Cannabinoids Alleviate Dyspepsia Symptoms

Dyspepsia

Dyspepsia is one of the most common ailments of the bowel (intestines), affecting an estimated twenty percent of persons in the United States.  Perhaps only ten percent of those affected actually seek medical attention for their dyspepsia.  Dyspepsia is not a particularly good term for the ailment since it implies that there is "dyspepsia" or abnormal digestion of food, and this most probably is not the case.  In fact, another common name for dyspepsia is indigestion, which, for the same reason, is no better than the term dyspepsia!  Doctors frequently refer to the condition as non-ulcer dyspepsia.

Dyspepsia (indigestion) is best described as a functional disease.  (Sometimes, it is called functional dyspepsia.)  The concept of functional disease is particularly useful when discussing diseases of the gastrointestinal tract.  The concept applies to the muscular organs of the gastrointestinal tract-esophagus, stomach, small intestine, gallbladder, and colon.  What is meant by the term, functional, is that either the muscles of the organs or the nerves that control the organs are not working normally, or, as a result, the organs do not function normally.

What are the complications of dyspepsia (indigestion)?

The complications of functional diseases of the gastrointestinal tract are relatively limited.  Since symptoms are most often provoked by eating, patients who alter their diets and reduce their intake of calories may lose weight.  However, loss of weight is unusual in functional diseases.  In fact, loss of weight should suggest the presence of non-functional diseases.  Symptoms that awaken patients from sleep also are more likely to be due to non-functional than functional disease.

Most commonly, functional diseases interfere with patients' comfort and daily activities.  Persons who develop nausea or pain after eating may skip breakfast or lunch.  Patients also commonly associate symptoms with specific foods (for example, milk, fat, vegetables).  Whether or not the associations are real, these patients will restrict their diets accordingly.  Milk is the most common food that is eliminated, often unnecessarily, and this can lead to inadequate intake of calcium and osteoporosis.  The interference with daily activities also can lead to problems with interpersonal relationships, especially with spouses.  Most patients with functional disease live with their symptoms and infrequently visit physicians for diagnosis and treatment.

The nerves that control the organs include not only the nerves that lie within the muscles of the organs but also the nerves of the spinal cord and brain.

Some gastrointestinal diseases can be seen and diagnosed with the naked eye, such as ulcers of the stomach.  Thus, ulcers can be seen at surgery, on x-rays, and by endoscopy.  Other diseases cannot be seen with the naked eye but can be seen and diagnosed under the microscope.  For example, gastritis (inflammation of the stomach) is diagnosed by microscopic examination of biopsies of the stomach.  In contrast, gastrointestinal functional diseases cannot be seen with the naked eye or with the microscope.  In some instances, the abnormal function can be demonstrated by tests (for example, gastric emptying studies or antro-duodenal motility studies).  However, the tests often are complex, are not widely available, and do not reliably detect the functional abnormalities.  Accordingly, and by default, functional gastrointestinal diseases are those that involve abnormal function of gastrointestinal organs in which the abnormalities cannot be seen in the organs with either the naked eye or the microscope.

Occasionally, diseases that are called functional are ultimately found to be associated with abnormalities that can be seen.  Then, the disease moves out of the functional category.  An example of this would be Helicobacter pylori (H. pylori) infection of the stomach.  Some patients with mild upper gastrointestinal symptoms who were thought to have abnormal function of the stomach or intestines have been found to have stomachs infected with H. pylori.  This infection is diagnosed under the microscope by identifying the bacterium.  When patients are treated with antibiotics, the H. pylori and symptoms disappear.  Thus, recognition of infections with Helicobacter pylori has removed some patients' systems from the functional disease category.The distinction between functional disease and non-functional disease is blurry.  Thus, even functional diseases probably have associated biochemical or molecular abnormalities that ultimately can be measured.  For example, functional diseases of the stomach and intestines may be shown ultimately to be associated with reduced or increased levels of normal chemicals within the gastrointestinal organs, the spinal cord, or the brain.  Should a disease that is demonstrated to be due to a reduced or increased chemical still be considered a functional disease?  I think not.  In this theoretical situation, we cannot see the abnormality with the naked eye or the microscope, but we can measure it.  If we can measure an associated or causative abnormality, the disease should not be considered functional.

Despite the shortcomings of the term, functional, the concept of a functional abnormality is useful for approaching many of the symptoms originating from the muscular organs of the gastrointestinal tract.  To repeat, this concept applies to those symptoms for which there are no associated abnormalities that can be seen with the naked eye or the microscope.

