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Intestine and the endocannabinoid system

Movement, secretion and inflammation.

Movement, secretion and inflammation. 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 high · CB2 moderate (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?

About 1.4 MB to download.

Level
Reproductive organs

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.
CB110.0 nTPM
CB23.1 nTPM

Colon · Small intestine: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 is 10.0 in the colon and 8.1 in the small intestine; CB2 is 3.1 in the small intestine and 0.2 in the colon. Human Protein AtlasHuman tissue

Human Protein Atlas v25, tissue RNA consensus data: Colon · Small intestine
ReceptorGeneRNA (nTPM)Level
CB1CNR110high
CB2CNR23.1moderate

What does it do there?

The endocannabinoid system is found throughout the digestive tract: in the gut's nerve network, in the cells lining the gut, and in immune cells. It plays a role in regulating gut movement, secretion, appetite, nausea, gut sensitivity and inflammation. Izzo and Sharkey 2010ReviewKulkarni-Narla and Brown 2000AnimalWright 2005Human tissueCell / lab

Student level: terms and cell types

The endocannabinoid system is widespread in the digestive tract, with regional differences and organ-specific effects; its cellular targets are the enteric nervous system, the epithelium and immune cells. It is involved in regulating food intake, nausea and vomiting, gastric secretion and gastroprotection, motility, ion transport, visceral sensation, intestinal inflammation and cell proliferation. In pig ileum and colon, CB1 was found in the myenteric and submucosal plexuses, in neurons carrying the cholinergic marker ChAT. In human colon, CB1 was seen in normal epithelium, smooth muscle and the submucosal/myenteric plexus; CB1 and CB2 were seen in lamina propria plasma cells, and only CB2 in macrophages. Izzo and Sharkey 2010ReviewKulkarni-Narla and Brown 2000AnimalWright 2005Human tissueCell / lab

Expert level: method notes and numbers
CB110.0 nTPM
CB23.1 nTPM

Colon · Small intestine: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 is 10.0 in the colon and 8.1 in the small intestine; CB2 is 3.1 in the small intestine and 0.2 in the colon. Human Protein AtlasHuman tissue

Method note

Izzo and Sharkey 2010: review; besides CB1 and CB2, TRPV1, PPARα, GPR55 and GPR119 are also targets. Kulkarni-Narla and Brown 2000: immunofluorescence in pig ileum and distal colon with two antisera against the human CB1 N-terminus; CB1-positive neurons did not carry VIP or NO synthase. Wright 2005: immunohistochemistry in human colon tissue, immunoblotting and wound-healing experiments in epithelial cells. Izzo and Sharkey 2010ReviewKulkarni-Narla and Brown 2000AnimalWright 2005Human tissueCell / lab

HPA tissue consensus data: CB1 colon 10.0, small intestine 8.1, stomach 3.4, rectum 1.7, duodenum 0.6; CB2 small intestine 3.1, appendix 2.2, stomach 0.4, rectum 0.3, colon 0.2. Human Protein AtlasHuman tissue

What is known about CBD?

In a randomized, double-blind study in healthy volunteers, in a setup where the painkiller aspirin increased gut permeability, both CBD and a similar fatty acid derivative (palmitoylethanolamide) reduced the passage of sugar molecules from the gut into the blood compared with an inactive drug (placebo). In the same paper, permeability raised by inflammation went down in gut cells in the lab; in human colon tissue removed during surgery, CBD prevented the inflammation-driven drop in gene expression of a tight junction protein (claudin-5). This is not a disease study: the effect on gut permeability was not measured in people with inflammatory bowel disease.

A year of watery diarrhea and inflammation of the colon visible only under a microscope (microscopic colitis) was reported in a 75-year-old woman who used CBD oil; it cleared up when CBD was stopped and the diarrhea was treated, and it came back when CBD was restarted twice while treatment continued. This is a single case report; it does not prove cause and effect.

No effect found Weak evidence

In the guide: Crohn’s, Ulcerative Colitis and CBD

In research, CBD was not seen to help with this condition. If you are considering CBD, you can talk with your doctor or pharmacist, including about the medicines you take.

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.

Human Protein Atlas v25, tissue RNA consensus data: colon and small intestine (nTPM)
GeneWhat does it do?ColonSmall intestineTissue where it is read the most
Receptors
CB1 CNR1Cannabinoid receptor10.08.1cerebral cortex (18.6)
CB2 CNR2Cannabinoid receptor0.23.1spleen (8.4)
TRPV1Heat and chili pepper sensor · ion channel5.17.7liver (21.8)
GPR55Long an "orphan" receptor · in the cell membrane0.82.1testis (4.4)
PPARγ PPARGGene switch · in the cell nucleus47.813.4adipose tissue (153.2)
5-HT1A HTR1ASerotonin receptor · in the cell membrane0.00.0hippocampal formation (6.1)
TRPV2Relative of TRPV1 · ion channel7.010.3lung (29.5)
Endocannabinoid enzymes
NAPE-PLD NAPEPLDMakes anandamide7.29.1kidney (13.9)
FAAHBreaks down anandamide18.820.7testis (46.0)
DAGLα DAGLAMakes 2-AG2.92.2cerebral cortex (12.3)
DAGLβ DAGLBMakes 2-AG6.67.4adrenal gland (15.2)
MGL MGLLBreaks down 2-AG74.946.0adipose tissue (161.3)
ABHD6Breaks down 2-AG13.249.2liver (60.7)
ABHD12Breaks down 2-AG34.549.6epididymis (125.2)
Enzymes that break down CBD and THC
CYP3A4Breaks down CBD and THC2.9754.5liver (3,367.1)
CYP2C19Breaks down CBD0.313.3liver (178.0)
CYP2C9Breaks down THC1.343.6liver (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. This region corresponds to two HPA tissues; the light on the map shows the higher of the two. Human Protein Atlas (layers)Human tissue

Identifiers and citation

Intestine
Intestines · MeSH D007422 · UBERON 0000160 · Wikidata Q9639
Receptors
CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)

How to cite: cbd.school editorial team. Intestine and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/bagirsak/

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 5 references
  1. 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
  2. Izzo AA, Sharkey KA. Cannabinoids and the gut: new developments and emerging concepts. Pharmacol Ther. 2010;126(1):21-38. PMID 20117132 · doi:10.1016/j.pharmthera.2009.12.005 Review
  3. Kulkarni-Narla A, Brown DR. Localization of CB1-cannabinoid receptor immunoreactivity in the porcine enteric nervous system. Cell Tissue Res. 2000;302(1):73-80. PMID 11079717 · doi:10.1007/s004410000261 Animal
  4. Wright K, Rooney N, Feeney M et al. Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology. 2005;129(2):437-53. PMID 16083701 Human tissueCell / lab
  5. 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