by itself or with lower THC doses. I think that that's an important place to target because I think some people will respond to CBD alone, but a lot will likely require a bit of THC," he said. "So figuring out how to do that in a thoughtful way that translates very well to clinical practiceis important."

"I think it's also important to frame our findings in terms of mitigating opioid overuse. For example, we know that people use CBD, they use cannabis as an opioid substitute, but how do they specifically do that? Do they use a CBD product? Do they use a THC product? Do they use a combo? Is it so individualized that there's no point in coming up with a protocol? I think these are all open questions that would be really interesting to try to figure out moving forward.

"It would also be great for the medical cannabis industry to move in a direction that supports these open questions. I've heard many concerns from physicians and scientists that this industry is making a huge amount of money selling cannabis products, but that they aren't actually testing whether these products are safe and effective. Supporting research efforts would both improve that image and also help integrate medical cannabis into existing healthcare."

Only time will tell if Boehnke's research can encourage a thoughtful integration of cannabis into the medical system.

References

1. https://www.cdc.gov/drugoverdose/epidemic/index.html.
2. E.K. Choo, S.W. Feldstein Ewing, and T.I. Lovejoy, “Opioids Out, Cannabis in Negotiating the Unknowns in Patient Care for Chronic Pain” JAMA 316(17), 1763–64 (2016).
3. K.F Boehnke, E. Litinas, and D.J Clauw, “Medical Cannabis Use Is
   Associated with Decreased Opiate Medication Use in a Retrospective
   Cross-Sectional Survey of Patients with Chronic Pain” J. Pain 17(6),
   739-44 (2016).
4. K.F Boehnke, J.R. Scott, and E. Litinas, et al., “Pills to Pot: Observational Analyses of Cannabis Substitution Among Medical Cannabis Users with Chronic Pain” J. Pain 20(7), 830-841 (2019).
5. K.F Boehnke, J.R. Scott, and E. Litinas, et al., “High-Frequency Medical Cannabis Use Is Associated with Worse Pain Among Individuals with Chronic Pain” J, Pain 21(5-6), 570-58 (2020).
6. K.F. Boehnke, S. Gangopadhyay, and D.J. Clauw, et al., “Qualifying Conditions of Medical Cannabis License Holders In The United States” Pharm Med Tech. 38(2), 295-302 (2019).

Read this article in Cannabis Patient Care's March/April 2021 digital edition.