Review: Cannabinoid Use in the Management of Gastrointestinal Symptoms

A review published in Current Gastroenterology Reports in February 2015 examined the role of cannabinoids in the treatment of gastrointestinal (GI; the system involved in ingestion and digestion of food, and excretion of waste) symptoms like nausea, vomiting, and visceral pain (pain that originates from in/around organs) and found that certain targeted cannabinoid therapies may be useful in GI disease/disorder management.

Background: Cannabinoid Effects on the GI System

The researchers note that modulation of the endocannabinoid system (especially the type of cannabinoid receptor found most frequently in the gastrointestinal system, known as CB1 receptors) may regulate:

• food intake
• nausea and vomiting
• stomach secretion (the cells of the stomach release acid to digest food)
• stomach protection (if the stomach isn’t protected, it can get damaged by the acidic secretions)
• GI motility/movement (too much movement –> diarrhea, too little movement –> constipation)
• ion transport (absorption and secretion –> e.g. maintaining proper fluid/electrolyte [e.g. salt] balance)
• internal organ sensation
• the inflammation process that results from certain GI illnesses
• the number of cells of the GI tract (too many cells may indicate cancer or a disease process, too few may lead to tissue injury)

They also note that modulation of another type of cannabinoid receptor (CB2) which are found most commonly in cells of the immune system (which helps the body recover from, or prevent, sickness/injury) can help:

• regulate motility/movement
• control the inflammation process that results from certain GI illnesses
• in reducing internal pain and sensation

Findings of the Review

Pain

Visceral pain (pain in/around the organs) is caused by over-stretching, lack of blood flow, or a destructive inflammatory process. Individuals often feel the pain in multiple areas and have trouble figuring out exactly where the pain is coming from.

Patients with the GI symptom of visceral pain most commonly have either (1) non-ulcerating stomach pain or (2) irritable bowel syndrome (IBS). Irritable bowel syndrome can cause diarrhea, constipation, gas, and pain, causing a severe decrease in patients’ quality of life, and results in millions of health visits and a cost of billions of dollars every year, so finding safe, effective treatments would provide a wide range of benefits.

Overall, researchers found that in animal studies, cannabinoids stimulated CB1 and CB2 receptors, as well as another receptor known as TRPV1, resulting in:

• pain relief and decreased sensation in the abdomen
• decreased motility (i.e. less movement of the bowel walls –> less diarrhea)
• decreased sensitivity to stretching (wave-like tightening and relaxation of the gut causes digested food to move towards the rectum to be expelled as waste- it can be triggered by stretching of the bowel walls, which happens when the bowels become full- excessive stimulation of this process can result in diarrhea)

Another study, using mice acting as models for humans with GI disorders, found that an agent that stops the action of an enzyme that breaks down the endocannabinoid anandamide (and therefore increases levels of anandamide in the body) was able to prevent excessive movement of the gut wall and reduced pain.

However, in the human studies assessed, two studies found that administration of synthetic, isolated THC either (1) decreased sensitivity to stretching, but did not affect pain sensation or (2) had no effect on sensitivity. However, in a test of function of the esophagus (food travels from the mouth, through the esophagus, and into the stomach), another study found that treatment with THC after the test (but not before) decreased sensitivity to stretching and relieved pain. Also, given the results of the animal studies, it’s possible that other cannabinoids besides THC, or a combination of THC plus other cannabinoids, may be effective in controlling gut wall movement and pain.

Of the pain studies reviewed, side effects were mild and included sleepiness, an increase in awareness of one’s surroundings, light-headedness, and an increase in heart rate.

Nausea and Vomiting

Nausea and vomiting can be caused by diseases/disorders, pregnancy, and motion sickness, or as a side effect of commonly used medications or treatments, such as chemotherapy. It is caused by stimulation of certain areas of the brain that have receptors for the signaling molecules dopamine and serotonin, and cannabinoids (CB1 receptors). Nausea and vomiting can have a severely negative impact on quality of life, especially for people who experience them frequently.

In one study analyzed by the authors, they found that in a test of motion sickness, those individuals who experienced nausea with movement had (1) lower levels of the endocannabinoids 2-AG and anandamide, (2) fewer active CB1 receptors, and (3) increased levels of an endocannabinoid breakdown product, than those who did not experience nausea. This means that an increase in endocannabinoids or cannabinoid receptor stimulation may have been protective against nausea.

Isolated, synthetic THC has been used for cancer patients with chemotherapy-induced nausea and vomiting. In one study, it was found to be more useful than dopamine receptor blockers, and in another it was comparably effective to dopamine receptor blockers when used with another chemotherapy drug that causes vomiting, called cisplatin. Even though the synthetic THC was not more effective, these results are still important given that dopamine antagonists may have serious side effects.

In another study, synthetic THC was similarly effective as serotonin receptor blockers, and even more so when it came to “mild-moderately severe” nausea. Another study of Sativex (a compound with equal parts THC and CBD), demonstrated that the addition of Sativex to an anti-nausea/vomiting treatment helped to prevent nausea and vomiting even more, with few and mild symptoms.

The researchers also recommend further research into agents that activate only CB2 receptors, or CB1/CB2 receptors in areas of the body other than the nervous system, in order to prevent the psychoactive effects of cannabis (those that occur when someone is intoxicated by cannabis, or “high”). However, in some cases, stimulation of receptors that lead to intoxication (or the “high” produced by cannabis with higher concentrations of THC) may be necessary for optimal management.

Conclusion

Given the safety profile of endocannabinoid modulation and phytocannabinoids (i.e. cannabinoids found in cannabis) and the debilitating nature of many GI disorders/diseases, increased research into their management with the use of various cannabinoids is warranted. Increased research will help to determine (1) which GI disorders, diseases, and symptoms cannabinoid therapies may be useful for and (2) what type of cannabinoid therapy is best in each situation.

According to the researchers, “In conclusion, our review suggests that cannabinoids have the potential to play a vital role in the modulation of nausea, vomiting, and possibly visceral pain. Although the jury is still out on determining the “magic drug,” it seems that with the development of newer ligands [agents that bind to receptors, e.g. cannabinoids], the future appears promising.”

For information on reasonable expectations and safety in considering whole-plant medical cannabis use, as well as how you can advocate to move cannabis out of the Schedule I controlled substance classification in order to increase research on phytocannabinoids in the United States, click here.