While dyspepsia is a major functional disease(s), it is important to mention several other functional diseases.  A second major functional disease is the irritable bowel syndrome, or IBS.  The symptoms of IBS are thought to originate primarily from the small intestine and/or colon.  The symptoms of IBS include abdominal pain that is accompanied by alterations in bowel movements (defecation), primarily constipation or diarrhea.  In fact, dyspepsia and IBS may be overlapping diseases since up to half of patients with IBS also have symptoms of dyspepsia.  A third distinct functional disorder is non-cardiac chest pain.  This pain may mimic heart pain (angina), but it is unassociated with heart disease.  In fact, non-cardiac chest pain is thought to result from a functional abnormality of the esophagus.

The organ of involvement categorizes functional disorders of the gastrointestinal tract often.  Thus, there are functional disorders of the esophagus, stomach, small intestine, colon, and gallbladder.  The amount of research that has been done with functional disorders is greatest in the esophagus and stomach (for example, non-cardiac chest pain, dyspepsia), perhaps because these organs are easiest to reach and study.  Research into functional disorders affecting the small intestine and colon (IBS) is more difficult to conduct and there is less agreement among the research studies.  This probably is a reflection of the complexity of the activities of the small intestine and colon and the difficulty in studying these activities.  Functional diseases of the gallbladder (referred to as biliary dyskinesia), as those of the small intestine and colon are more difficult to study, and at present they are less well defined.  Each of the functional diseases is associated with its own set of characteristic symptoms.

Symptoms of Dyspepsia

We usually think of symptoms of dyspepsia as originating from the upper gastrointestinal tract, primarily the stomach and first part of the small intestine.  These symptoms include:

  •  upper abdominal pain (above the navel),
  •  belching,
  •  nausea (with or without vomiting),
  •  abdominal bloating (the sensation of abdominal fullness without objective distention),
  •  early satiety (the sensation of fullness after a very small amount of food), and,
  • possibly, abdominal distention (swelling as opposed to bloating).

The symptoms most often are provoked by eating, which is a time when many different gastrointestinal functions are called upon to work in concert.  This tendency to occur after meals is what gave rise to the notion that dyspepsia may be caused by an abnormality in the digestion of food.
It is appropriate to discuss belching in detail since it is a commonly misunderstood symptom associated with dyspepsia.  The ability to belch is almost universal.  Belching, also known as burping is the act of expelling gas from the stomach out through the mouth.  The usual cause of belching is a distended (inflated) stomach that is caused by swallowed air or gas.  The distention of the stomach causes abdominal discomfort, and the belching expels the air and relieves the discomfort.  The common reasons for swallowing large amounts of air (aerophagia) or gas are gulping food or drinking too rapidly, anxiety, and carbonated beverages.  People often are unaware that they are swallowing air.  Moreover, if there is not excess air in the stomach, the act of belching actually may cause more air to be swallowed.  "Burping" infants during bottle or breastfeeding is important in order to expel air in the stomach that has been swallowed with the formula or milk.

Excessive air in the stomach is not the only cause of belching.  For some people, belching becomes a habit and does not reflect the amount of air in their stomachs.  For others, belching is a response to any type of abdominal discomfort and not just to discomfort due to increased gas.  Everyone knows that when you have mild abdominal discomfort, belching often relieves the problem.  This is because excessive air in the stomach is often the cause of mild abdominal discomfort.  As a result, people belch whenever mild abdominal discomfort is felt-whatever the cause.

If the problem causing the discomfort is not excessive air in the stomach, then belching does not provide relief.  As mentioned previously, it even may make the situation worse by increasing air in the stomach.  When belching does not ease the discomfort, the belching should be taken as a sign that something may be wrong within the abdomen and that the cause of the discomfort should be sought.  Belching by itself, however, does not help the physician determine what may be wrong because belching can occur in virtually any abdominal disease or condition that causes discomfort.

What is the course of dyspepsia (indigestion)?

Dyspepsia is a chronic disease that usually lasts years, if not a lifetime.  It does, however, display  periodicity, which means that the symptoms may be more frequent or severe for days, weeks, or months and then less frequent or severe for days, weeks, or months.  The reasons for these fluctuations are unknown.  Because of the fluctuations, it is important to judge the effects of treatment over many weeks or months to be certain that any improvement is due to treatment and not simply to a natural fluctuation in the frequency or severity of the disease.

What causes dyspepsia (indigestion)?

It is not surprising that many gastrointestinal diseases have been associated with dyspepsia.  However, many non-gastrointestinal diseases also have been associated with dyspepsia.  Examples of the latter include diabetes, thyroid disease, hyperparathyroidism (overactive parathyroid glands), and severe kidney disease.  It is not clear, however, how these non-gastrointestinal diseases might cause dyspepsia.  A second important cause of dyspepsia is drugs.  It turns out that many drugs are frequently associated with dyspepsia, for example, nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen), antibiotics, and estrogens).  In fact, most drugs are reported to cause dyspepsia in at least some patients.

