An estimated 20 million Americans suffer from chronic digestive diseases and disorders. The list includes irritable bowel syndrome, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), celiac disease (the body’s difficulty digesting gluten, a protein found in wheat, rye, and barley), lactose intolerance (trouble digesting the sugar in milk), and “leaky gut,” where the gut’s lining becomes damaged and cannot properly function. These symptoms can be debilitating: chronic stomach pain, cramping, bloating, constipation, nausea, and diarrhea. And finding relief is a constant struggle.

The gut is as complex and mysterious as the Milky Way. Inside it are billions of bacteria, nerves, and tissues, working alone and together to keep your digestion running smoothly. With such complexity, it’s probably no surprise that treating gut issues is difficult. Remedies are often a matter of trial and error, and even the most successful ones don’t work for everyone.

Enter medical cannabis. Science is now looking at how cannabis may reduce pain and discomfort associated with digestive diseases and disorders. Most current research on gut health is based on people’s responses after taking cannabis: Did their symptoms improve? From this perspective, cannabis helps.

For example, a 2021 study published in the journal PLoS One found that people with mild to moderate ulcerative colitis who consumed cannabis cigarettes for eight weeks reported significant improvement of symptoms compared to those taking a placebo.

“Even though research remains in the initial stages, the results have been encouraging,” says Nicholas DiPatrizio, PhD, associate professor of biomedical sciences at the University of California, Riverside, and director of the school’s new Center for Cannabinoid Research.
These types of studies suggest a thumbs-up to cannabis for helping relieve gut issues. Still, they only show an association, not cause and effect. “Nor is it clear how much cannabis people consistently took and when and if any other variables might explain their reaction,” says DiPatrizio. “People may say cannabis works for their gut problems, and while that’s good news, it’s not nearly enough from a science perspective.”

From that science perspective, the question is not whether it works, but how it works. What mechanisms of cannabis are helping it get to the gut of gut health? The answer most likely lays in the endocannabinoid system.

The Key to the Core

The endocannabinoid system (ECS) comprises a vast network of chemical signals and cellular receptors connected to the nervous system. More research is needed to fully understand this complex system, but what we do know is that it plays a huge role in homeostasis, regulating critical functions such as learning and memory, emotional processing, sleep, temperature control, pain management, inflammatory/immune response, and appetite.

The ECS has two primary types of receptors: CB1, found mostly in the central nervous system (the brain and spinal cord), and CB2, located mostly in the peripheral nervous system (the rest of the body). These receptors can only be stimulated by a specific neurotransmitter called an endocannabinoid. The ECS is activated when endocannabinoids bind to CB1 or CB2 receptors in a process that DiPatrizio compares to “a key opening a lock.”

The cannabis plant, meanwhile, contains its own unique compounds called phytocannabinoids. There are at least 100 types of cannabinoids, each with a distinct molecular structure, the most common and well-known of which is delta-9-tetrahydrocannabinol (THC), the one that causes that trademark intoxicating effect. More interesting to researchers, though, is that THC hijacks the ECS.

“THC interacts with your ECS by binding to CB1 and CB2 receptors, just like endocannabinoids,” says DiPatrizio. “It’s a second key that fits the same lock.”

And it may be just the key that cannabis-gut researchers have been looking for.

Gut Check

So far, research remains in the ground-floor phase, looking at the basic correlations between the ECS and the gut. “In other words, if you remove endocannabinoid binders, does it trigger gut problems?” says DiPatrizio. “If so, then the idea of introducing more of these binders like THC could, in theory, help the gut heal.”

DiPatrizio led a recent study, published in 2022 in the International Journal of Molecular Sciences, that looked at how symptoms of leaky gut caused by obesity affect ECS. The research used mice engineered to be void of CB1 receptors in their intestinal lining, feeding them an obesity-inducing diet high in fats and sugars for eight weeks to examine how leaky their gut became.

These mice had far worse inflammation and compromised gut-barrier function compared to mice with their CB1 receptors intact. The results suggest that CB1 receptors in the gut lining are protective against diet-induced leaky gut. “These types of studies serve as the foundation to next identify if adding THC can activate these receptors when digestive issues exist and help treat them,” says DiPatrizio.

For sufferers of GI illnesses, this research offers plenty of reason to hope. But there are still many questions to explore with THC and gut health. Does THC work for some digestive disorders but not others? Is it possible that THC works for only certain symptoms? Maybe THC is not the only chemical in cannabis that can stimulate CB1 and CB2 receptors. And then there are the questions about appropriate amounts and whether it matters how THC is ingested—inhaled, applied topically, or eaten?

Most research focuses on the CB1 receptors, but other experts, including DiPatrizio, believe CB2 may also play an important role. “These receptors are critical to helping control our immune functioning, and it plays a role in managing intestinal inflammation, and pain in inflammatory bowel conditions,” he says. “Right now, the research approach is still at the preclinical phase in mice, and until we extend these experiments into double-blind placebo studies in humans can we definitively know the answer to these questions.”

One of the problems with medical cannabis is that it’s bound in regulatory red tape, which makes it hard to study. It’s classified as a Schedule I substance because it is still considered a high risk for abuse and lacks sufficient evidence for medical use. Therefore, its use in clinical trials requires a special license issued by the Drug Enforcement Agency and many other approvals from researchers’ own institutions and outside agencies like the FDA. These barriers often discourage researchers and make grant funding difficult.

But the initial steps toward possibly using cannabis to treat gut problems already have been taken. Like the Milky Way, there is still much to explore—and the truth is out there.