GASTROESOPHGEAL REFLUX DISORDER-GERD
What is GERD?
Gastro esophageal reflux disease (GERD) is a more serious form of gastro esophageal reflux (GER), which is common. GER occurs when the lower esophageal sphincter (LES) opens spontaneously, for varying periods, or does not close properly and stomach contents rise up into the esophagus. GER is also called acid reflux or acid regurgitation, because digestive juices—called acids—rise up with the food. The esophagus is the tube that carries food from the mouth to the stomach. The LES is a ring of muscle at the bottom of the esophagus that acts like a valve between the esophagus and stomach.
When acid reflux occurs, food or fluid can be tasted in the back of the mouth. When refluxed stomach acid touches the lining of the esophagus it may cause a burning sensation in the chest or throat called heartburn or acid indigestion. Occasional GER is common and does not necessarily mean one has GERD. Persistent reflux that occurs more than twice a week is considered GERD, and it can eventually lead to more health that is serious problems. People of all ages can have GERD.
Gastro esophageal reflux disease (GERD), gastro-esophageal reflux disease (GORD), gastric reflux disease, or acid reflux disease is chronic symptoms or mucosal damage caused by stomach acid coming up from the stomach into the esophagus. A typical symptom is heartburn.
GERD is usually caused by changes in the barrier between the stomach and the esophagus, including abnormal relaxation of the lower esophageal sphincter, which normally holds the top of the stomach closed; impaired expulsion of gastric reflux from the esophagus, or a hiatal hernia. These changes may be permanent or temporary.
Signs and symptoms
The most-common symptoms of GERD are:
Trouble swallowing (dysphagia)
Less-common symptoms include:
Pain with swallowing (odynophagia)
Excessive salivation (also known as water brash) is common during heartburn, as saliva is generally slightly alkaline and is the body's natural response to heartburn, acting similarly to an antacid)
GERD sometimes causes injury of the esophagus. These injuries may include:
1. Reflux esophagitis – necrosis of esophageal epithelium causing ulcers near the junction of the stomach and esophagus.
2. Esophageal strictures – the persistent narrowing of the esophagus caused by reflux-induced inflammation.
3. Barrett's esophagus – intestinal metaplasia (changes of the epithelial cells from squamous to intestinal columnar epithelium) of the distal esophagus.
4. Esophageal adenocarcinoma – a rare form of cancer.
Several other atypical symptoms are associated with GERD, but there is good evidence for causation only when they are accompanied by esophageal injury. These symptoms are:
- Chronic cough
- Laryngitis (hoarseness, throat clearing)
- Erosion of dental enamel
- Dentine hypersensitivity
- Sinusitis and damaged teeth
Some people have proposed that symptoms such as sinusitis, recurrent ear infections, and idiopathic pulmonary fibrosis are due to GERD; however, a causative role has not been established.
Every year GERD affects approximately 4.5 per 1000 persons in the United Kingdom and 5.4 per 1000 persons in the United States. It is possible, given the limitations of the relevant studies, that these figures will be larger than estimated.
In Western populations, the prevalence range for GERD is 10% to 20% of the population. The prevalence rate of GERD in developed nations is also tightly linked with age, with adults aged 60 to 70 being the most commonly affected. The combination of longer life expectancy and aging populations in the developed world will lead to an increase in GERD prevalence in the years to come.
What causes GERD?
The reason some people develop GERD is still unclear. However, research shows that in people with GERD, the LES relaxes while the rest of the esophagus is working. Anatomical abnormalities such as a hiatal hernia may also contribute to GERD. A hiatal hernia occurs when the upper part of the stomach and the LES move above the diaphragm, the muscle wall that separates the stomach from the chest. Normally, the diaphragm helps the LES keep acid from rising up into the esophagus. When a hiatal hernia is present, acid reflux can occur more easily. A hiatal hernia can occur in people of any age and is most often a normal finding in otherwise healthy people over age 50. Most of the time, a hiatal hernia produces no symptoms.
Other factors that may contribute to GERD include
Common foods that can worsen reflux symptoms includecitrus fruits
drinks with caffeine or alcohol
fatty and fried foods
garlic and onions
tomato-based foods, like spaghetti sauce, salsa, chili, and pizza
Three types of treatments exist for GERD. These include lifestyle modifications, medications, and surgery.