As discussed previously, most dyspepsia (not due to non-gastrointestinal diseases or drugs) is believed to be due to abnormal function (dysfunction) of the muscles of the organs of the gastrointestinal tract or the nerves controlling the organs.  The nervous control of the gastrointestinal tract, however, is complex.  A system of nerves runs the entire length of the gastrointestinal tract from the esophagus to the anus in the muscular walls of the organs.  These nerves communicate with other nerves that travel to and from the spinal cord.  Nerves within the spinal cord, in turn, travel to and from the brain.  (The gastrointestinal tract is exceeded in the numbers of nerves it contains only by the spinal cord and brain.)  Thus, abnormal function of the nervous system in dyspepsia might occur in a gastrointestinal muscular organ, the spinal cord, or the brain.

The nervous system controlling the gastrointestinal organs, as with most other organs, contains both sensory and motor nerves.  The sensory nerves continuously sense what is happening (activity) within the organ and relay this information to nerves in the organ's wall.  From there, information can be relayed to the spinal cord and brain.  The information is received and processed in the organ's wall, the spinal cord, or the brain.  Then, based on this sensory input and the way the input is processed, commands (responses) are sent to the organ over the motor nerves.  Two of the most common motor responses in the intestine are contraction or relaxation of the muscle of the organ and secretion of fluid and/or mucus into the organ.

As already mentioned, abnormal function of the nerves of the gastrointestinal organs, at least theoretically, might occur in the organ, spinal cord, or brain.  Moreover, the abnormalities might occur in the sensory nerves, the motor nerves, or at processing centers in the intestine, spinal cord, or brain.

Some researchers argue that the cause of functional diseases is abnormalities in the function of sensory nerves.  For example, normal activities, such as stretching of the small intestine by food, may give rise to sensory signals that are sent to the spinal cord and brain, where they are perceived as painful.  Other researchers argue that the cause of functional diseases is abnormalities in the function of motor nerves.  For example, abnormal commands through the motor nerves might produce painful spasm (contraction) of the muscles.  Still others argue that abnormally functioning processing centers are responsible for functional diseases because they misinterpret normal sensations or send abnormal commands to the organ.  In fact, some functional diseases may be due to sensory dysfunction, motor dysfunction, or both sensory and motor dysfunction.  Others may be due to abnormalities within the processing centers.

An important concept that is relevant to these several potential mechanisms (causes) of functional diseases is the concept of "visceral hypersensitivity".  This concept states that diseases affecting the gastrointestinal organs (viscera) "sensitize" (alter the responsiveness of) the sensory nerves or the processing centers to sensations coming from the organ.  According to this theory, a disease such as colitis (inflammation of the colon) can cause permanent changes in the sensitivity of the nerves or processing centers of the colon.  Because of this prior inflammation, normal stimuli are perceived (felt) as abnormal (for example, as being painful).  Thus, a normal colonic contraction may be painful.  It is not clear what prior diseases might lead to hypersensitivity in people, although infectious diseases (bacterial or viral) of the gastrointestinal tract are mentioned most often.  Visceral hypersensitivity has been demonstrated clearly in animals and people.  Its role in the common functional diseases, however, is unclear.

Another potential cause of dyspepsia is bacterial overgrowth of the small intestine (small intestinal bacterial overgrowth), although the frequency with which this condition causes dyspepsia has not been determined, and there is little research in the area.  The relationship between overgrowth and dyspepsia needs to be pursued, however, since many of the symptoms of dyspepsia are also symptoms of bacterial overgrowth.  Overgrowth can be diagnosed by hydrogen breath testing and is treated primarily with antibiotics.

Other diseases and conditions can aggravate functional diseases, including dyspepsia.  Anxiety and/or depression are probably the most commonly recognized exacerbating factors for patients with functional diseases.  Another aggravating factor is the menstrual cycle.  During their periods, women often note that their functional symptoms are worse.  This corresponds to the time during which the female hormones, estrogen and progesterone, are at their highest levels.  Furthermore, it has been observed those treating women who have dyspepsia with leuprolide (Lupron), an injectable drug that shuts off the body's production of estrogen and progesterone, is effective at reducing symptoms of dyspepsia in premenopausal women.  These observations support a role for hormones in the intensification of functional symptoms.

As always, a detailed history from the patient and a physical examination frequently will suggest the cause of dyspepsia.  Routine screening blood tests often are performed looking for clues to unsuspected diseases.  Examinations of stool also are a part of the evaluation since they may reveal infection, signs of inflammation, or blood and direct further diagnostic testing.  Sensitive stool testing (antigen/antibody) for Giardia lamblia would be reasonable because this parasitic infection is common and can be acute or chronic.  Some physicians do blood testing for celiac disease (sprue), but the value of doing this is unclear.  (Moreover, if an EGD is planned, biopsies of the duodenum usually will make the diagnosis of celiac disease.)  If bacterial overgrowth of the small intestine is being considered, breath hydrogen testing can be considered.

