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Review: The Role of Cannabinoids on Esophageal Function—What We Know Thus Far 1 Department of Gastroenterology, Temple University Hospital, Philadelphia, Pennsylvania. 2 Lewis Katz School of Can CBD Help With GERD? Gastroesophageal reflux disorder (GERD) is caused by esophageal dysfunction and unregulated gastric acid secretion. CBD for Acid Reflux has been found to be effective as per recent research. Using CBD oil for acid reflux helps alleviate symptoms like pain and inflammation.

Review: The Role of Cannabinoids on Esophageal Function—What We Know Thus Far

1 Department of Gastroenterology, Temple University Hospital, Philadelphia, Pennsylvania.

2 Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.

Rahul Kataria

1 Department of Gastroenterology, Temple University Hospital, Philadelphia, Pennsylvania.

2 Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.

Ron Schey

1 Department of Gastroenterology, Temple University Hospital, Philadelphia, Pennsylvania.

2 Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.

* Address correspondence to: Ron Schey, MD, FACG, Department of Gastroenterology, Temple University Hospital, Philadelphia, PA 19140, E-mail: [email protected]

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The endocannabinoid system (ECS) primarily consists of cannabinoid receptors (CBRs), endogenous ligands, and enzymes for endocannabinoid biosynthesis and inactivation. Although the presence of CBRs, both CB1 and CB2, as well as a third receptor (G-protein receptor 55 [GPR55]), has been established in the gastrointestinal (GI) tract, few studies have focused on the role of cannabinoids on esophageal function. To date, studies have shown their effect on GI motility, inflammation and immunity, intestinal and gastric acid secretion, nociception and emesis pathways, and appetite control. Given the varying and sometimes limited efficacy of current medical therapies for diseases of the esophagus, further understanding and investigation into the interplay of the ECS on esophageal health and disease may present new therapeutic modalities that may help advance current treatment options. In this brief review, the current understanding of the ECS role in various esophageal functions and disorders is presented.

Overview of Endocannabinoid System

The endocannabinoid system (ECS) primarily consists of cannabinoid receptors (CBRs), endogenous ligands, and enzymes for endocannabinoid biosynthesis and inactivation. 1 The ECS plays an important role in regulation of synaptic transmission in the central and enteric nervous systems (ENS) through both excitatory and inhibitory effects, mediating a variety of physiological processes including pain sensation and modulation, motor function, inflammation, and immunity. 2

CBRs belong to the superfamily of G-protein-coupled receptors and are expressed in two main forms, CB1 and CB2. 3 CB1 is mainly expressed in central and peripheral neurons, including the ENS, whereas CB2 is mostly expressed by inflammatory/immune cells. 4–6 The ubiquitous distribution of CBRs in the ENS and gastrointestinal (GI) tract highlights its role in GI health and disease including motility, inflammation and immunity, intestinal and gastric acid secretion, nociception and emesis pathways, and appetite control 7–9 ( Table 1 ).

Table 1.

Known Functions of the Endocannabinoid System Along the Upper Alimentary Tract

Function Brief summary Related studies
Appetite regulation 1. Stimulates appetite, especially high energy, fatty foods Argueta and DiPatrizio 18
2. Induces hyperphagia, potential target for obesity therapy, generates hunger signal DiPatrizio et al. 17
DiPatrizio et al. 16
Nociception/emesis 1. Stimulation of CB1 receptor in CNS leads to nausea, therapeutic target for antiemetic effect of exogenous cannabinoid therapy Van Sickle et al. 19
Rock and Parker 71
Motility 1. Multiple receptors (CB1 and CB2) thought to influence contractile and relaxant forces in stomach Hornby and Prouty 10
2. Modulates intestinal propulsion, GPR55 inhibits whole gut transit time, modulation of cholinergical and vagal stimulation of upper GI tract Yuece et al. 12
Storr et al. 21
3. Enhances gut motility in setting of inflammation Izzo et al. 24
Yang et al. 26
Li et al. 27
Gastric acid and intestinal secretions 1. Exhibits antisecretory effects on gastric acid Adami et al. 15
2. Implicated in mitigating inflammation and mucosal damage in GERD Calabrese et al. 25
3. Effect on transient lower esophageal relaxation Lehmann et al. 33
Inflammation and immunity 1. Anti-inflammatory effects in esophageal reflux disease Calabrese et al. 25
2. CB2 receptor downregulates inflammation and associated hypermotility in disease state Izzo 23
Analgesia 1. Increases pain threshold Clapper et al. 65
Malik et al. 66

CNS, central nervous system; GERD, gastroesophageal reflux disease; GI, gastrointestinal; GPR55, G-protein receptor 55.

The CB1 receptor plays a role in intestinal motility by attenuating both large and small bowel muscle tone when activated. 10–13 Within the upper GI tract, activation of CB1 decreases intragastric pressure and delays gastric emptying through inhibition of excitatory neurons. 14,15 As demonstrated in rodent models, CB1 receptors play a role in energy regulation by driving consumption of food high in dietary fat. 16 After sham feeding in rats with high-fat foods, upregulation of CB1 receptors was found in rat small intestine, leading to inhibition of neural signaling events of satiety to suppress feeding. These findings suggest that CB1 acts through a positive feedback loop after dietary fat exposure to stimulate further consumption of higher energy foods. In another study, pharmacological inhibition of CB1 led to decreased amount of refeeding in rats after food deprivation, highlighting CB1 receptor’s role in appetite regulation. 17 In addition, CB1 was found to be upregulated in rats fed a high fat, high caloric Western diet (WD). It was also suggested to play a role in hyperphagia after antagonism of CB1 with an inhibitor led to decreased food intake in rats fed a WD for 60 days. 18

