Surgery centers treating patients who have been using marijuana or cannabinoids for pain relief or nausea are raising questions about efficacy and side effects.

“When people use cannabinoids for pain, I do believe they seek them out with good intentions,” says Edward Mariano, MD, MAS, professor of anesthesiology, perioperative and pain medicine, Stanford University. “As an anesthesiologist and a physician who focuses on pain management around injury and surgery, I’m for any innovation that will help relieve suffering. The difficulty with recommending these cannabinoid products is we don’t always know what’s in them, and that’s scary from a physician’s perspective.”

There is anecdotal evidence of pain relief benefits from cannabis, says Ivan Urits, MD, pain medicine fellow at Beth Israel Deaconess Medical Center, Harvard Medical School. “I run into a lot of patients who use medical cannabis, and they seem to get good benefit,” he reports.

Moderate- to high-quality research suggests cannabis could relieve cancer- and rheumatoid arthritis-related pain, as well as discomfort brought on by fibromyalgia, says Kathleen Russell, JD, MN, RN, associate director, nursing regulation, National Council of State Boards of Nursing (NCSBN). “It’s not to say [cannabis] won’t help with other pain, but we have no evidence positive or negative,” Russell adds. “We just don’t have [enough] research to say it is effective.”

Urits recently coauthored a scientific paper that describes the new field of pharmaceutical development of cannabinoids, including drugs that target endocannabinoid receptor agonists. One product is nabiximols, an extract from the cannabis plant that has been used for pain therapy related to multiple sclerosis, cancer, and other chronic pain conditions. Another drug is Epidiolex, sold in the United States for the management of refractory epilepsy, which could possibly help with chronic pain.1

“More people are going to be using cannabis-based products, so all physicians should be familiar with what’s out there,” Urits says. “It’s difficult to keep up on these because so much is unregulated.”

When patients ask their doctors about using medical marijuana for pain, physicians must determine if the patient has a qualifying condition that fits into what their state’s legislature approved for medical marijuana use, Russell notes. For example, the state of Illinois lists more than 40 different conditions for using medical marijuana, she adds.

But just because a state approves a list of qualifying conditions for medical marijuana does not mean that cannabis is effective for everything on that list. “These lists are based on anecdotal research and what advocacy groups that come before the state legislature say will help people, as well as based on some research evidence,” Russell explains.

Without evidence-based guidelines and FDA approval of cannabis for use in postsurgery pain, surgeons might not want to include cannabis in any pain management plan. “I would not recommend cannabis over FDA-approved medications,” says Kevin Hill, MD, MHS, director, division of addiction psychiatry, Beth Israel Deaconess Medical Center, and associate professor of psychiatry, Harvard Medical School. “One point I make about cannabis for issues like pain is that it’s a viable alternative, but not a first- or second-line treatment. If a patient has tried multiple medications for pain and injectables for pain, then would you consider cannabis for pain, and a lot of physicians still would not.”

The National Academies of Science, Engineering, and Medicine found conclusive evidence that cannabis helps patients effectively manage chronic pain. One meta-analysis revealed that cannabinoids reduced pain 30% more than placebo.2

Despite some evidence of the pain-relieving qualities, Hill’s paper on medical use of cannabis concluded that evidence is insufficient for the use of medical cannabis for most conditions. Physicians most likely will remain reluctant to recommend it unless the drug is legalized nationally and there are more studies proving its efficacy.2

Hill foresees a future where cannabis is better studied and regulated, and physicians are willing to consider recommending it. “Doctors can have a risk-benefit conversation with patients,” he says.

“Having the awareness that patients are using cannabinoids has to be seen as an opportunity, an open door to having conversations with patients about their suffering and how they think they’re helped by cannabinoids,” Mariano says. “That’s an opportunity to find out if there are other approved therapies that can make a difference, as opposed to their using substances that are not federally regulated.”

Research also is lagging regarding using cannabis to alleviate general nausea symptoms. “Studies have not determined the effectiveness of using marijuana for nausea, in general, but were specific to chemotherapy-induced nausea and vomiting,” Russell says.