There are many tests to exclude non-functional gastrointestinal diseases.  The primary issue, however, is to decide which tests are reasonable to perform.  Since each case is individual, different tests may be reasonable for different patients.  Nevertheless, certain basic tests are often performed to exclude non-functional gastrointestinal disease.  These tests identify anatomic (structural) and histological (microscopic) diseases of the esophagus, stomach, and intestines.

Both x-rays and endoscopies can identify anatomic diseases.  Only endoscopies, however, can diagnose histological diseases because biopsies (samples of tissue) can be taken during the procedure.  The x-ray tests include:

1. The esophagram  and video-fluoroscopic swallowing study for examining the esophagus
2. The upper gastrointestinal series for examining the stomach and duodenum
3. The small bowel series for examining the small intestine
4. The barium enema for examining the colon and terminal ileum.
5. The computerized tomography (CT) scan for examining the small intestine
6. The endoscopic tests include:
7. Upper gastrointestinal endoscopy (esophago-gastro-duodenoscopy or EGD) to examine the esophagus, stomach and duodenum
8. Colonoscopy to examine the colon and terminal ileum
9. Endoscopy also is available to examine the small intestine, but this type of endoscopy is complex, not widely available, and of unproven value in dyspepsia.

For examination of the small intestine, there is also a capsule containing a tiny camera and transmitter that can be swallowed (capsule endoscopy).  As the capsule travels through the intestines, it transmits pictures of the inside of the intestines to an external recorder for later review.  The capsule is not widely available and its value, particularly in dyspepsia, has not yet been proven.

X-rays are easier to perform and less costly than endoscopies.  The skills necessary to perform gastrointestinal x-rays, however, are becoming rare among radiologists because they are doing them less often.  Therefore, the quality of the x-rays often is not as high as it used to be, and, as a result, CT scans of the small intestine are replacing small intestinal x-rays.  As noted previously, endoscopies have an advantage over x-rays since at the time of endoscopies, biopsies can be taken to diagnose or exclude histological diseases, something that x-rays cannot do.

Exclusion of acid-related gastrointestinal diseases

Because they are so common, the most important non-functional gastrointestinal diseases to exclude are acid-related diseases that cause inflammation and ulceration of the esophagus, stomach, and duodenum.  Infection of the stomach with Helicobacter pylori, an infection that is closely associated with some acid-related diseases, is included in this group.  It is not clear, however, how often Helicobacter pylori causes dyspepsia.  Moreover, the only way of excluding this bacterium as a cause of dyspepsia in a particular patient is by eliminating the infection (if it is present) with appropriate antibiotics.  If dyspepsia is substantially improved by eradication, it is likely that the bacterium was responsible.  Helicobacter pylori infection can also be diagnosed (or excluded) by blood tests, biopsy of the stomach, urea, or a stool test.

Endoscopy is a good way of diagnosing or excluding acid-related inflammation.  If no signs of inflammation are present, acid-related diseases are unlikely.  Nevertheless, some patients without signs of inflammation respond to potent and prolonged suppression of acid, suggesting that acid is causing their dyspepsia.  Therefore, many physicians will use potent suppression of acid in dyspepsia as a means to both treat and diagnose.  Thus, if dyspepsia improves substantially (more than 50% to 75%) with suppression of acid, they consider it likely that acid is responsible for the dyspepsia.  For this purpose, it is important to use potent acid suppression with proton pump inhibitors (PPIs), such as:

  • omeprazole (Prilosec, Zegerid),
  • lansoprazole (Prevacid),
  • rabeprazole (Aciphex),
  • pantoprazole (Protonix) or
  • esomeprazole (Nexium).

Treatment often is given at higher than recommended doses for 12 weeks or more before a decision is made about the effect of treatment on the symptoms.  (A short course for just a few days or weeks is not enough.)  If the symptoms of dyspepsia do not improve, it even may be reasonable to check the amount of acid produced by the stomach (and the reflux of acid into the esophagus) by 24-hour ph monitoring to be certain that the acid-suppressing drugs are effectively suppressing acid.  (Up to 10% of patients are resistant to the effects of even the PPIs.)

