A guest column by the American Society of Anesthesiologists, exclusive to KevinMD.com.

Marijuana is made from the dried flowers of the cannabis plant. Made of more than 500 chemicals, including over 100 compounds called cannabinoids, the primary active compounds in the plant are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC acts on specific brain cell receptors that react to natural chemicals that play a role in normal brain development and function.  These natural chemicals impact the formation of brain circuits that are important for decision making, mood and responding to stress. THC is primarily responsible for the “high” associated with marijuana use and for other mental health effects such as altered senses (seeing bright colors); altered mood, including hallucinations; and even psychoses at higher doses.

Uncertain composition

Most marijuana is of uncertain composition and purity with significant variations found in the amount of THC and/or CBD contained within. One study found that among CBD products purchased online, a wide range of CBD concentrations existed. This finding is consistent with the fact that there are currently no official dosage recommendations. Further, 26% of tested products contained less CBD than labeled, which could negate any potential clinical therapeutic response. This over-labeling is similar to a 2015-2016 U.S. Food and Drug Administration (FDA) analysis, which found products from 14 companies contained negligible or less than 1% of the labeled CBD content. Additionally, the amount of THC in marijuana has been increasing steadily in recent decades. In fact, the THC concentration in commonly cultivated marijuana plants has increased three-fold between 1995 and 2014 (4% and 12% respectively).

Potential medical use

Of medical interest, THC has been suggested to increase appetite, reduce nausea, and may also decrease pain, inflammation, and muscle control. CBD may also be useful in reducing pain and inflammation, controlling epileptic seizures, and possibly even treating mental illness. Recent animal studies have shown that marijuana extracts may help kill certain cancer cells and reduce the size of others, such as in pancreatic cancer and for a form of brain cancer. The FDA approved a CBD-based liquid medication for the treatment of two forms of severe childhood epilepsy, Dravet syndrome, and Lennox-Gastaut syndrome. Additionally, two FDA-approved drugs, dronabinol, and nabilone, contain THC. They treat nausea caused by chemotherapy and increase appetite in patients with extreme weight loss caused by AIDS. In Europe, nabiximols (Sativex^®), a mouth spray containing THC and CBD, is available to treat muscle control problems caused by multiple sclerosis, but it is not FDA-approved in the United States.

Need for more research

While marijuana use has been legalized in 33 states, Washington D.C., and Puerto Rico, it continues to be a Schedule I substance at the federal level, classified as having no medical use and a high potential for abuse. This has led to limitations on research conducted on marijuana.

Specifically, research related to the benefits and risks of marijuana for pain management is limited. There have been studies associating marijuana access and use with lower opioid overdose deaths. However, a 2019 analysis found opioid overdose mortality rates between 1999-2010 in states allowing medical marijuana use were 21% lower than expected. But when the analysis was extended through 2017, they found that the trend reversed, so states with medical cannabis laws experienced an opioid overdose mortality rate 22.7% higher than expected. The investigators uncovered no evidence that either broader cannabis laws (those allowing recreational use) or more restrictive laws (those only permitting the use of marijuana with low THC concentrations) were associated with changes in opioid overdose mortality rates.

A bipartisan bill titled the Medical Marijuana Research Act of 2019 was recently introduced to amend the Controlled Substance Act, allowing faster approvals for medical marijuana research. This bill along with another, the Cannabidiol Research Expansion Act, seek to expand research on marijuana and its compounds.

Long-term effects

When people begin using marijuana as teenagers, the drug may impair thinking, memory, and learning functions. People who begin using marijuana before age 18 are four to seven times more likely than adults to develop a marijuana use disorder. Repeated exposure to THC at a young age can result in the use of other addictive substances (i.e., nicotine, morphine) and an increase in addiction-like behavior. This has led to a warning from the U.S. Surgeon General’s office on marijuana use and the developing brain, advising caution in adolescents and youth, as well as pregnant and breastfeeding women.

Concerning trends

In a recent survey by the American Society of Anesthesiologists (ASA) of 1,005 adults in the U.S., patients were asked about their personal use of medical marijuana for the treatment of pain. Seventy-five percent of respondents stated they were interested in or have used marijuana or marijuana products for pain management and more than half (62%) believe marijuana and cannabinoids are safer than other pain medications, including opioids.

Along with this belief, 34% of respondents stated they do not feel it is necessary to discuss marijuana/cannabinoid use with their physicians, despite their medicinal use of the drug. The survey also reported a significant proportion of patients believe commercially-sold marijuana and marijuana products are approved by the FDA, a belief more popular among younger consumers.

Patients seeking strategies to alleviate their pain need to know there are many different options, other than marijuana, to treat pain. In fact, it has been clearly demonstrated that no single medication can be safe and effective to manage chronic pain. The most effective option is a multimodal approach that incorporates medications, interventions for pain relief such as injections, stimulators, etc., and complementary techniques such as physical therapy or acupuncture.

Given the risks of interactions with other medications and the long-term effects of marijuana use, it is very important for patients to discuss use with their physician. Patients should ask their physician anesthesiologist for a personalized pain treatment plan that incorporates the latest evidence.

Padma Gulur is an anesthesiologist. Amanda Nelli is a post-doctoral researcher.

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