Stomach and the endocannabinoid system
Acid, emptying and the hunger signal.
Acid, emptying and the hunger signal. Where the cannabinoid receptors CB1 and CB2 sit in this region, what they do there, and what is actually known about CBD; at three levels for Everyone, Students and Experts, with sources.
Digestion and metabolismCB1 moderate · CB2 very low (Human Protein Atlas)Last updated:
What's on this page?
Interactive 3D · real anatomy and real data
Where in your body are the cannabinoid receptors?
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Regions
How to read it Choose a region, or tap a glowing point on the map.
- Solid light is the CB1 receptor, a ring is CB2. Each region has its own color; the color only tells regions apart.
- The strength of the light is the receptor gene level measured in human tissue (Human Protein Atlas). That is why the liver’s point is dim: a healthy liver has few receptors.
- With the layer selector above you can also see other receptors, the enzymes that make and break down endocannabinoids, and the liver enzymes that break down CBD and THC.
- Every piece of information shows its source and the type of evidence (human, animal, cell). You can change the reading level above.
- Drag to rotate. Use the + and − buttons to zoom; on a computer, Ctrl or ⌘ with the scroll wheel, on a phone, two fingers.
Stomach: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 is moderate across the whole organ; in the human stomach lining it was shown in the acid-secreting cells. Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 3.4 | moderate |
| CB2 | CNR2 | 0.4 | very low |
What does it do there?
The acid-secreting cells lining the stomach carry the CB1 receptor: in human stomach biopsies with normal findings, CB1 in the stomach lining was seen only in these cells. In human tissue, RNA for CB1 and CB2 was found in the stomach, and RNA for CB1 in the vagus nerve, which links the stomach to the brain. In rats, CB1 sat on the nerves in the stomach wall; cannabinoids lowered stomach acid through these nerves and protected the stomach from stress-induced sores. Human Protein AtlasHuman tissuePazos 2008Human tissueBurdyga 2004AnimalHuman tissueAdami 2002AnimalCoruzzi 2006AnimalGermanò 2001AnimalGyires and Zádori 2016Review
In controlled studies, THC and a synthetic THC medicine (dronabinol) slowed the emptying of solid food from the stomach in healthy volunteers; a low dose of THC given into a vein, however, did not change the emptying of liquid. A drug that blocks CB1 reduced the accommodation reflex that increases stomach volume after a meal; this suggests that the body's own endocannabinoids play a role in this reflex. In ferrets, CB1 was also found in the nerve network of the stomach wall; the anti-vomiting effect of cannabinoids, however, worked through CB1 in the brainstem. McCallum 1999Human · clinical studyEsfandyari 2006Human · clinical studyBateman 1983Human · clinical studyAmeloot 2010Human · clinical studyKrowicki 1999AnimalVan Sickle 2001Animal
Ghrelin is one of the signals that regulate eating, and its main source is the stomach. In rats, blocking CB1 in the body (outside the brain) reduced ghrelin release from the stomach and reduced eating only in food-deprived animals; this effect was not seen in animals whose vagus nerve had been cut. In rats, CB1 on the nerves that carry information from the stomach and duodenum to the brain rose during fasting and fell quickly after eating. In a controlled human study with oral THC, one form of ghrelin in the blood fell before a meal, while the amount of food taken by mouth increased. Senin 2013AnimalBurdyga 2004AnimalHuman tissueWeltens 2019Human · clinical study
Student level: terms and cell types
In HPA tissue data, the stomach shows CNR1 at 3.4 and CNR2 at 0.4 nTPM. In human gastric mucosa, CB1 was shown in the acid-secreting parietal cells that carry H⁺/K⁺-ATPase (western blot, RT-PCR, in situ hybridization, immunohistochemistry, double immunofluorescence); there was no overlap with endocrine cell markers (chromogranin A, synaptophysin). CB1 protein was markedly higher in the parietal-cell-rich body (corpus) mucosa than in the antrum, where parietal cells are almost absent. In the human vagus nerve trunk and gastric corpus, RT-PCR detected CB1, and CB2 only in the stomach; in human vagus samples, CB1 immunoreactivity was seen in the cell bodies of a population of neurons. In the rat stomach, CB1 was in the same nerve elements as the cholinergic marker ChAT in the fundus, corpus and antrum, and CB2 was