Endocannabinoids and Digestive Health

Marijuana may have a storied ability to trigger the “munchies,” but its relationship with the gastrointestinal system is much more complex than that. In fact, cannabis has a long history of use for symptoms like abdominal pain, diarrhea, nausea and vomiting.

And it remains highly popular to this day: Surveys have found that as many as two-thirds of adults with inflammatory bowel disease (IBD) have tried cannabis–mainly to counter pain, diarrhea and weight loss.

IBD is an umbrella term for ulcerative colitis and Crohn’s disease–two conditions in which the immune system mistakenly attacks the lining of the digestive tract, leading to chronic inflammation and tissue damage. About 3 million Americans have IBD, according to the Centers for Disease Control and Prevention.

The evidence to support cannabis as a remedy for IBD or other gastrointestinal disorders is still limited. However, a growing body of research is illuminating just how much our digestive health is influenced by the body’s own cannabis-like compounds.

Brain-Gut Highway

Why would medical marijuana have a role in treating GI symptoms? The answer begins in the so-called “brain-gut” connection, a line of communication between the brain and the enteric nervous system that operates in the digestive tract—what researchers have dubbed the body’s “second brain.”

It has long been known that the brain sends signals to the gut. (Think about the “butterfly” feeling you get when you’re nervous.) But recent research has revealed that it’s a two-way street: Gut bacteria, for example, have been shown to influence brain activity and behavior in lab animals.

And it turns out that the body’s endocannabinoid system (ECS) has an important role in all of that brain-gut interplay.

The ECS is different from body systems with a clear structure, like the blood vessels or central nervous system. It consists of naturally made cannabinoid chemicals that activate particular receptors on the surface of cells. Those receptors are dispersed throughout the body, including the brain, the immune system, the bones and skin, and the GI tract. The ECS also features enzymes that either help produce or break down cannabinoids.

When people inhale or ingest cannabinoids from marijuana, those chemicals produce their effects by interacting with the ECS.

The ECS serves a broad and vital function: keeping the body in equilibrium. It helps regulate functions as diverse as appetite and metabolism, stress responses, inflammation, mood and pain sensation.

In the gut, the ECS helps quiet inflammation, regulate pain sensation and slow down the contractions that move food through the digestive system. In theory, that might explain why some people with IBD find that marijuana eases abdominal pain and diarrhea.

In addition, many people with digestive disorders know that psychological stress exacerbates symptoms like abdominal pain—and lab research indicates that the ECS may be the bridge between the brain and the gut in this scenario. For example, stress can rev up lab animals’ sensitivity to pain, but that tendency can be reduced with inhibitors that slow the breakdown of certain endocannabinoids.

All of this has raised the question of whether dysfunction in the ECS might be one reason people develop IBD or other digestive disorders, including irritable bowel syndrome (IBS).

IBS, which affects about 40 million Americans, causes symptoms like pain, cramping, and diarrhea or constipation. [REF 10]

There are hints that the body’s endocannabinoid system could be involved in IBS. In animals, researchers have found, ECS development is affected by early-life stress—which also happens to be a risk factor for IBS in humans.

In addition, people with IBS have been found to carry particular variants in genes that regulate certain ECS receptors and enzymes. Those genes are also associated with contractions and sensation in the gut.

The fact that the ECS helps control inflammation is, of course, a key area of interest: Could problems in that critical duty make people more vulnerable to IBD? That’s far from clear, but research in mice shows that raising endocannabinoid levels can prevent the development of IBD-like disease.

As with IBS, studies have also found hints of a genetic connection between the ECS and IBD. In one study of children with IBD, those with a gene variant that reduces the anti-inflammatory effect of the ECS tended to have more-severe symptoms.

However, other studies have failed to uncover any genetic links. Much more work is needed in this area to understand the complex ways in which a dysfunctional ECS might contribute to digestive disorders.

Can Cannabinoids Treat GI Woes?

While lab findings are necessary and important, the ultimate question is whether medical marijuana or cannabinoids like CBD can actually help patients. A 2019 study of adults with Crohn’s found that cannabis users were less likely than non-users to have a history of complications — including fistulas and abscesses (forms of tissue damage) in the digestive tract. But those types of studies don’t prove cause-and-effect.

That kind of proof comes from clinical trials, which would directly test cannabis products for easing digestive symptoms. Unfortunately, few have been done at this point.

A 2018 review by the Cochrane research network was able to dig up only three clinical trials of Crohn’s patients, involving a total of 93 people followed for eight weeks.

One trial tested marijuana cigarettes against “placebo cigarettes.” The other two tested CBD oil against a placebo (such as olive oil); in one, the oil also contained THC.

None of the trials found that cannabis products improved symptom remission rates. However, patients in the marijuana study and one CBD study did report bigger improvements in either their symptoms or quality of life.

In a separate review of ulcerative colitis trials, the Cochrane group found a similar pattern: Their search turned up two trials that included 92 participants in all. One tested marijuana cigarettes against a placebo, the other used CBD oil containing THC. Neither found that the “real” treatments improved remission rates over eight to 10 weeks. But again, patients on cannabis reported either greater symptom improvements or gains in quality of life.

Overall, the most common cannabis side effects included dizziness, nausea, headache and fatigue.

More recently, researchers conducted the largest trial to date of cannabis for ulcerative colitis: It involved 60 patients who were randomly assigned to take either a “CBD-rich” botanical extract or placebo capsules. Again, there were no difference in remission rates, but the CBD group generally saw their symptoms ease to a greater degree.

The bottom line

As it stands, there are tantalizing clues that medical marijuana or CBD could help ease IBD. But that’s based on small, short-term studies. It’s unknown whether cannabis products can help with IBS or other specific digestive disorders. Clearly, there is a big research gap to be filled.

Right now, 34 states and Washington, D.C. have medical marijuana/cannabis programs. Many either authorize it for specific GI conditions, like Crohn’s disease, or for symptoms that can be caused digestive disorders, such as nausea or chronic pain.

So depending on where you live, cannabis might be an option if you need additional relief for your symptoms. Talk to your doctor about the pros and cons.

About the author

Amy Norton is a freelance journalist and yoga teacher. She was a staff writer and editor for Physician’s Weekly, Medical Tribune and Reuters Health, and has written on health and medicine for MSNBC, The Scientist, Prevention and other publications.