Certain foods and lifestyle are considered to promote gastro esophageal reflux, but a 2006 review suggested that evidence for most dietary interventions is anecdotal; only weight loss and elevating the head of the bed were supported by evidence. A subsequent randomized study showed benefit by avoiding eating two hours before bedtime.
The following may exacerbate the symptoms of GERD:
Antacids based on calcium carbonate (but not aluminium hydroxide) were found to actually increase the acidity of the stomach. However, all antacids reduced acidity in the lower esophagus, so the net effect on GERD symptoms may still be positive.
Smoking reduces lower esophageal sphincter competence, thus allowing acid to enter the esophagus.
Sleeping on the left side seems to reduce nighttime reflux episodes in patients.
A meta-analysis suggested that elevating the head of the bed is an effective therapy, although this conclusion was only supported by nonrandomized studies. The head of the bed can be elevated by plastic or wooden bed risers that support bed posts or legs, a therapeutic bed wedge pillow, a wedge or an inflatable mattress lifter that fits in between mattress and box spring or a hospital bed with an elevate feature. The height of the elevation is critical and must be at least 6 to 8 inches (15 to 20 cm) to be at least minimally effective to prevent the backflow of gastric fluids. Some innerspring mattresses do not work well when inclined and may cause back pain; some prefer foam mattresses. Some practitioners use higher degrees of incline than provided by the commonly suggested 6 to 8 inches (15 to 20 cm) and claim greater success.
The current gold standard for diagnosis of GERD is esophageal pH monitoring. It is the most objective test to diagnose the reflux disease and it allows monitoring GERD patients in regards of their response to medical or surgical treatment. One practice for diagnosis of GERD is a short-term treatment with proton pump inhibitors, with improvement in symptoms suggesting a positive diagnosis. According to a systematic review, short-term treatment with proton pump inhibitors may help predict abnormal 24-hr pH monitoring results among patients with symptoms suggestive of GERD.
In general, an EGD is done when the patient neither does not respond well to treatment nor has alarm symptoms including dysphagia, anemia, blood in the stool (detected chemically), wheezing, weight loss, or voice changes. Some physicians advocate either once-in-a-lifetime or 5/10-yearly endoscopy for patients with longstanding GERD, to evaluate the possible presence of dysplasia or Barrett's esophagus, a precursor lesion for esophageal adenocarcinoma.
Esophagogastroduodenoscopy (EGD) (a form of endoscopy) involves insertion of a thin scope through the mouth and throat into the esophagus and stomach (often while the patient is sedated) in order to assess the internal surfaces of the esophagus, stomach, and duodenum.
Biopsies can be performed during gastroscopy and these may show:
Edema and basal hyperplasia (non-specific inflammatory changes)
Lymphocytic inflammation (non-specific)
Neutrophilic inflammation (usually due to reflux or Helicobacter gastritis)
Eosinophilic inflammation (usually due to reflux). The presence of intraepithelial eosinophils may suggest a diagnosis of eosinophilic esophagitis (EE) if eosinophils are present in high enough numbers. Less than 20 eosinophils per high-power microscopic field in the distal esophagus, in the presence of other histologic features of GERD, are more consistent with GERD than EE.
Goblet cell intestinal metaplasia or Barretts esophagus
Elongation of the papillae
Thinning of the squamous cell layer
Dysplasia or pre-cancer
Reflux changes may be non-erosive in nature, leading to the entity "non-erosive reflux disease".
A number of drugs are approved to treat GERD, and are among the most prescribed medication in Western countries.
Proton pump inhibitors (such as omeprazole, esomeprazole, pantoprazole, lansoprazole, and rabeprazole) are the most effective in reducing gastric acid secretion. These drugs stop acid secretion at the source of acid production, i.e., the proton pump.
Gastric H2 receptor blockers (such as ranitidine, famotidine and cimetidine) can reduce gastric secretion of acid. These drugs are technically antihistamines. They relieve complaints in about 50% of all GERD patients. Compared to placebo (which also is associated with symptom improvement), they have a number needed to treat (NNT) of eight
Antacids before meals or symptomatically after symptoms begin can reduce gastric acidity (increase pH).
Alginic acid (Gaviscon) may coat the mucosa as well as increase pH and decrease reflux. A meta-analysis of randomized controlled trials suggests alginic acid may be the most effective of non-prescription treatments with a NNT of four.