Exclusion of non-gastrointestinal disease

Patients with dyspepsia often undergo abdominal ultrasonography (US), computerized tomography (CT or CAT scans), or magnetic resonance imaging (MRI).  These tests are used primarily to diagnose non-intestinal diseases.  (Although the tests also are capable of diagnosing intestinal diseases, their value for this purpose is limited.  X-ray and endoscopy are better.)  It is important to realize that CT, MRI, and US are powerful tests and may uncover abnormalities that are unrelated to dyspepsia.  The most common example of this is the finding of gallstones that, in fact, are causing no symptoms.  (Up to 50% of gallstones cause no symptoms.)  This can cause a problem if the gallstones are assumed to be causing the dyspepsia.  Surgical removal of the gallbladder with its gallstones (cholecystectomy) is unlikely to relieve the dyspepsia.  (Cholecystectomy would be expected to relieve only the characteristic symptoms that gallstones can cause.)  Additional tests to exclude non-gastrointestinal diseases may be appropriate in certain specific situations, although certainly not in most patients.

Exclusion of psychiatric disease

The possibility of psychiatric (psychological or psychosomatic) illness often arises in patients with dyspepsia because the symptoms are subjective and no objective abnormalities can be identified.  Psychiatric illness may complicate dyspepsia, but it is unclear if psychiatric illness causes dyspepsia.  If there is a possibility of psychiatric illness, a psychiatric evaluation is appropriate.

Treatment

The initial approach to dyspepsia, whether it is treatment or testing, depends on the patient's age, symptoms and the duration of the symptoms.  If the patient is younger than 50 years of age and serious disease, particularly cancer, is not likely, testing is less important.  If the symptoms are typical for dyspepsia and have been present for many years without change, then there is less need for testing, or at least extensive testing, to exclude other gastrointestinal and non-gastrointestinal diseases.

On the other hand, if the symptoms are of recent onset (weeks or months), progressively worsening, severe, or associated with "warning" signs, then early, more extensive testing is appropriate.  Warning signs include loss of weight, nighttime awakening, blood in the stool or the material that is vomited (vomitus), and signs of inflammation, such as fever or abdominal tenderness.  Testing also is appropriate if, in addition to symptoms of dyspepsia, there are other prominent symptoms that are not commonly associated with dyspepsia.
The treatment of dyspepsia is a difficult and unsatisfying topic because so few drugs have been shown to be effective.  Moreover, the drugs that have been shown to be useful have not been substantially effective.  This difficult situation exists for many reasons, as follows:

Life-threatening illnesses (for example, cancer, heart disease, and high blood pressure) are the illnesses that capture the public's interest and, more importantly, research funding.  Dyspepsia is not a life-threatening illness and has received little research funding.  Because of the lack of research, an understanding of the physiologic processes (mechanisms) that are responsible for dyspepsia has been slow to develop.  Effective drugs cannot be developed until there is an understanding of these mechanisms.

Research in dyspepsia is difficult.  Subjective symptoms (such as pain) rather than objective signs (for example, the presence of an ulcer) define dyspepsia.  Subjective symptoms are more unreliable than objective signs in identifying homogenous groups of patients.  As a result, groups of patients with dyspepsia who are undergoing treatment are likely to contain some patients who do not have dyspepsia, which may dilute (negatively affect) the results of the treatment.  Moreover, the results of treatment must be evaluated based on subjective responses (such as improvement of pain).  In addition to being more unreliable, subjective responses are more difficult to measure than objective responses (for example, healing of an ulcer).

Physiologic

The lack of understanding of the physiologic processes (mechanisms) that cause dyspepsia has meant that treatment usually cannot be directed at the mechanisms.  Instead, treatment usually is directed at the symptoms.

Diet

Dietary factors have not been well studied in the treatment of dyspepsia.  Nevertheless, patients often associate their symptoms with specific foods (such as salads and fats).  Although specific foods might worsen the symptoms of dyspepsia, it is clear that they are not the cause of dyspepsia.  The common placebo response in functional disorders such as dyspepsia also may explain the improvement of symptoms in some people with the elimination of specific foods.

Psychotropic drugs

Patients with functional disorders, including dyspepsia, are frequently found to be suffering from depression and/or anxiety.  It is unclear, however, if the depression and anxiety are the cause or result of the functional disorders or are unrelated to these disorders.  (Depression and anxiety are common and, therefore, their occurrence together with functional disorders may be coincidental.)  Several clinical trials have shown that antidepressants are effective in IBS in relieving abdominal pain.  Antidepressants also have been shown to be effective in unexplained (non-cardiac) chest pain, a condition thought to represent a dysfunction of the esophagus.  Antidepressants have not been studied adequately in other types of functional disorders, including dyspepsia.  It probably is reasonable to treat patients with dyspepsia with psychotropic drugs if they have moderate or severe depression or anxiety.

The antidepressants work in dyspepsia and in functional esophageal pain at relatively low doses that have little or no effect on depression.  It is believed, therefore, that these drugs work not by combating depression, but in different ways (through different mechanisms).  For example, these drugs have been shown to adjust (modulate) the activity of the nerves and to have analgesic (pain-relieving) effects as well.