CB2 receptors located in the central nervous system (CNS) have been shown to play a role in the emetic pathway; however, the receptor has also been found in inflammatory tissue and immune cells (plasma cells and macrophages) throughout the GI tract. 19–22 CB2 is expressed in the GI tract but less extensively than CB1 receptors. 23 Evidence that upregulation of CB2 receptors occurs in patients with inflammatory bowel disease suggests that these receptors play a critical role in colonic inflammation. 7 Distinct from CB1 receptors effect on motility, CB2 receptors may further regulate motility in pathophysiological states with its expression being upregulated in inflammatory disease states. 5,24

Presence of CBRs in human esophageal epithelium was first demonstrated in a study comparing patients with nonerosive esophageal reflux disease (NERD) and erosive esophageal reflux disease (ERD) to normal controls. 25 The authors found increased expression of CB1 mRNA in NERD patients compared with erosive esophagitis, but overall less expression compared with normal controls. Interestingly, CB1 protein expression was similar to patients with ERD, whereas NERD patients showed increased CB1 receptor levels when compared with healthy controls ( Fig. 1 ). Although other GI inflammatory conditions have increased CB1 activity, there may be contribution of the inflammatory microenvironment that alters CB1 gene expression. 24

Immunostaining of CB1 receptor in histological sections of esophageal mucosa. Healthy subjects (a) show a weak positive staining localized in mature squamous cells (black arrow) and in connectival papillae (red arrows). NERD patients (b) show CB1 receptor expression in mature squamous cells (black arrow), in squamous cells (blue arrow), and in connectival papillae (red arrow). ERD patients (c) show CB1 positivity only in mature squamous cells (black arrow) and in squamous cells (blue arrows), whereas connectival papillae appear negative (red arrow). CB1 staining disappeared in esophageal mucosa (d) when CB1 blocking peptide was incubated with CB1 antibody. ERD, erosive esophageal reflux disease; NERD, nonerosive esophageal reflux disease. Reprinted with permission from Calabrese et al. 25

Recently, a potential third CBR has been identified with implications in the GI tract. G-protein receptor 55 (GPR55) shares 13–15% sequence homology with the CB1 and CB2 receptors and responds to a multitude of endogenous and exogenous cannabinoid ligands as well as several lipids. 26 A recent study found activation of GPR55 after administration of a synthetic agonist slowed down whole-gut transit in mice in vivo, suggesting GPR55 may be involved in the regulation of gut motility. 27

Endocannabinoids are endogenously produced ligands that exert effects on CBRs. The major ligands, anandamide (AEA) and 2-arachidonylglycerol (2-AG), play a role in maintaining GI homeostasis and have been found at increased levels in GI disease states, including celiac disease, diverticulosis, and colorectal cancer. 28–30 Exogenous cannabinoids, both plant-derived phytocannabinoids (cannabis sativa) and synthetic cannabinoids, also directly activate CBRs. They have been shown to play a role in both GI pathophysiology (e.g., cannabinoid hyperemesis syndrome) and therapies (e.g., antiemetics and appetite stimulant). 31

Although both CB1 and CB2 receptors have been found in the esophagus, few studies have focused on the role of cannabinoids on esophageal function. 21 Thus far, the role of GPR55 in esophageal motility has not been established. Given the varying and sometimes limited efficacy of current medical therapies for diseases of the esophagus, further understanding and investigation into the interplay of the ECS on esophageal health and disease may present new therapeutic modalities that may help advance current treatment options. In this review, the current understanding of the role of ECS in various esophageal functions and disorders is presented.

Swallowing Mechanism

The swallowing reflex is an important mechanism in controlling acid exposure in the esophagus, whereby increased swallowing decreases stasis and reduces acidic and nonacidic reflux. The role of the swallowing reflex in reducing reflux has been demonstrated after observation that supine sleeping patients experienced a decreased spontaneous swallowing reflex during 24-h pH monitoring, leading to increased acid and nonacid exposure. 32 CB1 receptor activation has been shown to decrease spontaneous swallows in human and animal studies. One study on dogs found administration of CB1 agonist suppressed spontaneous swallowing in a dose-dependent manner with an >80% decrease in spontaneous swallows at high doses (57 nmol/kg). 33 The authors noted that although administration of CB1 agonist decreased transient lower esophageal sphincter relaxations (TLESRs) thereby decreasing reflux events, the concomitant decrease in spontaneous swallows and clearance of refluxate potentially limit the benefits of decreasing TLESRs. The mechanism of action of CBRs on swallowing mechanism is likely centrally located through endogenous cannabinoid action, modifying synaptic neurotransmitter release. 34 The swallowing reflex, evoked by repetitive electrical stimulation of the superior laryngeal nerve in rats, was analyzed with and without combinations of both CB1 and CB2 agonists and antagonists. CB1 receptor antagonist injected directly into the nuclear tractus solitarius blocked the action of intravenous-administered CB1 agonist. The only study in humans to date found administration of the combination CB1/CB2 agonist Δ9-THC resulted in a significant reduction in the number of swallows wherein high doses (20 mg) led to a reduction in spontaneous swallows by 50%. 35