Prokinetics strengthen the lower esophageal sphincter (LES) and speed up gastric emptying. Cisapride, a member of this class, was withdrawn from the market for causing long QT syndrome. Reglan (metoclopramide) is a prokinetic with a better side-effect profile.
Sucralfate (Carafate) is also useful as an adjunct in helping to heal and prevent esophageal damage caused by GERD, however it must be taken several times daily and at least two (2) hours apart from meals and medications.
Mosapride citrate is a 5-HT4 receptor agonist used outside the United States largely as a therapy for GERD and dyspepsia.
Baclofen is an agonist of GABAB receptor. In addition to its skeletal muscle relaxant properties, it has also been shown to decrease transient lower esophageal sphincter relaxations at a dose of 10mg given four times daily. Reductions in esophageal relaxation clinically reduce episodes of reflux.
Clinical trials that compare GERD treatments head-to-head provide physicians with critical information. Unfortunately, most pharmaceutical-company sponsored studies are conducted versus placebo and not an active control. However, the DIAMOND has shown rough equivalence of efficacy between a "step-up" approach to therapy (antacids, followed by histamine antagonists, followed by PPIs) and a "step-down" approach (the reverse). The primary endpoint of the study was treatment success after six months, and was achieved for 70% of patients in "step-down" versus 72% of patients in "step-up
The standard surgical treatment is the Nissen fundoplication. In this procedure, the upper part of the stomach is wrapped around the lower esophageal sphincter (LES) to strengthen the sphincter and prevent acid reflux and to repair a hiatal hernia. The procedure is often done laparoscopically. When compared to medical management laparoscopic fundoplication had better results at 1 year. In addition, laparoscopic fundoplication may reduce SF-36 score (quality of life questionnaire) among patients with gastro-esophageal reflux disease as compared to medical management according to a Cochrane systematic review of randomized controlled trials. There were statistically significant improvements in quality of life at 3 months and 1 year after surgery compared to medical therapy, with an SF-36 general health score mean difference of -5.23 in favor of surgery (95%CI = -6.83 to -6.82).
An obsolete treatment is vagotomy ("highly selective vagotomy"), the surgical removal of vagus nerve branches that innervate the stomach lining. This treatment has been largely replaced by medication.
Another treatment is transoral incision less fundoplication (TIF) with the use of a device called Esophyx, which allows doctors to rebuild the valve between the stomach and the esophagus by going through the esophagus
In 2000, the U.S. Food and Drug Administration (FDA) approved two endoscopic devices to treat chronic heartburn. One system, Endocinch, puts stitches in the LES to create little pleats that help strengthen the muscle. However, long-term results were disappointing, and Bard no longer sells the device. Another, the Stretta Procedure, uses electrodes to apply radio frequency energy to the LES. The long-term outcomes of both procedures compared to a Nissen fundoplication are still being determined.
Subsequently the FDA for endoscopic GERD treatment cleared the NDO Surgical Plicator. The Plicator creates a plication, or fold, of tissue near the gastro esophageal junction, and fixates the plication with a suture-based implant. The company ceased operations in mid 2008, and the device is no longer on the market.
Relief is often found by raising the head of the bed, raising the upper body with pillows, or sleeping sitting up. Avoid pillows that raise the head only, as this does little for heartburn and places continuous strain on the neck. Eating a big meal causes excess stomach acid production, and attacks can be minimized by eating small frequent meals instead of large meals, especially for dinner. To minimize attacks, a sufferer may benefit from avoiding foods that may trigger their symptoms. These may include acidic fruit or juice, fatty foods, pretzels, coffee, tea, onions, peppermint, chocolate, or highly spiced foods, especially shortly before bedtime While there are clearly other health-related benefits associated with dietary interventions, a zealous recommendation for dietary restrictions is not evidence-based, and there is stronger support for reducing the symptoms of acid reflux found in behavioral changes such as eating less and elevating the head of the bed while sleeping. Tight clothing around the abdomen can also increase the risk of heartburn because it puts pressure on the stomach, which can cause the food and acids in the stomach to reflux to the lower esophageal sphincter.
Cannabinoids are Effective in Treating Symptoms:
Research suggests that cannabis is effective in treating the symptoms of these GI disorders in part because it interacts with the endogenous cannabinoid receptors in the digestive tract, which can result in calming spasms, assuaging pain, and improving motility. Cannabis has also been shown to have anti-inflammatory properties and recent research shows crucial neuromodulatory roles in controlling the operation of the gastrointestinal system, with synthetic and natural cannabinoids acting powerfully to control gastrointestinal motility and inflammation.