Commonly used psychotropic drugs include the tricyclic antidepressants, desipramine (Norpramine) and trimipramine (Surmontil).  Although studies are encouraging, it is not yet clear whether the newer class of antidepressants, the serotonin-reuptake inhibitors such as fluoxetine(Prozac), sertraline (Zoloft), and paroxetine (Paxil), are effective in functional disorders, including dyspepsia.

Psychological treatments

Psychological treatments include cognitive-behavioral therapy, hypnosis, psychodynamic or interpersonal psychotherapy, and relaxation/stress management.  Few studies of psychological treatments have been conducted in dyspepsia, although more studies have been done in IBS.  Thus, there is little scientific evidence that they are effective in dyspepsia, although there is some evidence that they are effective in IBS.

Promotility drugs

One of the leading theories for the cause of dyspepsia is abnormalities in the very gastrointestinal muscles function.  The function of muscles may be abnormally increased, abnormally decreased, or it may by uncoordinated.  There are medications, called smooth muscle relaxants that can reduce the activity of the muscles and other drugs that can increase the activity of the muscles, called the promotility drugs.

<>pMany of the symptoms of dyspepsia can be explained based on reduced activity of the gastrointestinal muscles that results in slowed transport (transit) of food through the stomach and intestine.  (It is clear, as discussed previously, that there are other causes of these symptoms in addition to slowed transit.)  Such symptoms include nausea, vomiting, and abdominal bloating.  When transit is severely affected, abdominal distention, (swelling) also may occur and can result in abdominal pain.  Theoretically, drugs that speed up the transit of food should, in at least some patients, relieve symptoms of dyspepsia that are due to slow transit.

The number of promotility drugs that are available for use clinically is limited.  Studies of their effectiveness in dyspepsia are even more limited.  The most studied drug is cisapride (Propulsid), a promotility drug that was withdrawn from the market because of serious cardiac side effects.

Another promotility drug that is available is erythromycin, an antibiotic that stimulates gastrointestinal smooth muscle as one of its side effects.  Erythromycin is used to stimulate smooth muscles of the gastrointestinal tract at doses that are lower than those used for treating infections are.  There are no studies of erythromycin in dyspepsia, but erythromycin is effective in gastroparesis and probably also in chronic intestinal pseudo-obstruction.

Metoclopramide (Reglan) is another promotility drug that is available.  It has not been studied, however, in dyspepsia.  Moreover, it is associated with some troubling side effects.  Therefore, it may not be a good drug to undergo further testing in dyspepsia.
Domperidone (Motilium) is a promotility drug that is available in the U.S., but requires a special permit from the US Food and Drug administration.  As a result, it is not very commonly prescribed.  It is an effective drug with minimal side effects.

Smooth muscle relaxants

The most widely studied drugs for the treatment of abdominal pain in functional disorders are a group of drugs called smooth-muscle relaxants.
The gastrointestinal tract is primarily composed of a type of muscle called smooth muscle.  (By contrast, skeletal muscles such as the biceps are composed of a type of muscle called striated muscle.)  Smooth muscle relaxant drugs reduce the strength of contraction of the smooth muscles but do not affect the contraction of other types of muscles.  They are used in functional disorders, particularly IBS, with the assumption (not proven) that strong or prolonged contractions of smooth muscles in the intestine-spasms-are the cause of the pain in functional disorders.  There are even smooth muscle relaxants that are placed under the tongue so that they may be absorbed rapidly.

The future of dyspepsia will depend on our increasing knowledge of the processes (mechanisms) that cause dyspepsia.  Acquiring this knowledge, in turn, depends on research funding.  Because of the difficulties in conducting research in dyspepsia, this knowledge will not come quickly.  Until we have an understanding of the mechanisms of dyspepsia, newer treatments will be based on our developing a better understanding of the normal control of gastrointestinal function, which is proceeding more rapidly.  Specifically, there is intense interest in intestinal neurotransmitters, which are chemicals that the nerves of the intestine use to communicate with each other.  The interactions of these neurotransmitters are responsible for adjusting (modulating) the functions of the intestines, such as contraction of muscles and secretion of fluid and mucus.

Cannabinoids Relieve Dyspepsia Symptoms

Medical marijuana can be used to eliminate all the symptoms of dyspepsia with little to no side effects.  It seems to me to be the logical answer.

1. relaxes the smooth muscles
2. through neurotransmitters it modulates the functions of the intestines
3. stops pain
4. stops nausea

You probably will not have to take most of the pharmaceuticals you were prescribed.  That is good because so many drugs have nasty side effects that can be worse than the dyspepsia itself.
Recommendation:  Sativa x Indica hybrid.  Tinctures (under the tongue), suppositories, teas, vaporizer, edibles (maybe), butter.  Use whole plant extracts.