Esophageal Motility

CBRs, specifically CB1, play a role in GI motility and have mainly been studied in the small intestine and colon. 8,10 Only two studies have evaluated the effect of ECS on esophageal motility in humans. 35,36 Administration of Δ9-THC decreased basal lower esophageal sphincter (LES) pressure in a nondose-dependent manner, with onset occurring 45 min after meal ingestion, maximal effect around 100 min, followed by slow recovery. 35 This was confirmed in another human study that administration of rimonabant, a CB1 receptor antagonist, increased postprandial LES pressures in the first and second postprandial hours. 36

Previous studies in animal models did not demonstrate CBR action influenced esophageal motility. Lehman et al. demonstrated that CBR agonism did not influence the extent of LES relaxation. Similarly, CBR antagonists had no influence on esophageal peristalsis. 33 A recent case report suggested that exogenous phytocannabinoid use improved symptoms of dysphagia in a patient with manometric findings, consistent with type 3 achalasia. 37 Others have suggested that exogenous cannabinoid use, like chronic opiate use, may produce motor findings similar to type 3 achalasia. 38 The conflicting data support the need for further study of endo- and exogenous cannabinoids on esophageal motility. 39

Gastroesophageal Reflux Disease and TLESRs

TLESRs are the predominant mechanism seen in gastroesophageal reflux disease (GERD). TLESRs occur after gastric stimuli, mainly distension, to relieve counteracting gastric pressure on the LES. 40,41 The LES response to gastric distension is vagally mediated through communication of the LES and crural diaphragm with afferent gastric pathways, brainstem integrative centers (nucleas tractus solitarus and dorsal motor nucleus), and efferent inhibitory pathways. 41 The action of CBRs on TLESRs and GERD was first demonstrated in animal models after the observation that administration of a CB1 agonist (WIN55,212-2) reduced the rate of TLESRs without altering the TLESRs latency or esophageal peristalsis. 33 The authors concluded that the action of the CBRs on TLESRs most likely occured via central pathways because no effect on the extent of LES relaxation was seen. 33,42,43 Absence of CB1 receptors in preganglionic vagal motor neurons projecting to the gastric fundus or LES further supports the assumption that CB1 does not directly participate in vagal motor output modulation and rather relies on central activation. 42

Interestingly, the use of a CB1 receptor antagonist (rimonabant) in healthy human subjects enhanced postprandial LES pressure but unexpectedly decreased TLESRs. 36 This contradicts earlier data in an animal model with dogs that showed rimonabant enhanced the rate of TLESRs and reflux events that received acidified meal and intragastric air insufflation. 36 The authors attributed this discrepancy to different dosage, bioavailability, or interspecies differences of rimonabant. A possible explanation for the similar results from administrating CBR antagonist and agonists may be a result of rimonabant exerting potent CB1 receptor-independent pharmacological effects. 44

Gastric accommodation may affect TLESRs and play an important role in development of GERD. 45 Previous studies evaluated the effect of CB1 receptors on pain sensation during intragastric balloon distension, however, they did not find modulation of CB1 receptors with rimonabant-influenced mechanosensitivity of the proximal stomach. 46 It should be noted that baclofen has been shown to decrease TLESRs rate and increase basal LES pressure while not affecting meal-induced fundic accommodation, suggesting that the mechanism may not be as simple as binary, an observation previously suggested by Lehmann et al. 33 Other studies have suggested that using Δ9-THC inhibits gastric insufflation-induced LES relaxations in the decerebrate ferret, highlighting the need for further clarification of the relationship between gastric stimulation and TLESRs. 10

The effect of CBRs on gastric emptying has been studied in humans although the data are limited and conflicting. 48–51 Although there may be some influence of CBRs, gastric emptying itself does not necessarily correlate with fundus accommodation and activation of TLESRs.

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The presence of CBRs in the esophagus, specifically those affecting TLESRs, offers a potential therapeutic target for treating GERD. Using Δ9-THC, Beaumont et al. demonstrated decreased rate of TLESRs in healthy volunteers who received 10 and 20 mg of Δ9-THC on three occasions a week apart. 35 Delta(9)-THC significantly reduced the number of TLESRs and caused a nonsignificant reduction of acid reflux episodes in the first postprandial hour. In addition, lower esophageal sphincter pressure and swallowing were significantly reduced by Δ(9)-THC. 35 However, in the high dose of Δ9-THC (20 mg) group, central activity led to increased nausea and vomiting. Centrally acting CB1 receptor agonists produce the psychotropic effects and, therefore, selective targeting of peripheral CB1 receptors is necessary for effective therapy, with recent efforts to develop higher potency and effective CB1 agonists. 52,53 Previous studies have looked at using CB1 antagonists; however, their therapeutic use is also limited by its side effect of major depression. 54

Newer methodologies for understanding the pharmacodynamics and pharmacokinetics of medication effects on TLESRs have been developed that may provide more accurate modeling of drug concentrations and their effects. 55

Bronchoconstriction

In patients with a chronic cough where lung disease, environmental exposure, and medications have been excluded, GERD is often a major cause. 56 The two main mechanisms implicated in reflux-related cough are microaspiration of refluxate and stimulation of vagal innervation of the esophagus, leading to esophagobronchial reflex arc. The CB2 receptor has been shown to play a role in inhibiting bronchoconstriction and microvascular leakage in reflux models using guinea pigs. After infusion of intraesophageal HCl, the inhibitory effect of bronchoconstriction by a CB1 agonist (WIN55,212-2) was blocked after administration of a CB2 antagonist (SR 144528) but not after CB1 receptor antagonist, demonstrating CB2 receptor’s role as a downregulatory mechanism of sensory nerve activation. 57 CB2 receptor activation in models of direct airway damage has been shown to play an active role in reducing inflammation, potentially supporting protective role of CB2 in microaspiration of refluxate. 58