Cannabinoid receptors comprise G-protein coupled receptors that are predominantly in enteric and central neurones (CB1R) and immune cells (CB2R). The digestive tract contains endogenous cannabinoids (anandamide and 2-arachidonylglycerol) and cannabinoid CB1 receptors can be found on myenteric and sub mucosal nerves. Activating cannabinoid receptors has been demonstrated to inhibit gastrointestinal fluid secretion and inflammation in animal models.
In the last decade, evidence obtained from the use of selective agonists and inverse agonists/antagonists indicates that manipulation of CB1R can have significant results. Research has also shown that in the case of intestinal inflammation, the body will increase the number of cannabinoid receptors in the area in an attempt to regulate the inflammation by processing more cannabinoids.
In the past centuries, different preparations of marijuana have been used for the treatment of gastrointestinal (GI) disorders, such as GI pain, gastroenteritis and diarrhea. Delta9-tetrahydrocannabinol (THC; the active component of marijuana), as well as endogenous and synthetic cannabinoids, exert their biological functions on the gastrointestinal tract by activating two types of cannabinoid receptors, cannabinoid type 1 receptor (CB1 receptor) and cannabinoid type 2 receptor (CB2 receptor). While CB1 receptors are located in the enteric nervous system and in sensory terminals of vagal and spinal neurons and regulate neurotransmitter release, CB2 receptors are mostly distributed in the immune system, with a role presently still difficult to establish. Under pathophysiological conditions, the endocannabinoid system conveys protection to the GI tract, eg. from inflammation and abnormally high gastric and enteric secretion. For such protective activities, the endocannabinoid system may represent a new promising therapeutic target against different GI disorders, including frankly inflammatory bowel diseases (Crohn's disease), functional bowel diseases (irritable bowel syndrome), and secretion- and motility-related disorders.
Delta(9)-Tetrahydrocannabinol (the active ingredient of marijuana), as well as endogenous and synthetic cannabinoids, exert many biological functions by activating two types of cannabinoid receptors, CB(1) and CB(2) receptors. CB (1) receptors have been detected on enteric nerves, and pharmacological effects of their activation include gastroprotection, reduction of gastric and intestinal motility and reduction of intestinal secretion. The digestive tract also contains endogenous cannabinoids (i.e., the endocannabinoids anandamide and 2-aracidonylglycerol) and mechanisms for endocannabinoid inactivation (i.e., endocannabinoids uptake and enzymatic degradation). Cannabinoid receptors, endocannabinoids and the proteins involved in endocannabinoids inactivation are collectively referred as the 'endogenous cannabinoid system. A pharmacological modulation of the endogenous cannabinoid system could provide new therapeutics for the treatment of a number of gastrointestinal diseases, including nausea and vomiting, gastric ulcers, irritable bowel syndrome, Crohn's disease, secretory diarrhea, paralytic ileum and gastro esophageal reflux disease. Some cannabinoids are already in use clinically, for example, nabilone and delta (9)-tetrahydrocannabinols are used as antiemetics.
The digestive tract contains endogenous cannabinoids (anandamide and 2-arachidonylglycerol) and cannabinoid CB1 receptors can be found on myenteric and submucosal nerves. Activation of CB1 receptors inhibits gastrointestinal motility, intestinal secretion and gastric acid secretion. The enteric location of CB1 receptors could provide new strategies for the management of gut disorders.
Cannabis has been used to treat gastrointestinal (GI) conditions that range from enteric infections and inflammatory conditions to disorders of motility, emesis and abdominal pain. The mechanistic basis of these treatments emerged after the discovery of Delta (9)-tetrahydrocannabinol as the major constituent of Cannabis. Further progress was made when the receptors for Delta (9)-tetrahydrocannabinol were identified as part of an endocannabinoid system, that consists of specific cannabinoid receptors, endogenous ligands and their biosynthetic and degradative enzymes. Anatomical, physiological and pharmacological studies have shown that the endocannabinoid system is widely distributed throughout the gut, with regional variation and organ-specific actions. It is involved in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation and cell proliferation in the gut. Cellular targets have been defined that include the enteric nervous system, epithelial and immune cells. Molecular targets of the endocannabinoid system include, in addition to the cannabinoid receptors, transient receptor potential vanilloid 1 receptors, peroxisome proliferator-activated receptor alpha-receptors and the orphan G-protein coupled receptors, GPR55 and GPR119. Pharmacological agents that act on these targets have been shown in preclinical models to have therapeutic potential. Here, we discuss cannabinoid receptors and their localization in the gut, the proteins involved in endocannabinoid synthesis, degradation, and the presence of endocannabinoids in the gut in health and disease. We focus on the pharmacological actions of cannabinoids in relation to GI disorders, highlighting recent data on genetic mutations in the endocannabinoid system in GI disease.