Cannabinoid Studies

Studies indicate that cannabinoids in marijuana bind with cannabinoid receptors in the digestive tract, especially the small and large intestine, causing muscle relaxation, reduction of inflammation, analgesia, increased nerve-muscle coordination, anti-emesis, and relief of spasms such as those that cause nausea. 

Cannabis is also an adaptogenic immune system modulator that can increase or decrease immune systems function in ways that usually contribute to healthier outcomes. 

Cannabis is unique among medicines because it has a comprehensive range of actions that can alleviate several symptoms by altering how the body and brain communicate, and how the self perceives its internal organs and systems.
Medical marijuana to treat digestive system problems is time-tested, and is usually a safer intervention than the use of pharmaceutical drugs or surgery.
"For patients who suffer simultaneously from severe pain, nausea, and appetite loss, cannabinoid drugs might offer broad-spectrum relief not found in any other single medication."
Involvement of cannabinoid receptors in gut motility and visceral perception.
Cannabis helps combat cramping that accompanies many GI disorders because cannabinoids relax contractions of the smooth muscle of the intestines.  Research shows that the body’s own cannabinoids, known as anandamides, affect neurological systems that control the gastrointestinal system.  External and internal cannabinoids strongly control gastrointestinal motility and inflammation.  They also have the ability to decrease gastrointestinal fluid secretion and inflammation.  This means that cannabis can be useful to stop ulcers and other syndromes. 

The chronic pain and spasms that accompany many gastrointestinal disorders are a life hindrance to those who suffer from IBS and other diseases.  Medical cannabis is a very effective pain reliever.  It blocks spinal, peripheral and gastrointestinal mechanisms that promote pain in IBS and related disorders.  It also can be used against gastroesophageal reflux disease (acid reflux).  When acid reflux occurs, gastric acids attack the esophagus.  The pharmaceutical medicines that doctors prescribe for this condition are in some ways as bad as the condition itself.  They prescribe drugs like atropine, for example, which have severe side effects.

Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation From a historical perspective to the present day, all the evidence suggests that activation of cannabinoid receptors (CBRs) is beneficial for gut discomfort and pain, which are symptoms related to dysmotility and visceral perception.  CBRs comprise G-protein coupled receptors that are Predominantly in enteric and central neurons (CB1R) and immune cells (CB2R).  In the last decade, evidence obtained from the use of selective agonists and inverse agonists/antagonists indicates that manipulation of CB1R can alter (1) sensory processing from the gut, (2) brain integration of brain-gut axis, (3) extrinsic control of the gut and (4) intrinsic control by the enteric nervous system.  The extent to which activation of CB1R is most critical at these different levels is related to the region of the GI tract.  The upper GI tract is strongly influenced by CB1R activation on central vagal pathways, whereas intestinal peristalsis can be modified by CB1R activation in the absence of extrinsic input. Actions at multiple levels make the CB1R a target for the treatment of functional bowel disorders, such as IBS.  Since low-grade inflammation may act as a trigger for occurrence of IBS, CB2R modulation could be beneficial, but there is little supporting evidence for this yet.  The challenge is to accomplish CBR activation while minimizing adverse effects and abuse liabilities.  Potential therapeutic strategies involve increasing signaling by endocannabinoids (EC).  The pathways involved in the biosynthesis, uptake and degradation of ECprovide opportunities for modulation of CB1R and some recent evidence with inhibitors of ECuptake and metabolism suggest that these could be exploited for therapeutic gain.