Visceral Hypersensitivity and Pain

Functional esophageal disorders are defined as the presence of esophageal symptoms in the absence of structural, inflammatory, or motor abnormalities. 59 Proposed pathophysiological mechanisms include alterations in neural processing between peripheral triggers and central perception of esophageal symptoms. 60 CBRs likely play a role in pain sensation and modulation through visceral antinociceptive action. 61 Previous studies have demonstrated an analgesic effect of cannabinoids in animal models through both CB1 and CB2 activation. 62–64 In one important study, upregulation of the endocannabinoid AEA through inhibition of its degrading enzyme led to an attenuated behavioral response to noxious stimuli in rodents. 65 This suggests a central role of CB1 receptors in mitigating pain-related inputs to the CNS.

There are few studies of visceral sensitivity in the esophagus and the effects of CBR modulation. In a randomized, placebo controlled trial, administration of dronabinol for 1 month increased the threshold for first sensation, pain frequency, and intensity of pain during an esophageal balloon distention test. 66 Notably, anxiety and depression indices were unchanged after dronabinol administration. The mainstay of functional esophageal disorders relies on tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors, all of which have been found to influence psychiatric parameters, highlighting a possible difference in mechanism of action. 60

Role in Esophageal Neoplasm

Cannabinoids inhibit tumor cell growth and induce apoptosis by modulating cell signaling pathways. 67 Decreased frequency of CNR-1 gene, the gene encoding CB1 receptor, expression was found in tissue of esophageal cancer patients (10.8%) compared with controls (60.0%), and its presence is considered an independent predictor of survival. 68 However, recently a multivariate analysis revealed that CB1 receptor overexpression was independently associated with poor prognosis (p=0.019). Biological analysis of CB1 receptor overexpression using esophageal squamous carcinoma cell lines revealed that CB1 receptor activation appeared to promote cell proliferation and invasion. 69 Thus, the role of CB1 receptor expression in tumorogenesis needs to be further evaluated.

Conclusion

A more thorough understanding of the ECS in esophageal function and disease is needed. Recently, there has been a push to legalize cannabis for both medicinal and recreational use. There have also been reports of increasing use of both plant-derived cannabis and synthetic cannabinoids in the United States. 70 This may allow additional studies to be added to the few human studies to date on the effect of cannabinoid use in humans. Further study in this area is imperative for the development of future therapeutic potential of utilizing the ECS.

Authors’ Contributions

J.G. was involved in literature review and is the primary author. R.K. was involved in literature review. R.S. was involved in study conceptualization and reviewed the article.

Abbreviations Used

CBRs cannabinoid receptors
CNS central nervous system
ECS endocannabinoid system
ENS enteric nervous system
ERD erosive esophageal reflux disease
GERD gastroesophageal reflux disease
GI gastrointestinal
GPR55 G-protein receptor 55
NERD nonerosive esophageal reflux disease
THC tetrahydrocannabinol
TLESRs transient lower esophageal sphincter relaxations
WD Western diet

Author Disclosure Statement

No competing financial interests exist.

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Cite this article as: Gotfried J, Kataria R, Schey R (2017) Review: the role of cannabinoids on esophageal function: what we know thus far, Cannabis and Cannabinoid Research 2:1, 252–258, DOI: 10.1089/can.2017.0031.

CBD Oil for GERD – August 2022

Frequent acid reflux can lead to gastroesophageal reflux disease ( GERD ). This condition is caused by stomach contents flowing back into the esophagus and the mouth.

Common symptoms of GERD include heartburn ( burning sensations in the chest), voice hoarseness, sore throat, coughing, and wheezing.

Over-the-counter medications that can treat GERD include antacids ( stomach acid neutralizer) and proton pump inhibitors (PPI), such as cimetidine and nizatidine (acid reducers).

However, these medications might produce adverse effects, such as nausea, vomiting, constipation, stomach pain, and neurotoxicity. Usually, these side effects were observed among elderly patients (6) . These factors are why some individuals are turning to alternative treatments. They can also be very cost-prohibitive over the long-term.

Currently, there is a lack of direct studies on CBD ’s efficacy in treating GERD .

However, existing studies have shown that CBD ’s activity on cannabinoid receptors in the endocannabinoid system (ECS) might provide several modulatory effects on gastric acid production, GI inflammation, and esophageal function (7) .

The ECS, which maintains balance by regulating bodily functions, is present in all vertebrates and mammals.

A 2016 review posted in the Asian Pacific Journal of Medicine mentioned that cannabinoid receptor (CBR) activities caused by CBD and THC might reduce gastric acid secretions (8) .

In the review, the author cited studies demonstrating how Cannabis sativa extract protected animal subjects from mucosal damage and gastric lesions (9) .

Cannabis sativa (hemp) is a plant rich in cannabinoids such as CBD and THC (10) .

The author concluded that gastric protective and anti-inflammatory properties of cannabinoids might be useful in treating GERD and peptic ulcer disease (11) .

Lower esophageal sphincter ( LES ) dysfunction is the principal cause for GERD . The dysfunction may be brought by transient LES relaxation or LES pressure (12) .

A n animal study posted by the British Pharmacological Society mentioned that CBR activities might modulate GI motility by reducing LES relaxation (13) .