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.
Activating cannabinoid receptors has been demonstrated to inhibit gastrointestinal fluid secretion and inflammation in animal models. 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.
Cannabinoids have a demonstrated ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in IBS and related disorders. Animal research also indicates that cannabinoids work well in controlling gastroesophageal reflux disease, a condition in which gastric acids attack the esophagus and for which commonly prescribed medications, such as atropine, have serious adverse side effects.
From this evidence, many researchers have concluded that pharmacological modulation of the endogenous cannabinoid system provides new treatment options for a number of gastrointestinal diseases, including nausea and vomiting, gastric ulcers, irritable bowel syndrome, Crohn’s disease, secretory diarrhea, paralytic ileus and gastroesophageal reflux disease. The experience of patients with these GI disorders shows that for broad-spectrum relief, cannabis is highly effective and frequently helps when other treatment options prove ineffective.
Ingest the cannabis, for the best control of GERD, or use a vaporizer to remove the toxins and decrease the effects of the smoking on your condition. May 2003 Journal of Physiology showed that THC reduced acid reflux. Again, this was the use of purified THC .
Use a vaporizer, edibles (made from hash), tinctures and extracts (made with glycerin), tea, cannabutter
Indica x Sativa hybrid
AK 47, Master Kush, Purple Kush, Strawberry Cough, Blue Dream, Black Domina, Skywalker OG, Herijuana
1. DeVault KR, Castell DO (1999). "Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. The Practice Parameters Committee of the American College of Gastroenterology". Am J Gastroenterol 94 (6): 1434–42.doi:10.1111/j.1572-0241.1999.1123_a.x. PMID 10364004.
2. "The saliva PH test and cancer". Healingdaily.com. Retrieved 2009-08-19.
3. a b c Kahrilas, PJ (2008). "Clinical practice. Gastroesophageal reflux disease.". New England Journal of Medicine. 359 (16): 1700–7.doi:10.1056/NEJMcp0804684. PMID 18923172.
4. a b Wang KK, Sampliner RE (March 2008). "Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus". Am J Gastroenterol 103 (3): 788–97.doi:10.1111/j.1572-0241.2008.01835.x. PMID 18341497.
5. "Consumer Health Information". Healthlink.mcw.edu. Retrieved 2009-08-19.
6. "Spitting Up in Babies". familydoctor.org.
7. and Barrett's Esophagus. Retrieved on 2009-02-01.
8. Numans, ME; Lau, J; de Wit, NJ; Bonis, PA (April 2004). "Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics".Annals of internal medicine 140 (7): 518–27. PMID 15068979.
9. Diagnosis - Endoscopy. Retrieved on 2009-03-20.[dead link]
10. Mills, S (ed.) 2009.Sternberg's Diagnostic Pathology. 5th Edition.ISBN 978-0-7817-7942-5
11. Sontag S (1999). "Defining GERD". Yale J Biol Med 72 (2-3): 69–80.PMC 2579007. PMID 10780568.
12. a b Piesman M, Hwang I, Maydonovitch C, Wong RK (2007). "Nocturnal reflux episodes following the administration of a standardized meal. Does timing matter?". Am J Gastroenterol 102(10): 2128–34. doi:10.1111/j.1572-0241.2007.01348.x.PMID 17573791.
13. Ayazi S, Crookes PF, Peyre CG, et al. (2007). "Objective documentation of the link between gastroesophageal reflux disease and obesity". Am J Gastroenterol 102 (S2): 138–9.doi:10.1111/j.1572-0241.2007.01491_1.x.
14. Ayazi S, Hagen JA, Chan LS, et al. (August 2009). "Obesity and gastroesophageal reflux: quantifying the association between body mass index, esophageal acid exposure, and lower esophageal sphincter status in a large series of patients with reflux symptoms". J. Gastrointest. Surg. 13 (8): 1440–7. doi:10.1007/s11605-009-0930-7. PMC 2710497. PMID 19475461.