not seen; CB1 agonists reduced acid secretion stimulated by pentagastrin and 2-deoxy-D-glucose but did not change histamine-stimulated secretion. In the isolated rat fundus, cannabinoids did not affect acid; the authors concluded that CB1 lies not on the parietal cell but on the vagal pathways to the stomach. The human parietal-cell finding diverges from this rat finding. In rats, CB1 stimulation reduced gastric ulcers caused by cold and restraint stress; according to a review of the experimental findings, CB1 stimulation reduces gastric acid and gastric motility, and reduces mucosal damage caused by stress, NSAIDs and alcohol through partly peripheral and partly central pathways. Human Protein AtlasHuman tissuePazos 2008Human tissueBurdyga 2004AnimalHuman tissueAdami 2002AnimalCoruzzi 2006AnimalGermanò 2001AnimalGyires and Zádori 2016Review
In a randomized double-blind study (13 healthy volunteers), THC slowed solid-meal emptying compared with placebo in every participant; 120 minutes after the meal, markedly more labeled food remained in the stomach than with placebo, and the delay was not related to the blood THC level. In a randomized placebo-controlled study (30 healthy volunteers), dronabinol delayed overall gastric emptying measured by scintigraphy; the effect was more marked in women, and gastric volumes and small- and large-bowel transit did not change. Intravenous THC did not change liquid emptying (7 volunteers). The CB1 antagonist rimonabant reduced meal-induced gastric accommodation measured with a barostat; it did not change gastric compliance or sensitivity to distension. In rats, intravenous THC reduced intragastric pressure and pyloric contractions; this effect was abolished by vagotomy and ganglion blockade and fully blocked by a CB1 antagonist. In ferrets, CB1 and FAAH were found in the dorsal vagal complex of the brainstem, and CB1 also in the myenteric plexus of the stomach and duodenum; CB1 agonists reduced vomiting, and the antagonist alone had no effect but increased the response to an emetic stimulus. McCallum 1999Human · clinical studyEsfandyari 2006Human · clinical studyBateman 1983Human · clinical studyAmeloot 2010Human · clinical studyKrowicki 1999AnimalVan Sickle 2001Animal
The stomach is the main source of ghrelin. In rats, peripheral CB1 blockade (rimonabant) reduced food intake only in fasted animals; the authors attributed this to lower ghrelin secretion caused by activation of the mTOR/S6K1 pathway in the stomach; chronic rapamycin abolished rimonabant's ghrelin effect, and surgical vagotomy abolished the food intake effect. In rats, vagal afferent neurons carrying the CCK-1 receptor and projecting to the stomach and duodenum also carried CB1; fasting for 12 hours or longer increased CB1 in the nodose ganglion, and refeeding quickly reduced it; this drop was blocked by a CCK-1 antagonist and mimicked by giving CCK to fasted rats. In a single-blind, placebo-controlled 2×2 crossover study (17 healthy people), oral THC raised plasma motilin and lowered octanoylated ghrelin before a milkshake and suppressed the GLP-1 response to the shake; oral intake of the shake increased, while intake by direct infusion into the stomach did not change. Senin 2013AnimalBurdyga 2004AnimalHuman tissueWeltens 2019Human · clinical study
Expert level: method notes and numbers
Stomach: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 is moderate across the whole organ; in the human stomach lining it was shown in the acid-secreting cells. Human Protein AtlasHuman tissue
Method note
Location and acid. Pazos 2008: 20 dyspeptic patients referred for endoscopy (8 men, 12 women) were invited; two antrum and two corpus biopsies were taken from each; only samples with normal endoscopy and histology and negative for H. pylori were used (the number included is not in the text; the abstract says "healthy individuals"). Western blot showed a single band at ≈60 kDa that disappeared with the immunizing peptide; on RT-PCR, CB1 mRNA in gastric epithelium was lower than in human cerebellum. Burdyga 2004: human vagal trunks from gastroesophageal cancer resections; RT-PCR detected CB1 in the vagus and gastric corpus, and CB2 only in the stomach. Adami 2002: anesthetized rat, lumen perfusion; the agonist effect was prevented by the CB1 antagonist SR141716A and not by the CB2 antagonist SR144528; bilateral cervical vagotomy and hexamethonium reduced but did not abolish the peak effect, and atropine did not change it. Coruzzi 2006: in the isolated fundus (immature rat), agonists and antagonists had no effect; in vivo, HU-210 was effective at all ages. Germanò 2001: cold/restraint stress; WIN 55,212-2 was effective, but not its inactive isomer WIN 55,212-3; the effect was abolished by SR141716A but not by SR144528. Pazos 2008Human tissueBurdyga 2004AnimalHuman tissueAdami 2002AnimalCoruzzi 2006AnimalGermanò 2001Animal