Some researchers believe that gastric motility abnormalities might also be linked to the onset of GERD (14) .

A review published by the British Journal of Pharmacology mentioned that CBR activities might modulate upper and lower GI motility (15) .

Moreover, GERD is often associated with inflammation and oxidative stress. Researchers mentioned that inflammatory cytokines might cause early inflammation of individuals with GERD (16) .

A study using animal and human biopsies have shown that CBD possesses anti-inflammatory and antioxidant effects (17) .

The authors added that these therapeutic benefits might be useful in treating GI inflammation conditions (18) .

A cross-study from the American Journal of Physiology also observed these benefits . The authors concluded that CBD ’s activity on ECS receptors might modulate gut motility and reduce inflammatory diseases (19) .

Additionally, esophageal leakage is the primary mechanism of reflux-related cough and constriction of airways in the lungs (bronchoconstriction) (20) .

The European Journal of Pharmacology published an animal study demonstrating how receptor activation might reduce microleakage that causes bronchoconstriction (21) .

Lastly, researchers mentioned that GERD could be a significant source of anxiety and depression. A clinical study published by Cureus concluded that out of 258 patients, 41.4% suffered from depression, 34.4% suffered from anxiety, and 27.13% suffered depression and anxiety (22) .

A study released by Frontiers in Immunology acknowledged that CBD might improve mental health due to its anxiolytic and antidepressant properties (23) .

How CBD Oil Works to Help With GERD

The endocannabinoid system (ECS) is studied for its role in maintaining homeostasis in the human body.

The ECS is composed of receptors that are spread across the human body. These receptors include the G-protein cannabinoid receptors , CB1 and CB2 (24) , and G-protein receptor 55 (GPR55) (25) .

These receptors can be found in the immune system, central nervous system , and gastrointestinal system (GI) (26) .

Researchers acknowledged that activating the CB1 and CB2 receptors in the ECS might influence bodily functions, resulting in potential therapeutic benefits (27) .

The presence of cannabinoid receptors in the GI system highlights the ECS’ role in modulating GI functions, health, gastric secretions, and inflammation (28) .

The CB1 receptor might have a role in modulating intestinal motility by reducing LES relaxation and promoting esophageal peristalsis (29) .

The author added that CB1 activation might reduce acid and intestinal fluid secretions (30) .

Aside from antisecretory effects , influencing of the ECS might also provide anti-inflammatory properties (31) .

CB2 is mostly distributed in the central nervous system . Researchers also found CB2 receptors in inflammatory tissues and cells in the gastrointestinal tract (32) .

Moreover, CB2 activation might further regulate GI tract motility and reduce the uptake of inflammatory diseases (33) .

Studies mention that CB2 activation might play a role in inhibiting microvascular leakage and bronchoconstriction on animal reflux models (34) .

A 2016 review mentioned that GPR55 might also be involved in GI motility. The authors indicated that the administration of a receptor agonist slowed down the gut transit in mice models (35) .

Modulatory effects can be triggered or stimulated by cannabinoids , such as cannabidiol ( CBD ), tetrahydrocannabinol ( THC ), cannabichromene (CBC), cannabinol (CBN), and cannabigerol (CBG) (36) .

There is evidence that CBD was able to activate GPR55 in an animal study published by the British Journal of Pharmacology ( 37) .

Moreover, even with its low affinity to CB1 and CB2, CBD might also influence how other cannabinoids trigger the receptors. This mechanism allows for receptors to reduce the expression of inflammatory cytokines (38) .

Cytokines are signaling proteins that modulate the body’s response to inflammation (39) .

Moreover, an in vivo study posted by the British Journal of Pharmacological attributed another cannabinoid , CBC, for its ability to reduce inflammation-induced hypermotility (40) .

The author continued that CBC’s ability to modulate GI motility warranted further studies on conditions, such as mucosal inflammation, gastric secretion, intestinal secretion, and visceral pain (41) .

Although existing studies acknowledged CBD ’s potential in influencing CBR activities, clinical trials are needed to prove CBD ’s efficacy on GERD symptoms .

The Pros and Cons of CBD Oil for GERD

The Pros
  • CBD might trigger CBR activities in the ECS system, thus, providing modulatory effects on the upper GI system (42) .
  • CBD might trigger CBR activities and help reduce gastric acid secretions (43) .
  • CBD might also trigger CBR activities and help decrease lower esophageal relaxation (44) .
  • A study concluded that gastric protective and anti-inflammatory properties of cannabinoids , such as CBD and THC , might be useful in treating GERD (45) .
  • CBD might help alleviate anxiety and depression of individuals suffering from GERD (46) .
  • CBD has been acknowledged to have an excellent safety profile for human consumption (47) .
The Cons
  • There are no direct studies on how CBD might help with GERD symptoms . All existing studies are focused on CBD ’s potential activities on ECS receptors that might help modulate GERD symptoms .
  • If used in high doses, CBD may cause side effects , such as drowsiness, loss of appetite, and dry mouth (48) .
  • A recent animal study discovered that CBD might cause hepatotoxicity (liver damage) (49) .

How CBD Oil Compares to Alternative Treatments for GERD

Some individuals may prefer drinking chamomile tea to soothe their digestive tract . Studies have acknowledged that flavonoids in chamomile flowers provide anti-ulcerogenic properties. The flavonoids might also reduce acid output (50) .

Another alternative treatment option is ginger tea. A clinical study from Food, Science, and Nutrition mentioned that ginger consumption led to improved GI motility. The authors also acknowledged ginger’s anti-inflammatory and anti-ulcer properties (51) .