15. Morse CA, Quan SF, Mays MZ, Green C, Stephen G, Fass R (2004). "Is there a relationship between obstructive sleep apnea and gastroesophageal reflux disease?". Clin. Gastroenterol. Hepatol. 2(9): 761–8. doi:10.1016/S1542-3565(04)00347-7.PMID 15354276.
16. Kasasbeh A, Kasasbeh E, Krishnaswamy G (2007). "Potential mechanisms connecting asthma, esophageal reflux, and obesity/sleep apnea complex—a hypothetical review". Sleep Med Rev11 (1): 47–58. doi:10.1016/j.smrv.2006.05.001. PMID 17198758.
17. H.J. O'Connor (Feb 1999). "Helicobacter pylori and gastro-oesophageal reflux disease-clinical implications and management".Aliment Pharmacol Ther 13 (2): 117–27. doi:10.1046/j.1365-2036.1999.00460.x. PMID 10102940.
18. El-Omar E, Oien K, Nujuni AE, et al. (1997). "Helicobacter pylori infection and chronic gastric acid hyposecretion". Gastroenterology113 (1): 15–24. doi:10.1016/S0016-5085(97)70075-1.PMID 9207257.
19. C.A. Fallone, A.N. Barkun, S. Mayrand, G. Wakil, G. Friedman, A. Szilagyi, C. Wheeler & D. Ross (2004). "There is no difference in the disease severity of gastro-oesophageal reflux disease between patients infected and not infected with Helicobacter pylori". Aliment Pharmacol Ther 20 (7): 761–8. doi:10.1111/j.1365-2036.2004.02171.x. PMID 15379836.
20. "Lifestyle Changes to Manage Your Heartburn" WebMD
21. http://www.medscape.com/viewarticle/536343[dead link]
22. a b Kaltenbach T, Crockett S, Gerson LB (2006). "Are lifestyle measures effective in patients with gastroesophageal reflux disease? An evidence-based approach". Arch. Intern. Med. 166 (9): 965–71.doi:10.1001/archinte.166.9.965. PMID 16682569.
23. Decktor DL, Robinson M, Maton PN, Lanza FL, Gottlieb S (1995). "Effects of Aluminum/Magnesium Hydroxide and Calcium Carbonate on Esophageal and Gastric pH in Subjects with Heartburn". Am J Ther 2 (8): 546–52. doi:10.1097/00045391-199508000-00006.PMID 11854825.
24. Khoury, RM; Camacho-Lobato L, Katz PO, Mohiuddin MA, Castell DO (1999). "Influence of spontaneous sleep positions on nighttime recumbent reflux in patients with gastroesophageal reflux disease".Am J Gastroenterol 94 (8): 2069–73. doi:10.1111/j.1572-0241.1999.01279.x. PMID 10445529.
25. a b Tran T, Lowry A, El-Serag H (2007). "Meta-analysis: the efficacy of over-the-counter gastro-oesophageal reflux disease drugs". Aliment Pharmacol Ther 25 (2): 143–53. doi:10.1111/j.1365-2036.2006.03135.x. PMID 17229239.
26. Cash, B.D.; Chey, W.D.. "Role of Serotonergic Agents in Primary Chronic Constipation: Serotonergic Agents and Chronic Constipation". MedScape. p. 4. Retrieved 2009-09-07.
27. Fass, Ronnie. "Medical Management of GERD". MedScape. Retrieved 2011-02-18.
28. van Marrewijk CJ, Mujakovic S, Fransen GA, Numans ME, de Wit NJ, Muris JW, van Oijen MG, Jansen JB, Grobbee DE, Knottnerus JA, Laheij RJ (January 2009). "Effect and cost-effectiveness of step-up versus step-down treatment with antacids, H2-receptor antagonists, and proton pump inhibitors in patients with new onset dyspepsia (DIAMOND study): a primary-care-based randomised controlled trial".The Lancet 373 (9659): 215–25. doi:10.1016/S0140-6736(09)60070-2. PMID 19150702.
29. Abbas A, Deschamps C, Cassivi SD, et al. (2004). "The role of laparoscopic fundoplication in Barrett's esophagus". Annals of Thoracic Surgery 77 (2): 393–6. doi:10.1016/S0003-4975(03)01352-3. PMID 14759403.