Gastric motility and vomiting. McCallum 1999: THC (10 mg/m² body surface area) or placebo on two separate days; technetium-labeled solid meal; at minute 120, retention was 45.6% ± 7.2 (placebo) and 73.9% ± 7.1 (THC), P < 0.001; the route of administration is not in the abstract; the authors wrote that the antiemetic effect may be mediated by the central nervous system. Esfandyari 2006: 30 healthy volunteers, dronabinol 5 mg twice daily (three doses) or placebo; gastric emptying overall P = 0.018 (women 0.011, men 0.184); in men, fasting gastric volume was larger with dronabinol (238 ± 17 vs. 185 ± 16; P = 0.04; units not given in the abstract). Bateman 1983: 7 volunteers, intravenous THC 0.5 and 1 mg; pulse and psychological measures changed. Ameloot 2010: 12 healthy volunteers, rimonabant 20 mg/day or placebo for 4 days, double-blind crossover; accommodation 154.3 ± 30.9 vs. 64.3 ± 32.4 mL (P = 0.02); maximum nutrient tolerance and meal-related symptoms did not change. Krowicki 1999: anesthetized rat; applying THC to the surface of the dorsal medulla produced small, brief effects. Van Sickle 2001: ferret; the CB1 agonists THC, WIN 55,212-2 and methanandamide. McCallum 1999Human · clinical studyEsfandyari 2006Human · clinical studyBateman 1983Human · clinical studyAmeloot 2010Human · clinical studyKrowicki 1999AnimalVan Sickle 2001Animal
Ghrelin and the appetite signal. Senin 2013: rat, in vivo and in vitro. Burdyga 2004: rat nodose ganglion, retrograde tracing from the stomach and duodenum; CB1 by RT-PCR, immunohistochemistry and in situ hybridization. Weltens 2019: 17 healthy people, single-blind; motilin P = 0.0021, octanoyl-ghrelin P = 0.023, oral shake intake P = 0.0005. Senin 2013AnimalBurdyga 2004AnimalHuman tissueWeltens 2019Human · clinical study
What is known about CBD?
Gastric measurements were taken in two controlled studies in which the approved CBD medicine was given for four weeks. In patients with indigestion without delayed gastric emptying (functional dyspepsia), there was no significant difference between CBD and placebo in gastric emptying, gastric volumes or a satiation test. In patients with delayed gastric emptying (gastroparesis), however, solid food emptied from the stomach more slowly in those taking CBD than in the placebo group; the difference in the study's main emptying measure was not significant. In a small study of 15 healthy adults, a single dose of CBD lowered blood ghrelin compared with placebo; more was eaten at lunch, and subjective appetite measures did not change. Atieh 2022Human · clinical studyZheng 2023Human · clinical studyJohnson 2026Human · clinical study
The US prescribing information for the approved CBD medicine lists digestive side effects seen more often than with placebo in controlled studies, including decreased appetite, diarrhea, weight loss, inflammation of the stomach and intestines (gastroenteritis) and abdominal pain or discomfort; in the study in patients with tuberous sclerosis complex, vomiting was also among the most common side effects. These data come from the studies in which the medicine was tested in patients with Lennox–Gastaut syndrome, Dravet syndrome and tuberous sclerosis complex. Epidiolex label (FDA)Official drug label
Not studied enough Insufficient evidence
In the guide: Chemotherapy Nausea and CBD
There is not enough research in humans. It is not known whether CBD works. CBD can interact with some cancer medicines; if you are considering it, you can talk with your oncologist and pharmacist first.
No effect found Insufficient evidence
In the guide: Appetite Loss in Cancer and CBD
Research has not found that CBD helps with this condition. CBD can interact with some cancer medicines; if you are considering it, you can talk with your oncologist and pharmacist first.
Mixed results Weak evidence
In the guide: Irritable Bowel, Stomach Problems and CBD
Research results are mixed: in gastroparesis, CBD reduced symptoms in a single small study; in indigestion and irritable bowel syndrome, no difference was seen. If you are considering CBD, you can talk with your doctor or pharmacist, including about the medicines you take.
Which receptor and enzyme genes are read in this region?