Moreover, researchers acknowledged that deglycyrrhizinated licorice might alleviate acid reflux symptoms by suppressing acid production in the stomach (52) .

CBD might be similar to the alternative treatments mentioned due to its anti-inflammatory and acid-reducing properties (53) . CBD infused tea may also be taken instead of ginger or chamomile tea.

How to Choose the Best CBD Oil for GERD

The most recommended type of CBD oil for reducing GERD symptoms is full-spectrum .

Full-spectrum CBD oil contains all the major phytocannabinoids in hemp, such as CBD , CBC, CBG, CBN, and 0.3% THC . Together, these cannabinoids provide the individual with the “entourage effect.”

A review published in Frontiers in Plant Science mentioned that the entourage effect (or cannabis synergy) increased the primary activity of the endocannabinoid receptors (54) .

The author added that cannabis synergy helped explain why botanical medications display high efficacy compared to isolated compounds (55) .

The entourage effect was demonstrated by a controlled trial on patients with uncontrollable pain. In the study, THC -dominant opioid treatment failed to produce significant improvement compared to placebo (56) .

However, a whole-plant extract containing both THC and CBD produced remarkably better results (57) .

Broad-spectrum typically contains CBD , CBG, CBC, and CBN. Broad-spectrum is recommended for individuals who want to achieve the entourage effect without the presence of THC .

Lastly, individuals who cannot tolerate other cannabinoids may opt for CBD isolate. CBD isolate typically contains 99% pure CBD .

Additional tips to consider before buying CBD :

  • Individuals may find more information about the CBD product by checking customer reviews and testimonials.
  • Individuals with GERD must first consult with a gastroenterologist and discuss treatment options. Doctors may recommend prescription medications .
  • Individuals intolerant to prescription medications side effects must discuss their plan to use CBD with their doctors.

CBD Dosage for GERD

There is a lack of scientific studies on the appropriate dosage when using CBD for GERD .

However, there are existing dosing studies that observed CBD ’s therapeutic benefits on other health conditions.

The British Journal of Clinical Pharmacology shared a review that collected data from clinical population dosing studies.

The authors mentioned that a dose range of less than 1 to 50 milligrams per kilogram a day was used on various medical conditions , including chronic pain, anxiety, epilepsy, and many more (58) .

A study shared in Pharmacology and Pharmacy mentioned that CBD has a bell-shaped curve response. The authors observed that a limited dose range was enough to achieve CBD ’s therapeutic benefits (59) .

This hypothesis was supported by another study posted in the Frontiers of Pharmacology . The study experimented with dosages using healthy volunteers with public speaking anxiety (60) .

The study found that a dose of 300mg was able to reduce anxiety scores better than 100 mg and 900mg dosings (61) .

However, individuals must always be cautious when using CBD . A recent study shared by Molecules observed that extremely high CBD doses caused hepatotoxicity in rat models (62) .

How to Take CBD Oil for GERD

The recommended CBD administration for GERD is through oral or sublingual delivery.

Oral administration methods may be available through capsules, softgels, and gummies. These methods may be taken with or without a meal.

CBD tinctures may be used for sublingual administration. Individuals may use an applicator to put a few drops of CBD under the tongue. CBD tinctures may have an earthy taste due to terpenes (aromatic compounds).

Both oral and sublingual administration were observed to provide plasma concentrations that lasted three to four hours after intake (63) .

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Sublingual administration has also been observed to provide faster results when taken in a fasted state (empty stomach). However, high plasma concentrations were found when CBD is taken during a fed state (64) .

When using CBD for its pain-relieving properties, the recommended administration is through smoke or vapor inhalation. A quick delivery method is recommended for emergencies, such as heartburn .

A study posted by Biomedical and Environmental Mass Spectrometry shared that CBD inhalation can deliver plasma concentrations within three minutes (65) .

This evidence was supported by another study that acknowledged the lungs to be very efficient in delivering CBD into the bloodstream. The authors explained that vapor inhalation could deliver plasma concentrations within 10 minutes or less (66) .

However, individuals must be aware that smoke or vapor inhalation could have side effects , such as chest pain , shortness of breath, chemical irritation, and allergic reactions (67) . By and large, it is generally reasonable to assume that inhalation of volatile substances will cause some degree of pulmonary inflammation.

What Is the Difference Between Acid Reflux and GERD?

Acid reflux occurs when the LES muscle lets stomach acid flow back into the esophagus. This condition is caused by transient lower esophageal sphincter relaxations (TLESR).

The sphincter muscle opens when food is swallowed. During TLESR, the sphincter opens even when the individual is not swallowing. Gastric acid in the esophagus may lead to inflammation (esophagitis).

GERD is a more severe form of acid reflux disease . Similar to GERD , acid reflux symptoms include heartburn , coughing, and wheezing.

Untreated GERD may also cause esophageal mucosal damage (68) and hiatal hernia (69) brought by prolonged gastric acid exposure on the lining of the esophagus . Moreover, individuals with GERD have a higher risk of esophageal cancer.

Aside from OTC and prescription medication , surgical intervention is also an option to treat GERD .

Studies have shown that 40% of GERD patients do not respond to antacid and acid reducers. Thus, some individuals opt for the anti-reflux laparoscopic procedure to improve their quality of life (70) .

However, GERD patients must meet qualifying criteria before they are considered for the procedure.