In conclusion, tremendous progress has been made in the last decade to demonstrate the role and site of action of CBR agonists in many aspects of GI function.  The beneficial effects of CB1R activation in animal models include reduction of transient lower esophageal sphincter relaxations, increased compliance of the proximal stomach, reduced acid secretion, reduction of GI transit, reduced intestinal fluid secretion in response to secretogogues and reduced large intestinal propulsive activity are all aspects that could be beneficial in functional bowel disorders such as IBS.  However, administration of CB1R agonists to patients would be associated with CBS adverse effects due to the psychotropic actions.  It is not clear to what extent increasing the release, or reducing the uptake of ECs would be beneficial for treatment of GI disorders.  However, there is emerging evidence for tonic EC release in both physiological and pathophysiological systems suggests that these are important molecules in control of the GI tract.  Newer approaches to their modulation by inhibition of FAAH or the uptake mechanisms hold promise for future therapeutic avenues.  However, whether these approaches can be successful depends on minimizing CNS adverse effects, and it is not known whether such manipulation would also evoke psychotropic central effects associated with CB1R activation.  The ideal approach would be to increase the levels of ECs within the dorsal vagal complex (a region that is less protected by the blood–brain- barrier), the vagal pathways, and the dorsal root ganglion and within the enteric nervous system, without affecting higher brain function.  This would hold the greatest promise for minimizing risks while treating or ameliorating the symptoms of complicated disorders with unclear etiology such as IBS.
Cannabinoid agonist inhibits gastrointestinal motility.  The endocannabinoid, anandamide, is inactivated by fatty acid amide hydrolase (FAAH).  A single nucleotide polymorphism in the human FAAH gene (C385A) reduces FAAH expression.  Our aim was to evaluate associations between FAAH genotype variation and symptom phenotype, gastric emptying and volume, colonic transit, and rectal sensation in patients with functional gastrointestinal disorders (FGID).  482 FGID patients [Rome II positive, 159 constipation disorders, 184 diarrhea disorders (D-IBS), 86 mixed bowel function (M-IBS), 20 chronic abdominal pain (CAP), 33 functional dyspepsia], and 252 healthy volunteers (HV) underwent questionnaires and studies of phenotype and genotype from 2000 to 2007: 250 gastric emptying, 210 fasting and postprandial gastric volume, 152 colonic transit, and 123 rectal sensation.  All had FAAH genotype [CC vs. polymorphic (CA/AA)] determined by TaqMan.  FAAH genotype distribution of FGID patients and HV did not deviate from Hardy-Weinberg equilibrium.  There was a significant association of FAAH genotype with FGID phenotype (overall χ2, P = 0.011) and with specific individual phenotypes (P = 0.048).  Thus FAAH CA/AA increases the odds (relative to HV) for D-IBS (P = 0.008), M-IBS (P = 0.012), and, possibly, CAP (P = 0.055).  There was a significant association of FAAH CA/AA genotype with accelerated colonic transit in D-IBS (P = 0.037).  There was no association of FAAHgenotype with rectal sensation thresholds or ratings.  The association of genetic variation in metabolism of endocannabinoids with symptom phenotype in D-IBS and M-IBS and with faster colonic transit in D-IBS supports the hypothesis that cannabinoid mechanisms may play a role in the control of colonic motility in humans and deserve further study.

CANNABINOID (CB) receptors are located on cholinergic neurons in the brain stem, stomach, and colon.
Cannabinoid CB1 Receptors Are Expressed by Parietal Cells of the Human Gastric Mucosa

Abstract

Experimental data suggest that the endogenous cannabinoid system is involved in gastric function in different animal species.  In most of them, CB1 receptors have been localized on vagal terminals innervating the external wall of the stomach.  We aimed at studying the putative presence and distribution of these receptors in the human gastric mucosa.  To this end, we first performed Western blotting, RT-PCR, in situ hybridization, and immunohistochemical analysis of CB1 protein distribution in biopsy samples of healthy individuals.  To determine the precise cell populations expressing CB1 receptors, we performed double immunofluorescence plus confocal microscopy analysis of the same samples.  Our results show that CB1 receptors are present in the gastric epithelium of the mucosa.  Specifically, they are expressed by a subpopulation of mucosal cells, the acid-secreting parietal cells, as shown by double immunohistochemical staining and by their differential abundance in sub regions of the gastric mucosa.  These results reinforce the notion of a prominent role for the endocannabinoid system in the gastric function in humans and postulate the use of cannabinoid CB1 receptors in parietal cells as new therapeutic targets for the regulation of gastric acid production.

CB1-mediated effects are being studied in a number of paradigms, mainly at the vascular and central nervous system (CNS) levels.  However, growing evidence supports the idea that the endocannabinoid system (ECS) (constituted by receptors, endogenous ligands, and enzymes responsible for their synthesis and degradation) plays a prominent role in other physiological systems.  Among them, gastrointestinal function is one of the most relevant, because cannabinoids have been long known to modify several digestive functions, such as gastric emptying, appetite, and intestinal motility (Pertwee 2001; Coutts and Izzo 2004).  These actions are exerted through receptors located in the CNS.

Cannabinoids have been known for their analgesic, anxiolytic, anti emetic and anti spastic properties for many centuries.  We believe that research that will bring the medicinal use of cannabis into the light of the public eye of believers and unbelievers unmasking the power of this 100% naturally occurring herbal medicine.  The endogenous cannabinoid system has been identified in the past two decades, and this has brought much interest in western medicine.  Nearly 100% of Patients report that cannabis is safe and effective.  The endocannabinoid system may serve important functions in the central and peripheral regulation of pain.  Alteration in the perception of and reaction to pain and muscle spasticity or spasms is a unique property of cannabis therapy.  Cannabinoids have analgesic, immunomodulatory and anti-inflammatory properties.

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