Chapter 4: Gastrointestinal Health and Disease

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Human Digestive System

The human gastrointestinal tract or more commonly the digestive system is responsible for both the digestion process and nutrition acquirement. To achieve these six main functions occur, ingestion, secretion, mixing, digestion, absorption, and excretion. The gastrointestinal system also includes up to 80% of the body’s immune tissue. This digestive system consists mainly of the digestive tract; a series of structured organs that food and liquids get processed into absorbable forms and delivered to the bloodstream.

The digestive tract begins at the lips; it consists of the mouth or oral cavity that include the teeth tongue and saliva, which create the bolus swallowed matter. The matter goes down the throat, through the esophagus and into the stomach. Most digestion takes place in the small intestine; saliva and gastric juices contain amylase to break down food, which is moved by peristalsis; while in the intestine minerals and nutrients are absorbed.

Further absorption of nutrients and liquids continues in the large intestines colon; this muscular tube connects the rectum to the cecum that links to the small intestine. Leftover waste from the digestive process is passed through through the colon and then emptied into the rectum. The stool is then excreted through the anus.9

In addition to the digestive canal, other essential accessory organs that do not pass food through but are essential in the digestion process. These accessory organs are:

  • Teeth: small hard organs sculptured for grinding and cutting of food.
  • Tongue: another small organ made up of muscle pairs and covered with a thick skin layer containing taste buds. Besides sending taste information to the brain the tongue also pushes the food for swallowing.
  • Salivary glands: there are three sets of salivary glands in the mouth; the produce saliva, a watery secretion that moistens and lubricates food.
  • Liver: the second largest organ in the body, it is the detoxification center; bile production and secretion into the small intestine.
  • Gallbladder: a much smaller organ, located at the back of the liver; it stores and recycles excess bile for reuse in the small intestine.
  • Pancreas: a large gland below the stomach used for secretion of digestive enzymes necessary to complete food digestion in the small intestine.

CBD and Gastrointestinal Health and Disease

In the following section, the relationship between gastrointestinal diseases and CBD will be explained. Many gastrointestinal diseases can be related to oxidative stress these include disorders such as nausea, emesis, GERD, ulcers, irritable bowel syndrome, inflammatory bowel disease, gastric,  small intestinal and colorectal cancers. When there is damage caused by an injury or infection, the human body mounts an active inflammatory response to alleviate that damage. This response is through the release of microglial cells and macrophage. However, this response is associated with the release of Ultimate reactive oxidative species nitric oxide and tumor necrosis Factor all of these cars and escalation of information and deterioration of microvascular and a deficiency of the endocannabinoids.2, 3, 11-13

Nausea and Emesis

Nausea and vomiting or emesis are two critical elements in the protective responses that are used by humans to avoid ingestion or digestion of potentially harmful substances. However, reduced neural mediated responses are at times manifested as symptoms of diseases and are often the side effects of a variety of medications. For very long time cannabis has been known to limit or even prevent nausea and emesis from a variety of causes and this has led to extensive research that has revealed the importance of cannabinoids and their receptors in the regulation of emesis. The discovery of the endocannabinoid system has also led to more knowledge of our regulation of nausea and vomiting and their involvement in the production of endogenous cannabinoids. The cerebral cortex is covered with CB receptors located mostly at its base; specifically, CB1 receptors are associated with nausea and emesis, which can be related to an acquired CECD condition which is induced by infections or iatrogenic processes. Intense and severe chronic emesis is associated with electrolyte imbalance and dehydration and can become life-threatening. Treatment with CBD, based on research has shown that it can indirectly increase the density of circulating cannabinoids that bind to CB1 receptors and thereby modulating nausea and vomiting.3, 5, 11, 13-17

Gastroesophageal Reflux Disease (GERD)

Gastroesophageal reflux disease (GERD), gastric reflux disease or acid reflux disease is described as chronic symptoms or mucosal damage resulting from the abnormal reflux in the esophagus. At the entrance to the stomach there is a valve called esophageal sphincter (LES); as soon as food enters the stomach, the LES should close so that no food or enzymes or bile can splash back up into the esophagus. If it does not close or if it opens often, stomach acids can move into the esophagus and cause heartburns. There are various causes including, eating foods containing high amounts of acid or drinking alcohol. GERD is described as an acquired CECD condition but can also be genetic that impacts CB1 receptors found in the gastrointestinal tract. Studies conclude that the density of circulating endocannabinoids may increase through the medical administration of phytocannabinoids. This will reduce the pressure of the esophageal sphincter, consequently protecting the esophageal mucosa. Hence, the phytocannabinoid CBD is helpful in both the prevention and management of gastroesophageal reflux disease.7, 35, 86, 102-105

Acid reflux, heartburn and gerd infographic with medical illustration

Gastric Ulcer

Peptic ulcers are exposed sores that develop on the inside lining of the stomach (referred to as gastric ulcers) and the upper portion of the small intestine (duodenal ulcers). The symptoms of these ulcers include burning abdominal pain, heartburn, and nausea and in severe cases bleeding.  Peptic ulcers are a result of acids in the digestive tract eating away the inner surface of the stomach; the gastrointestinal tract is coated with a mucous protective layer, however, if acid concentration increase they may be able to penetrate this protection.

A common bacteria, Helicobacter pylori is found in contaminated food and water is also found in the mucous protective layer. Usually, this bacteria is harmless, but it can cause inflammation in the stomach’s inner layer resulting ultimately into ulcers. Although this bacteria is one of the leading causes of gastric ulcers, it is not the only cause. The regular use of specific pain relief medication, such as aspirin, ibuprofen, and Tylenol can irritate and inflame the inner lining of the stomach and small intestine. Peptic ulcers are more common amongst adults that take such medications regularly.