Values in this region for the genes in the map's layer selector: besides CB1 and CB2, the other targets of cannabinoids, the enzymes that make and break down endocannabinoids, and the liver enzymes that break down CBD and THC.
| Gene | What does it do? | Here | Tissue where it is read the most |
|---|---|---|---|
| Receptors | |||
| CB1 CNR1 | Cannabinoid receptor | 3.4 | cerebral cortex (18.6) |
| CB2 CNR2 | Cannabinoid receptor | 0.4 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 5.2 | liver (21.8) |
| GPR55 | Long an "orphan" receptor · in the cell membrane | 0.7 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 33.1 | adipose tissue (153.2) |
| 5-HT1A HTR1A | Serotonin receptor · in the cell membrane | 0.0 | hippocampal formation (6.1) |
| TRPV2 | Relative of TRPV1 · ion channel | 5.8 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 9.3 | kidney (13.9) |
| FAAH | Breaks down anandamide | 16.7 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 1.4 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 7.0 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 34.5 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 12.2 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 51.5 | epididymis (125.2) |
| Enzymes that break down CBD and THC | |||
| CYP3A4 | Breaks down CBD and THC | 1.1 | liver (3,367.1) |
| CYP2C19 | Breaks down CBD | 2.8 | liver (178.0) |
| CYP2C9 | Breaks down THC | 15.8 | liver (1,607.6) |
RNA level shows how much the gene is read in this tissue; it does not directly show the amount of protein or how active an enzyme is. Human Protein Atlas (layers)Human tissue
Identifiers and citation
- Stomach
- Stomach · MeSH D013270 · UBERON 0000945 · Wikidata Q1029907
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Stomach and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/mide/
The body model is derived from BodyParts3D (DBCLS, CC BY 4.0) and Z-Anatomy (CC BY-SA 4.0); receptor levels from Human Protein Atlas v25 (CC BY 4.0). The map, text and downloaded images are CC BY-SA 4.0. An independent expert review has not been done yet. All licenses
Other pages of the map
Overview: what the endocannabinoid system is, the feedback brake at the synapse, CBD's targets, lesson mode, data and licenses.
Sources
Show 20 references
- Human Protein Atlas v25: tissue RNA consensus data (rna_tissue_consensus.tsv, HPA and GTEx, nTPM) and brain region data (rna_brain_region_hpa.tsv, nTPM), CNR1 (ENSG00000118432) and CNR2 (ENSG00000188822); v25.proteinatlas.org, file date November 6, 2025, downloaded October 24, 2026. Uhlén M et al. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419. License CC BY 4.0. PMID 25613900 · doi:10.1126/science.1260419 Human tissue
- Pazos MR, Tolón RM, Benito C et al. Cannabinoid CB1 receptors are expressed by parietal cells of the human gastric mucosa. J Histochem Cytochem. 2008;56(5):511-6. PMID 18285348 · doi:10.1369/jhc.2008.950741 Human tissue
- Burdyga G, Lal S, Varro A et al. Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin. J Neurosci. 2004;24(11):2708-15. PMID 15028763 · doi:10.1523/JNEUROSCI.5404-03.2004 AnimalHuman tissue
- Adami M, Frati P, Bertini S et al. Gastric antisecretory role and immunohistochemical localization of cannabinoid receptors in the rat stomach. Br J Pharmacol. 2002;135(7):1598-606. PMID 11934799 · doi:10.1038/sj.bjp.0704625 Animal
- Coruzzi G, Adami M, Guaita E et al. Effects of cannabinoid receptor agonists on rat gastric acid secretion: discrepancy between in vitro and in vivo data. Dig Dis Sci. 2006;51(2):310-7. PMID 16534674 · doi:10.1007/s10620-006-3130-2 Animal
- Germanò MP, D'Angelo V, Mondello MR et al. Cannabinoid CB1-mediated inhibition of stress-induced gastric ulcers in rats. Naunyn Schmiedebergs Arch Pharmacol. 2001;363(2):241-4. PMID 11218077 · doi:10.1007/s002100000360 Animal