Risk Factors and Other Causes of GERD

Some lifestyle factors may contribute to the prevalence of GERD symptoms and cause further irritation to the esophagus. Risk factors and causes include:

  • Eating large meals, spicy foods, and fatty foods
  • Eating late at night
  • Smoking
  • Drinking alcoholic beverages and coffee
  • Taking aspirin
  • Obesity
  • Pregnancy
  • Hiatal hernia (bulging of the stomach)

How Is CBD Oil Different From Medical Marijuana?

CBD oil is extracted from Cannabis sativa (hemp) using CO 2 , steam, or a solvent. The extraction’s purpose is to create a concentrated version of Cannabis sativa . The cannabinoid concentrations can be added into carrier oils, edibles, capsules, and vape juice.

Also, the extraction methods allow the manufacturers to control the amount of THC .

In the United States, CBD products are prohibited from having more than 0.3% THC in the concentration.

In medical cannabis or marijuana, the plants are harvested and dried. Recreational and medicinal marijuana use is only legal in 11 US states (71) , while CBD is legal in all US states and territories (72) .

However, CBD remains unregulated. Brands are not held accountable for inconsistent cannabinoid concentrations. Thus, individuals are advised to research before buying CBD products .

Legitimate CBD brands provide customers with a certificate of analysis (COA). The COA is a third-party test result produced by ISO certified laboratories. The lab test for cannabinoid concentrations and the presence of harmful chemicals, such as heavy metals, pesticides, microbial, and fungal contaminants.

The COA is the determining factor if the product is safe for human and animal consumption.

Conclusion

Studies acknowledged that CBD might influence gastric production by triggering receptors in the ECS system. This activity might help in alleviating acid reflux symptoms (73) .

CBD ‘s receptor activities might help modulate the esophageal function and prevent gastric acid leakage into the esophagus (74) .

Moreover, cannabinoids , such as CBD and CBC, have been shown to possess gastric protective and anti-inflammatory properties that might alleviate GERD symptoms (75) .

CBD has also been acknowledged for its ability to reduce anxiety and depression (76) .

However, more clinical studies are needed to support CBD ’s efficacy in treating GERD .

Whatever treatment is chosen, one must make the necessary lifestyle changes to alleviate GERD symptoms .

CBD for Acid Reflux and GERD – Is It Effective?

If you are reading this post, you (or someone you know) likely experience a burning sensation in the chest or throat, especially after eating spicy food.

You have tried the traditional treatments of acid reflux or GERD and have not seen the expected results. It’s also possible you have heard about the benefits of CBD use and are wondering whether it can help with your acid reflux symptoms.

Luckily you have found this post. Here we look at everything you need to know about CBD for acid reflux and GERD. We will also learn how using CBD oil for acid reflux provides relief from its symptoms.

Let’s get started:

Table of Contents

How is Acid Reflux Caused? Is CBD for Acid Reflux Beneficial?

The gastrointestinal system is a sensitive organ in your body. When your digestive network is interfered with, it may lead to acid reflux (the acid stomach backflow).

Acid reflux happens when the stomach acid moves into your esophagus when the lower esophageal sphincter (LES), which is supposed to close when food passes through, fails to close or opens more often.

As such, the acid produced by your stomach moves up into the esophagus leading to unpleasant symptoms, including:

  • Heartburn (burning chest discomfort)
  • Regurgitation
  • Dysphagia
  • Bloating
  • Burping
  • Nausea
  • Hiccups
  • Dry cough, wheezing, or hoarseness

Drinking coffee, taking a hearty meal, or alcohol consumption can cause heartburn in people with acid reflux. Many people commonly experience acid reflux in the morning that causes lots of discomforts.

What’s the Difference Between Acid Reflux and GERD?

Although acid reflux and gastroesophageal disease are related, the terms mean different things.

As earlier stated, acid reflux happens when stomach acid flows back into the esophagus resulting in heartburn. Usually, this occurs after taking spicy meals or drinking coffee or alcohol.

GERD occurs when you have a more severe form of reflux with symptoms of severe acid reflux . Heartburn is the most common symptom of GERD (more than two times a week). Other GERD symptoms include difficulty swallowing, chest pain. Regurgitation of sour liquid, and coughing.

As you can see, acid reflux and GERD exhibit the same symptoms, but the symptoms occur more than twice a week in people with GERD.

CBD Reflux Benefits – Demand in the Global Market

As of 2019, the global cannabis legal market was valued at 17.7 billion U.S. dollars. It is expected that the market will be worth 73.6 billion U.S. dollars by 2027.

Gerd and Marijuana health benefits and the continued legalization in various countries are the major drivers of this vast market.

We have seen the emergence of many CBD brands to cater to the increasing cannabis demand. If you plan to invest in the CBD industry, it is imperative to work with a reputable CBD marketing agency .

The best CBD marketing agency understands the industry trends and will use their expertise to put your business before your target market without being at loggerheads with authorities.

CBD for Acid Reflux and GERD

Before we look at the benefits of CBD for GERD , let’s take a closer look at the Endocannabinoid System (ECS) and its role in our bodies.

The ECS plays a vital role in your wellbeing and regulates many biological functions including, sensations, memory, anti-secretory effects, and pain perception.

Cannabinoids (found in the cannabis plant and those found in the body) play a vital role in gastric and intestinal acid secretion and regulate gastrointestinal motility.

CBD reacts with the endocannabinoid system and may reduce the acid secretion that causes heartburn in GERD patients.

CBD and ECS will prevent or reduce the severity of GERD by reducing inflammation and mucosal damage. Besides, it may help lower esophageal relaxation.

