Cannabis-based products may control chronic pain as effectively as opioids, but adverse effects are common, and long-term safety remains unknown, according to a new study.
Several other systematic reviews have recently evaluated cannabinoids for treating chronic pain, but the new study’s methodology was “distinct” in “important ways,” leading to “conclusions that differ from other reviews,” according to the authors of the paper published in the Annals of Internal Medicine.
In the new systematic review, synthetic products with high THC:CBD ratios were associated with moderate improvements in pain, whereas plant-based products with comparable THC:CBD ratios offered for less relief, said study author Marian S. McDonagh, PharmD, professor of medical informatics and clinical epidemiology, and codirector of the Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues.
Specifically, the investigators stratified cannabis-based interventions according to relative content of two key cannabinoids: THC and CBD. Products were sorted into five categories: high THC:CBD ratio (at least 2:1), comparable THC:CBD ratio (less than 2:1 but more than 1:2), low THC:CBD ratio (no more than 1: 2), whole-plant cannabis products, and other cannabinoids.
“In preclinical studies, THC and related compounds have demonstrated analgesic properties, although its potential psychoactive effects and addiction may limit its suitability as an analgesic,” the investigators wrote. “CBD and other cannabinoids may also have some analgesic or anti-inﬂammatory properties and are not believed to be psychoactive or addictive. Given the variation in analgesic effect with THC and CBD, response may differ according to the ratio of THC to CBD in the products used to treat pain.”
The final analysis included 18 randomized placebo-controlled trials involving 1,740 individuals and 7 cohort studies involving 13,095 individuals. Most of the studies were short-term, lasting 1-6 months.
Pain was scored on a ten-point scale, with improvements reported as the mean difference from baseline to post treatment. A mean difference in pain score of 0.5-1.0 was considered a “small effect,” an improvement of 1-2 points was considered a “moderate effect,” and an improvement greater than 2 points was considered a “large effect.”
Cannabis-Based Products With Relatively High THC: CBD Ratios Showed Efficacy
Synthetic products with high THC:CBD ratios offered moderate pain relief, based on a mean difference in pain score of -1.15 (95% confidence interval, -1.99 to -0.54), whereas products with comparable THC:CBD ratios were associated with a small effect on pain, with a mean difference of -0.52 (95% CI, -0.95 to -0.19).
According to McDonagh, treatment response rates were on par with response rates for more conventional treatments, “such as opioids or specific antidepressant drugs,” but data for the cannabis-based products are weaker.
“The amount of evidence available for cannabis-related products is very limited for [response rates]and therefore less certain,” McDonagh said in an interview. “The average reduction in pain severity is also similar to some other treatments, but we do not have studies directly comparing these treatments to draw conclusions.”
The cannabis-based products with relatively high and comparable THC:CBD ratios showed efficacy, they were also associated with “moderate to large increased risk for dizziness, sedation, and nausea,” the investigators wrote, noting that evidence was insufficient to characterize other “key adverse event outcomes” that may occur with long-term use, such as “psychosis, cannabis use disorder, and cognitive deﬁcits.”
For products with low THC:CBD ratios, or without reported THC:CBD ratios, data were too scarce to reach any conclusions at all about safety or efficacy, highlighting the sizable knowledge gaps that remain in the area, the authors said.
“The current evidence on cannabis-related products for chronic pain is quite limited,” McDonagh said in an interview. “Patients with chronic pain should consult with their doctor to discuss which of the many options for treating chronic pain is best for them to start with.”
Patients May Face Resistance When Asking About Cannabis
According to Kevin F. Boehnke, PhD, and Daniel J. Clauw, MD, of the anesthesiology department and Chronic Pain and Fatigue Research Center at the University of Michigan, Ann Arbor, patients with chronic pain may face resistance, or even risk of being reported, when asking about cannabis-based products.
“Some physicians cite lack of data as rationale for not engaging with patients who wish to use or currently use cannabis,” Boehnke and Clauw wrote in an accompanying editorial. “Such practices may reflect consideration of cannabis only as a drug of misuse (even in the 37 states where medical cannabis is legal) and requirements to refer patients who disclose or test positive for cannabis use to addiction services or decline to refill opioid prescriptions.”
Instead of shutting patients out, Boehnke and Clauw suggested clinicians engage in an “open information exchange” with their patients that focuses on “pragmatism, patient experience, known cannabinoid effects, and harm reduction.” In these conversations, the editorialists recommend noting that, “as with other analgesics, some persons will benefit, and others will not.”
They also offered some practical guidance: “Clinicians could suggest using tinctures (effect onset, 15-45 minutes) for breakthrough pain and edibles or capsules (which last about 6-8 hours) for extended relief. … The scientific literature suggests that CBD doses could start at 5-10 mg twice daily and increase to 40-50 mg daily, whereas THC doses could start at 0.5-3 mg (initially at night) and increase to 30-40 mg/day.”
David Copenhaver, MD, MPH, clinical professor and chief of the division of pain medicine at UC Davis Health, Sacramento, shared a similar clinical mindset for patients choosing between opioids and cannabis-based products, specifically, CBD.
Compared with opioids, “the side-effect profile for CBD is less and the risk of mortality is less,” Copenhaver said in an interview, pointing out that nobody, to his knowledge, has ever died from an overdose of cannabis alone, and that CBD doses up to 1,000 mg/kg have been safely tolerated in people. “You present that, and most patients will say, ‘You know, I’d like to give this a try.’ “
If so, Copenhaver makes sure patients know about a nonmedical risk: “The risk to the pocketbook.” Unlike opioids, which are covered under most insurance policies, most cannabis-based therapies are self-pay.
Buyers may get what they pay for, Copenhaver said, since products vary in quality, as do the dispensaries, from “very modest,” to highly sophisticated, with some even using chromatographic datasets to support the purity of their products.
Copenhaver steers his patients toward these more sophisticated retailers. Their expertise appears to be paying off, he said, not only in relief for patients, but also in market share. “Survival of the most fit will occur in the marketplace based on the results,” he said. “Unfortunately, some of that information doesn’t get percolated out into the literature.”
For investigators to fully uncover what cannabis-based products can do for pain, Copenhaver said they need to get as “granular” as the leading dispensaries, which may first require recognition of the “very expansive opportunity” that less-studied cannabinoids may provide .
The study was supported by the Agency for Healthcare Research and Quality, US Department of Health & Human Services. The investigators, Boehnke, Clauw, and Copenhaver, disclosed no conflicts of interest.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.