In 2019, 17.5% of the American population used cannabis in the past year—up from 11.0% in 2002 (www.samhsa.gov/data/release/2019-national-survey-drug-use-and-health-nsduh-releases). As more states legalize cannabis for medical or recreational use, it’s becoming more common for our patients to add medical marijuana to their medication regimen for various purported indications. In this primer, we will synthesize the debate surrounding the use of medical marijuana for a variety of syndromes, with a focus on pain.

Just to review some basics, cannabinoids can be classified into three groups, according to the National Institute on Drug Abuse:

• Phytocannabinoids: naturally occurring, derived from flora (eg, THC, CBD)


• Endocannabinoids: produced endo­genously (eg, anandamide, 2-AG)


• Synthetic cannabinoids: created artificially (eg, dronabinol, nabilone)

Of the hundreds of cannabinoids that have been isolated and identified, the most commonly known are the phytocannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive component of cannabis.

Medical uses approved by agencies
There are currently only a handful of medical conditions for which cannabis products have been approved by federal agencies in the US and Canada: AIDS-related anorexia, chemotherapy-induced nausea, seizures, and multiple sclerosis. Here are the specifics of these products and indications:

• Dronabinol (Marinol capsules and Syndros oral solution): This synthetic form of THC is approved for the treatment of refractory chemotherapy-associated nausea and vomiting, as well as anorexia associated with weight loss in patients with AIDS.


• Cannabidiol (Epidiolex): This synthetic form of CBD is approved for the treatment of three rare and severe forms of epilepsy: Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex.

Additionally, Sativex (a combination of plant-derived THC and CBD in slightly more than a 1:1 ratio) is approved in Canada and Europe for the treatment of neuropathic symptoms associated with multiple sclerosis, but it is not yet FDA approved or available in the US.

Treatment of non-cancer pain
Cannabis may be effective for treating chronic non-cancer pain. In 2017, the National Academies of Sciences, Engineering, and Medicine concluded that there is “evidence to support that patients who were treated with cannabis or cannabinoids were more likely to experience a significant reduction in pain symptoms,” adding that there was “substantial evidence” that short-term use of man-made oral cannabinoids improves multiple sclerosis–related muscle spasms (www.tinyurl.com/j9nr9vy).

Treatment of opioid use disorder
Observational studies have suggested that where medical marijuana is legal, there is less opioid prescribing—though these are correlational data and do not necessarily imply that legalizing marijuana causes less opioid use. The correlational evidence of the association between cannabis legalization and overdose reductions is clear from several studies (Bachhuber MA et al, JAMA Internal Medicine 2014;174(10):1668–1673). However, there is also evidence that cannabis use increases the risk of developing opioid use disorder (Olfson M et al, Am J Psychiatry 2018;175(1):47–53).

American Society of Addiction Medicine (ASAM) policy statement
According to a policy statement from ASAM released in October 2020, there is a “lack of sufficient scientific evidence” for the effectiveness of cannabis as a medication for many indications approved by states (www.tinyurl.com/y5nx4wt7). ASAM emphasizes the association between using cannabis and the onset of psychiatric disorders, especially psychosis.

Side effects
When working with patients who use marijuana recreationally or for treatment of symptoms, clinicians should be aware of potential adverse effects. We spoke with Benjamin Caplan, MD, a physician with a specialty in treating chronic pain. “I warn patients of a variety of potential side effects, including light-headedness, upset stomach, and occasional strong urges to rest or seclude oneself from outside stimulation,” said Caplan. “It’s not uncommon for cannabis to bring about novel, often pleasant physical sensations, like extreme muscle relaxation, or interesting thought patterns, such as distracted thinking or wildly creative thought, that occur with some of the cannabis varieties.”

As for panic attacks, these usually occur when patients have mistakenly taken too high a dose. This is often because the patient is using an old product that has resettled, with all of the active ingredients at the bottom. Once they shake the bottle, they are usually OK.

One reality: Insurance doesn’t pay for medical marijuana. In some places it does help cover physician visits, said Caplan. In Massachusetts, the dispensaries pay back the cost of the medical visits in free product credits, he said.

NIH and research
The National Institutes of Health (NIH) have started providing formal grants for preclinical and basic researchers to start doing studies on medical cannabis, said Mikhail Kogan, MD, medical director of the George Washington Center for Integrative Medicine and associate professor of medicine at George Washington University. Kogan has treated more than 3,000 patients with cannabis. “Some of the studies involve synthetics, but there’s also beginning to be research in botanicals,” Kogan told Carlat.

The difference between cannabis and dronabinol (synthetic THC) is that cannabis can be more easily titrated, starting with a subtherapeutic dose. Clinicians know that this dose won’t relieve the pain immediately, but at least the side effects are minimal. After waiting a few days, once the side effects decrease and the body adjusts, the dose can be increased. Clinicians will know they’ve arrived at the right dose when there is efficacy and no side effects.

Kogan’s interest in cannabis for pain stems from the fact that his practice is mainly geriatric and palliative (although he tends to use opioids, not cannabis, in palliative care). “In geriatrics, I use cannabis as first-line treatment for a number of conditions.” He also likes cannabis because it is less toxic than ibuprofen or acetaminophen. It also treats many problems that co-occur, especially in older adults. “I can use one plant for chronic pain, insomnia, anxiety, and nausea,” said Kogan. “And I feel strongly that older adults should be the first target” for medical cannabis.

CATR Verdict: Cannabis, while still illegal in the federal arena even for medical use, is legal in many states for medical and recreational use. Physicians may increasingly work with patients using medical marijuana to manage symptoms, and should be aware of formulations, patterns of use, and adverse effects. While some data support the use of cannabis for various conditions, the data are limited regarding its use in chronic conditions such as pain or substance use disorders, and most medical societies agree that more data are needed prior to recommending it for such conditions. For additional resources, see: www.fsmb.org/siteassets/advocacy/policies/model-guidelines-for-the-recommendation-of-marijuana-in-patient-care.pdf; www.cedclinic.com