- Gyires K, Zádori ZS. Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation. Curr Neuropharmacol. 2016;14(8):935-951. PMID 26935536 · doi:10.2174/1570159x14666160303110150 Review
- McCallum RW, Soykan I, Sridhar KR et al. Delta-9-tetrahydrocannabinol delays the gastric emptying of solid food in humans: a double-blind, randomized study. Aliment Pharmacol Ther. 1999;13(1):77-80. PMID 9892882 · doi:10.1046/j.1365-2036.1999.00441.x Human · clinical study
- Esfandyari T, Camilleri M, Ferber I et al. Effect of a cannabinoid agonist on gastrointestinal transit and postprandial satiation in healthy human subjects: a randomized, placebo-controlled study. Neurogastroenterol Motil. 2006;18(9):831-8. PMID 16918762 · doi:10.1111/j.1365-2982.2006.00834.x Human · clinical study
- Bateman DN. Delta-9-tetrahydrocannabinol and gastric emptying. Br J Clin Pharmacol. 1983;15(6):749-51. PMID 6307330 · doi:10.1111/j.1365-2125.1983.tb01561.x Human · clinical study
- Ameloot K, Janssen P, Scarpellini E et al. Endocannabinoid control of gastric sensorimotor function in man. Aliment Pharmacol Ther. 2010;31(10):1123-31. PMID 20146701 · doi:10.1111/j.1365-2036.2010.04259.x Human · clinical study
- Krowicki ZK, Moerschbaecher JM, Winsauer PJ, Digavalli SV, Hornby PJ. Delta9-tetrahydrocannabinol inhibits gastric motility in the rat through cannabinoid CB1 receptors. Eur J Pharmacol. 1999;371(2-3):187-96. PMID 10357256 · doi:10.1016/s0014-2999(99)00165-x Animal
- Van Sickle MD, Oland LD, Ho W et al. Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret. Gastroenterology. 2001;121(4):767-74. PMID 11606489 · doi:10.1053/gast.2001.28466 Animal
- Senin LL, Al-Massadi O, Folgueira C et al. The gastric CB1 receptor modulates ghrelin production through the mTOR pathway to regulate food intake. PLoS One. 2013;8(11):e80339. PMID 24303008 · doi:10.1371/journal.pone.0080339 Animal
- Weltens N, Depoortere I, Tack J, Van Oudenhove L. Effect of acute Δ9-tetrahydrocannabinol administration on subjective and metabolic hormone responses to food stimuli and food intake in healthy humans: a randomized, placebo-controlled study. Am J Clin Nutr. 2019;109(4):1051-1063. PMID 30949710 · doi:10.1093/ajcn/nqz007 Human · clinical study
- Atieh J, Maselli D, Breen-Lyles M et al. Cannabidiol for Functional Dyspepsia With Normal Gastric Emptying: A Randomized Controlled Trial. Am J Gastroenterol. 2022;117(8):1296-1304. PMID 35537858 · doi:10.14309/ajg.0000000000001805 Human · clinical study
- Zheng T, BouSaba J, Taylor A et al. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023;21(13):3405-3414.e4. PMID 37482172 · doi:10.1016/j.cgh.2023.07.008 Human · clinical study
- Johnson DA, Funnell MP, Cable TG et al. A single dose of cannabidiol increases ad libitum energy intake in healthy adults but does not affect postprandial glucose or lipid metabolism. Appetite. 2026;222:108531. PMID 41825697 · doi:10.1016/j.appet.2026.108531 Human · clinical study
- EPIDIOLEX (cannabidiol) oral solution, US prescribing information (Jazz Pharmaceuticals), DailyMed setid 8bf27097-4870-43fb-94f0-f3d0871d1eec, SPL version 35 (effective May 29, 2026; on DailyMed June 15, 2026): sections 1, 2.1–2.6, 4, 5.1–5.5, 6.1, 7, 8.1, 8.2, 8.4, 8.5, 8.6, 9.2, 9.3, 11, 12.1, 12.2, 12.3, 13.1, 14.1–14.3, 17. Source Official drug label
- Human Protein Atlas v25: tissue RNA consensus data (rna_tissue_consensus.tsv, HPA and GTEx, nTPM), the 17 genes in the map's layer selector: CNR1, CNR2, TRPV1, GPR55, PPARG, HTR1A, TRPV2, NAPEPLD, FAAH, DAGLA, DAGLB, MGLL, ABHD6, ABHD12, CYP3A4, CYP2C19, CYP2C9; v25.proteinatlas.org/download/tsv/rna_tissue_consensus.tsv.zip, downloaded October 24, 2026. Uhlén M et al. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419. License CC BY 4.0. PMID 25613900 · doi:10.1126/science.1260419 Human tissue