30. Grant AM, Wileman SM, Ramsay CR, et al. (2008). "Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease: UK collaborative randomised trial". BMJ337: a2664. doi:10.1136/bmj.a2664. PMC 2603580.PMID 19074946.
31. Wileman, SM; McCann, S; Grant, AM; Krukowski, ZH; Bruce, J; Wileman, Samantha M (2010). "Medical versus surgical management for gastro-oesophageal reflux disease (GORD) in adults.". Cochrane database of systematic reviews (Online) 3 (3): CD003243.doi:10.1002/14651858.CD003243.pub2. PMID 20238321.
32. "New Surgery For Acid Reflux Sufferers". CBS Interactive Inc. January 16, 2009. Retrieved 2009-09-07.
33. Mahadevan U, Kane S (July 2006). "American gastroenterological association institute medical position statement on the use of gastrointestinal medications in pregnancy". Gastroenterology 131 (1): 278–82. doi:10.1053/j.gastro.2006.04.048. PMID 16831610.
34. Ruigomez A, Garcia Rodriguez LA, Wallander MA, et al. (September 2006). "Comparison of gastro-oesophageal reflux disease and heartburn diagnoses in UK primary care". CMRO 22 (9): 1661-8.doi:10.1185/030079906X120986. PMID 16968569. Lay summary.
35. Kotzan J, Wade W, Yu HH (September 2001). "Assessing NSAID prescription use as a predisposing factor for gastroesophageal reflux disease in a Medicaid population". Pharm Res 18 (9): 1367-72.doi:10.1023/A:1013010616496. PMID 11683254. Lay summary.
36. Fedorak RN, Veldhuyzen van Zanten S, Bridges R (July 2010). "Canadian Digestive Health Foundation Public Impact Series: Gastroesophageal reflux disease in Canada: Incidence, prevalence, and direct and indirect economic impact". Canadian Journal of Gastroenterology 24 (7): 431-4. PMID 20652158. Lay summary.
2. American College of Gastroenterology
P.O. Box 342260
Bethesda, MD 20827–2260
3. American Gastroenterological Association
4930 Del Ray Avenue
Bethesda, MD 20814
4. International Foundation for Functional Gastrointestinal Disorders
P.O. Box 170864
Milwaukee, WI 53217–8076
Phone: 1–888–964–2001 or 414–964–1799
5. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition
P.O. Box 6
Flourtown, PA 19031
12. Joy JE, Watson SJ, Benson JA Jr, (1999). Marijuana and medicine: Assessing the science base. Washington, DC: Institute of Medicine.
13. Croci T et al (2003). Role of cannabinoid CB1 receptors and tumor necrosis factor-alpha in the gut and systemic anti-inflammatory activity of SR 141716 (rimonabant) in rodents. Br J Pharmacol. Sep;140(1):115-22. Epub 2003 Jul 29.
14. Izzo AA et al (2001). Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation. Br J Pharmacol. Oct;134(3):563-70.
15. Dajani EZ et al (1999). 1′,1′-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid: a novel, orally effective cannabinoid with analgesic and anti-inflammatory properties. J Pharmacol Exp Ther. Oct;291(1):31-8.
16. Kulkarni-Narla A, Brown DR (2000). Localization of CB1-cannabinoid receptor immunoreactivity in the porcine enteric nervous system. Cell Tissue Res. Oct;302(1):73-80.
17. Coutts AA et al (2002). Localisation of cannabinoid CB(1) receptor immunoreactivity in the guinea pig and rat myenteric plexus. J Comp Neurol. Jul 8;448(4):410-22.
18. Westfall RE et al (2006). Survey of medicinal cannabis use among childbearing women: patterns of its use in pregnancy and retroactive self-assessment of its efficacy against ‘morning sickness’. Complement Ther Clin Pract. Feb;12(1):27-33. Epub 2005 Dec 22.
19. Gierenger D (1996). “Review of Human Studies on the Medical Use of Marijuana”. www.canorml.org.
20. Beal JE et al (1995). Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Journal of Pain & Symptom Management, 10, 89-97 .
21. Foltin R et al (1988). Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory, Appetite 11: 1-14.
22. Foltin R et al (1986). Behavioral analysis of marijuana effects on food intake in humans, Pharmacology, Biochemistry and Behavior 25: 577-582.