CBD for Pain Management

Pain is a common problem for GERD patients. CBD is known to activate CB1 and CB2 cannabinoid receptors to produce analgesic effects that help relieve pain, including pain from the gastrointestinal tract.

Compared to conventional pain medications, CBD oil for pain relief is a safer alternative for acid reflux patients. Many people suffering from acid reflux are aware of CBD and pain management benefits and are using CBD to derive its positive health benefits.

People with GERD experience pain in the chest, throat, or stomach. Certain pain medications can make GERD worse. They include:

This is where marijuana comes in. CBD can help reduce pain, meaning you do not have to take pain medications that can worsen GERD. Marijuana is better than medicine for acid reflux and will alleviate pain without irritating your stomach and esophagus.

Cannabis for acid reflux Relieves Stomach Acid

Although clinical trials on the effects of cannabis on stomach acid secretion are yet to be conducted, some preclinical studies suggest that cannabinoids may help inhibit gastric acid production.

In a study involving rats, cannabinoids were found to reduce stress-induced ulcers. That being the case, researchers believe that cannabis may help inhibit gastric acid secretion in humans.

Some cannabinoids are known to protect the stomach lining, meaning cannabis may be useful for GERD patients. So CBD can be one of the best acid reflux natural remedies for people chronically suffering from GERD.

Marijuana for GERD Reduces Inflammation

Is CBD good for GERD ? Although more research is required to determine if marijuana is a useful option for treating GERD, available studies suggest that cannabis may help boost endocannabinoid’s ability to reduce inflammation.

In turn, this might help combat GERD symptoms and repair mucosal damage. CBD also binds to cannabinoid receptors in the gastrointestinal system to prevent peristalsis (involuntary muscle movements), thus reducing the chances of the stomach acid going back into the esophagus.

CBD Decreases Stress

Can stress cause acid reflux ? Yes, stress and anxiety are known to trigger GERD symptoms. Luckily, medical cannabis may help you feel less anxious and overwhelmed. In the end, this might reduce stress-related ailments like stomach pain and nausea.

Your mental health is closely related to gastrointestinal health (GI). Conversely, stress and GERD are linked.

Taking medical marijuana may help calm your mind. However, talk to your doctor about the right dosage, as taking a higher THC dose can hurt you.

What’s the Best Way to Take CBD for Acid Reflux?

Having that you have read to this point, it’s likely you want to try CBD for GERD and are wondering how to take it. Here’s how to take CBD for acid reflux :

CBD Oil for Acid Reflux Benefits

To get the best benefits of CBD for acid reflux , you should know about CBD oil for GERD dosage . As the name suggests, CBD oil comes in a liquid form. Taking CBD oil for acid reflux is straightforward – measure an appropriate dose using a glass dropper and place it under the tongue.

Hold it in your mouth for about one minute before swallowing it. You will start feeling the effects of CBD oil within fifteen to thirty minutes of use and last up to six hours.

CBD Vapes – Best Medicine for Acid Reflux

If you are looking for the fastest and effective way of taking CBD for GERD , vaping is the way to go. Vaping has the highest bioavailability than tinctures and oral CBD products, as it gets into the bloodstream within three to five minutes of inhalation.

However, compared to CBD oils, CBD vape effects last for a few hours, meaning it might not be the best option if you need long-lasting effects from GERD symptoms.

CBD Capsules – For Heartburn and Acid Reflux Relief

CBD capsules may be ideal for you if you want to take CBD on the go. CBD capsules offer a discreet way to use CBD in your workplace.

However, taking CBD for acid reflux or GERD in the form of capsules will have a slower onset (between 40 and 90 minutes) than CBD oils and vapes. CBD capsules need to pass through your digestive system to feel the effect.

CBD Edibles and Acid Reflux Benefits

CBD edibles come in different flavors, making it a more enjoyable way to take CBD. However, when taking CBD gummies for GERD, keep in mind that the effects delay as they will have to pass through the liver.

How much CBD to Take for Acid Reflux?

Since the FDA does not control many CBD products, there is no standard recommendation of CBD dosage for acid reflux.

The right CBD dosage for you will depend on various factors, including:

  • Gender
  • Age
  • Weight
  • The severity of the symptoms
  • Unique body chemistry
  • Prior CBD experience

As a rule of thumb, start small (about 1 – 6 mg of CBD for every 10 pounds) and increase slowly until you get your ideal dosage. Keep a record of how each dose affects your GERD symptoms.

If taken in the right dosage, CBD is the best medicine for acid reflux and can relieve your symptoms to a great extent.

CBD for Acid Reflux Side Effects

As with any other medication, cannabis use may have side effects. Talk to your doctor about the best CBD/THC levels for you and the best method of use to reduce the risk of side effects.

Depending on the cannabis strain that you take, dose, and your CBD experience , you may experience any of the following side effects:

  • Dry mouth
  • Insomnia
  • Fatigue
  • Diarrhea
  • Red eyes
  • Paranoia
  • Drowsiness
  • Constipation
  • Dizziness
  • Impaired balance

So, Should You Take CBD for Acid Reflux ?

Although much research is needed, CBD has been shown to help with acid reflux and GERD. Marijuana interacts with the endocannabinoid system to soften the gastrointestinal muscles and protect the lining from damage.

That way, it leads to improved peristalsis, thus preventing stomach content’s backflow in the esophagus .

Talk to your doctor before taking CBD for acid reflux or GERD, especially if you take other medications.

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