Cannabis and the Digestive System: What the Endocannabinoid System Does in Your Gut

Cannabis works on your digestive system through the endocannabinoid system, a network of receptors that runs from your esophagus all the way down to your colon. THC and CBD can influence appetite, how fast food moves through your gut, stomach acid and how you feel pain, which is why weed helps some people's digestion and wrecks others'.

Cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD) bind to receptors of the endocannabinoid system, which you'll find all over the body, gut included. That's how they can nudge things like hunger, intestinal motility (the muscle movements that push food along), gastric secretion and pain perception, among other functions.

How scientists found the endocannabinoid system in the gut

The number one job of the gastrointestinal (GI) system is digesting food. Through a carefully choreographed series of steps along the GI tract, what you eat gets turned into the energy your body needs to keep everything running. It's one of the fundamentals of animal biology, and the endocannabinoid system (ECS) is deeply involved in regulating the whole process.

The first discoveries of the ECS in the digestive tract

The first report of the ECS in the mammalian gut goes back to 1995, when a team of Israeli scientists led by Raphael Mechoulam, the chemist who first identified THC, isolated an endocannabinoid called 2-arachidonoylglycerol (2-AG) from a dog's intestine.

Another endocannabinoid, anandamide, was later identified in the mouse intestine. After that, researchers found pieces of the ECS in every single section of the mammalian GI tract.

Where cannabinoid receptors sit in the digestive system

CB1 receptors show up practically everywhere, especially in the stomach and the colon, the last stretch of the intestine. There they live mostly in epithelial cells, the cells that line the gut wall. CB1 receptors are also found on the neurons that run the GI tract, particularly those of the enteric nervous system, often called the "second brain" in your gut.

CB2 receptors also turn up in the enteric nervous system, but they're mainly found on immune cells throughout the GI tract.

The enzymes that build and break down endocannabinoids have been found along the entire digestive tract too. The gut is also home to palmitoylethanolamide (PEA), oleoylethanolamide (OEA) and other related compounds.

These molecules don't hit CB1 or CB2 receptors directly, but they behave a lot like endocannabinoids and play an important role in the GI system, especially when it comes to keeping inflammation in check.

The endocannabinoid system and gut balance (homeostasis)

Can THC help with acid reflux?

After you chew, food travels down the esophagus and into the stomach through the esophageal sphincter. When that sphincter relaxes at the wrong time, you get gastroesophageal reflux, aka acid reflux, a condition that hits roughly 20% of adults in Western countries at least once a month.

In a 2009 clinical study, taking 10 or 20 milligrams of THC reduced those sphincter relaxations and, with them, the number of reflux episodes. Animal experiments suggest this effect comes mainly from activating CB1 receptors.

Does cannabis protect the stomach lining?

Once food lands in the stomach, hydrochloric acid secreted by cells in the stomach wall breaks it down even further. When your stomach pumps out too much of that acid, you get heartburn, and in serious cases that can lead to gastritis or ulcers (damage to the stomach wall).

Even before cannabinoid receptors were identified, researchers noticed that giving THC to rats with ulcers caused by anti-inflammatory drugs reduced gastric secretion and how badly the ulcers formed, which points to a protective effect of cannabinoids on the stomach.

And the ECS doesn't only guard against drug-induced ulcers. In 2003, researchers found that activating the CB1 receptor could reduce the gastric secretion triggered by cholera toxin.

Cannabis and how fast your stomach empties

Activating CB1 receptors in the stomach can also slow down gastric emptying, which matters a lot for gastroparesis, a chronic condition where the stomach is partially paralyzed.

In people with gastroparesis, the stomach empties more slowly than it should, which can cause loss of appetite, nausea and vomiting. There's currently no specific cure, but drugs that block the action of cannabinoids could turn out to be a useful strategy.

How weed affects gut motility

From the stomach, food has to travel the entire length of the intestine so nutrients can be absorbed and waste can be pushed out. That happens through peristalsis, a wave of contractions and relaxations in the gut wall that moves food from the duodenum toward the colon.

One motility problem is hypermotility, when things move too fast, which can lead to poor absorption and conditions like irritable bowel syndrome (IBS). Gut motility is directly controlled by the enteric nervous system, a network of neurons that runs on its own and is also regulated by the ECS.

Back in 1978, researchers showed that THC could reduce intestinal motility in guinea pigs. Thirty years later, studies showed that cannabidiol (CBD), a non-intoxicating cannabinoid, could also calm inflammation-driven intestinal hypermotility.

These plant cannabinoids, along with endocannabinoids and synthetic cannabinoids, act mainly by stimulating CB1 receptors in the enteric nervous system. Once switched on, CB1 cuts the release of acetylcholine (a neurotransmitter) from the gut's nerves, which means weaker intestinal contractions and slower motility.

No surprise, then, that the "Handbook of Experimental Pharmacology", one of the most respected references in the field, calls CB1 receptors the physiological "brakes" of the GI system.

The downside: how heavy cannabis use can hurt your digestive system

Cannabinoid hyperemesis syndrome (CHS)

Cannabinoid hyperemesis syndrome (CHS) is a condition that causes cycles of vomiting and a compulsive urge to take hot showers or baths to ease the nausea and the need to throw up. It usually shows up in people who've used a lot of cannabis for many years.

People with CHS typically end up seeking medical care for intense vomiting and nausea after a long stretch of heavy, daily use. Case studies have led researchers to conclude that cannabis is what's causing it.

Although it's a controversial and under-researched condition, there are more than two dozen case reports pointing to cannabis as the main cause. Most of them haven't explained the mechanism behind this paradoxical side effect of long-term, heavy use.

That said, at least one study has suggested CHS may come from THC's effect on gut motility, which could lead to delayed gastric emptying.

Cannabis-induced acute pancreatitis

Beyond CHS, cannabis has also been linked to a handful of acute pancreatitis cases, although the connection is weak and most of the case reports involve people who had also been heavy tobacco smokers for years.

There are roughly 18 reports of people with acute pancreatitis (inflammation of the pancreas) where doctors concluded the condition was ultimately caused by heavy cannabis use in the period before they sought treatment.

In one case, a patient was monitored for several weeks, and his condition got worse every time he smoked the weed his friends were secretly sneaking into the hospital.

It looks like cannabis plays at least some role in triggering acute pancreatitis. But it's also possible these people had a pre-existing condition that cannabis made worse, or that the effect depends on the dose or on other signaling molecules.

What research says about anandamide and pancreatitis

A recent study on anandamide levels in pancreatitis found that anandamide can either reduce or increase how severe pancreatitis gets, depending on whether it's given before or after caerulein.

Caerulein is a decapeptide (a chain of ten amino acids) known to affect gut motility and fluid secretion, and it's also used to induce pancreatitis in lab animals.

Bottom line: what weed does to your digestive organs

Cannabis has several potential benefits for digestion, but it can also cause problems in the GI tract, especially for chronic users. Conditions like cannabinoid hyperemesis syndrome and acute pancreatitis have been linked to long-term, heavy cannabis use.

If you use cannabis regularly and over long periods, it's worth knowing these side effects exist, and talking to a healthcare professional if you notice symptoms that worry you.