Gastric ulcers are also related to the malfunction of CB receptors in the gastrointestinal tract. An excess of CB receptors is signified by acid-secretion parietal cells; which are a subset of gastric mucosal cells. Researchers have suggested that cannabinoid administration improves the receptivity of CB and increase cannabinoid density, consequently enhancing both CB receptors and acid secretion; both elements are related to alleviating gastric erosions.3, 8, 14, 17, 18, 20, 22, 36

Irritable Bowel Syndrome

Irritable Bowel Syndrome is a common disorder part of several conditions known as functional gastrointestinal disorders. The symptoms of IBS vary but commonly include abdominal pain, bloating, cramping, diarrhea and constipation. Although the exact cause is unknown,  IBS does suggest an underlying clinical endocannabinoid deficiency making it a suitable candidate for treatment with cannabinoid administration. Research has shown that cannabinoids can improve reactive inflammation in the bowel by directly affecting CB2 receptors. Moreover, depression and anxiety are integral in the development of IBS, can also be alleviated by cannabinoids affecting CB1 receptors in the cerebral cortex.20, 23-25

Crohn’s Disease

Crohn’s disease is an inflammatory and autoimmune bowel disease which causes inflammation in the digestive tract. The condition can result in abdominal pain, severe diarrhea, heme positive stool, fatigue, fever, weight loss, and malnutrition. Crohn’s disease can expose any part of the digestive system, but it is concentrated mostly in the colon.

It is a chronic disease correlated with many extraintestinal conditions that include dermatitis, arthritis, ocular inflammation, and liver and pancreas malfunction. Moreover, Crohn’s disease makes the body vulnerable to bowel obstruction and colon cancer.

Research has shown that the therapeutic administration of CBD expedites relaxation of the lower esophageal sphincter and modulation of colonic motility. Central and peripheral CB1 (fundamental to the endocannabinoid system) receptors will also witness and improved cannabinoid interaction, which is crucial in the prevention of nausea and emesis.2, 4, 7, 13, 17, 20, 22

Colon Cancer

Colorectal or colon cancer is preventable and curable if detected early on. This cancer forms tumors in the tissues of the colon and rectum. Symptoms of the condition include constipation, diarrhea, changes in stool shape and colors, nausea, vomiting, and fatigue.

Clinical and in vivo studies both illustrate promising results for the positive effect of CBD eliminating cancer cells. CBD promotes the death of cancer cells through an endoplasmic reticulum stress pathway that stimulates and fosters autophagy and apoptosis. Research indicates that CBD decreases the invasiveness of cancer cells through the stimulation of intracellular adhesion molecules. CBD is a suitable and prospective treatment for the prevention of colorectal colon.6, 13, 16, 17, 20, 22, 26-34

Pancreatic Cancer

Pancreatic cancer usually manifests after the age of 45 but tends to spread silently before being diagnosed. This makes it one of the deadliest cancer diagnoses. There is a variety of exocrine pancreatic cancers such as adenosquamous carcinoma and acinar cell carcinoma yet the most prevalent form is pancreatic adenocarcinoma.

Most symptoms of this pancreatic cancer develop after the disease has progressed and spread, leaving it difficult to treat. These symptoms include jaundice, manifesting in yellowing of the skin and eyes, darkening of urine and light colored stool. Other common symptoms also include back pain, bloating, abdominal pain, nausea, vomiting, loss of appetite and weight.

The results of CBD treatment for pancreatic cancer show promising effects that include the hindering of tumor growth and apoptosis. The formation of reactive oxygen species is also inhibited by CBD treatment, consequently preventing cells from transforming. Scientific research shows that people who have a genetic or acquired risk of pancreatic cancer could avoid this risk through CBD administration.6, 10, 12, 27, 29, 32

Hepatic Cancer

Liver cancer appears first in the cells of the liver. The liver is located in the upper right portion of the abdomen, beneath the diaphragm and above the stomach.

Different types of cancer can form in the liver, the leading liver cancer is a hepatocellular carcinoma, which originates in the primary type of liver cell (hepatocyte). Other much less common types of liver cancer include intrahepatic cholangiocarcinoma and hepatoblastoma.

Hepatocellular carcinoma is the most common variety of primary liver cancer. Hepatocellular carcinoma tends to occur in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. Signs and symptoms include weight and appetite loss, upper abdominal pain, nausea, vomiting, general weakness, fatigue, and jaundice.

Research has shown that the anti-cancer effects of CBD can promote cancer cell death, inhibition of cell proliferation and prevention of tumor angiogenesis. All of which support the use of CBD as a treatment for hepatic cancer.2, 6, 7, 10, 16, 17

Cirrhosis

Cirrhosis emerges when scar tissue replaces normal, healthy tissue in the liver. It happens after the healthy cells are damaged over an extended period, usually several years. The scar tissue causes the liver to become lumpy and hard, ultimately leading to organ failure. The scar tissue hinders blood from getting through the portal vein that goes into the liver.

When blood retreats into the portal vein, it can get into the spleen and cause trouble in that organ, as well. A liver transplant is deemed as the only cure for cirrhosis, but it can also be slowed down by treating whatever is causing it.

Research has shown that the indirect stimulation of CB2 receptors through the administration of CBD reduces portal hypertension, infiltration of inflammatory cells and decreases fibrosis. These findings support the promising role of CBD in the management of cirrhosis. It is worthy to note that in a cirrhotic liver, THC extracted from cannabis may encourage fibrotic scarring, while it has no negative impact on a healthy liver.1, 20, 35

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