The cannabis industry is not waiting for federal legalization to expand. CBD products are sold legally over the counter in many states.3 In the past few years, the CBD market has exploded. Industry projections say it will become a billion-dollar market in 2020, a seven-fold increase from 2016.4

A recent Gallup survey found that 14% of Americans use CBD products, and 40% of respondents using CBD said they use it for pain. Twenty percent said they use CBD for anxiety, and 11% use it for sleep/insomnia.5

CBD is made from cannabis plants, including hemp, which does not contain THC. “The CBD component of the plant is not psychoactive, and it’s popular for a variety of health issues,” observes Doris Gundersen, MD, medical director and psychiatrist, Colorado Physician Health Program in Denver. “It has anti-inflammatory properties and is used topically for rashes; it has sedative properties and is used for sleep.”

Hemp was legalized with the passage of the 2018 Farm Bill, which treats hemp, a crop used to make ropes, textiles, various industrial products, and CBD oils, similarly to other crops. It had been included with marijuana as a Schedule I substance, but this is no longer the case.6

Although some states say CBD use is legal only for certain medical conditions, the substance is sold more widely. For example, in South Carolina, CBD is legal only for severe seizure disorders, yet shops selling CBD oils and products are widespread. The FDA does not regulate these products, and are treated as natural supplements.

From a clinician’s perspective, CBD use is a risk factor because the lack of regulation means little is known about what is in these products, Mariano says. “There was an interesting research letter published in JAMA that looked at online CBD products that you could purchase without a prescription,” he recalls. “They tested more than 80 products to see if they had the ingredients listed on the label.”

Investigators found that only 31% of those products were labeled accurately. Plus, one-fifth of the CBD products contained THC, which is not supposed to be in CBD.7 “This is very scary ... the patients I talk to who use CBD products say they use CBD because they worry about THC side effects,” Mariano says. “It is difficult to remove all the THC from the CBD products, so the public has to be aware of what is in these products,” Gundersen adds.

Physicians who want to answer patients’ questions about the use of these products for pain, nausea, and other symptom relief will find little help in scientific literature. “Right now, we have only naturalistic studies, but not well-designed, placebo-controlled, randomized clinical trials,” Gundersen says.

Some surgery patients use cannabis products for debilitating presurgery pain. Physicians have no way of knowing the quality or potency level of these products as they would if the patient were on FDA-approved pain medication, Mariano notes. For example, a patient might use CBD cream to help with chronic osteoarthritis pain. Another patient might use inhaled marijuana for chronic back pain.

“I’m reluctant to have patients stop using medications that improve their chronic pain,” he adds. “That’s a complicated scenario that you have to take case by case.”

REFERENCES

  1. Urits I, Borchart M, Hasegawa M, et al. An update of current cannabis-based pharmaceuticals in pain medicine. Pain Ther 2019;8:41-51.
  2. Hill KP. Medical use of cannabis in 2019. JAMA 2019; Aug 9. doi: 10.1001/jama.2019.11868. [Epub ahead of print].
  3. Plant People. Is CBD oil legal? A complete guide to state laws in 2019, Aug. 8, 2019. Available at: http://bit.ly/2SjiJt0.
  4. Borchardt D. The cannabis market that could grow 700% by 2020. Forbes, Dec. 12, 2016. Available at: http://bit.ly/2Z9mrHa.
  5. Brenan M. 14% of Americans say they use CBD products. Gallup, Aug. 7, 2019. Available at: http://bit.ly/2MdBL0a.
  6. O’Connell K. Legal hemp in the USA: What the 2018 Farm Bill means for US hemp & agriculture. Ministry of Hemp, Dec. 20, 2018. Available at: http://bit.ly/38VfX37.
  7. Bonn-Miller MO, Loflin MJE, Thomas BF, et al. Labeling accuracy of cannabidiol extracts sold online. JAMA 2017;318:1708-1709.