Liver and the endocannabinoid system
Fat metabolism; a receptor that rises in disease.
Fat metabolism; a receptor that rises in disease. 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 very low · 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?
About 1.4 MB to download.
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.
Liver: RNA level of the receptor gene in human tissue (tissue consensus data). In healthy liver tissue, RNA for both receptors is very low. Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 0.1 | very low |
| CB2 | CNR2 | 0.1 | very low |
What does it do there?
The healthy liver has few receptors, but they come to the fore in disease: CB1 rose markedly in samples of cirrhosis and in the liver cells that make scar tissue. In mice, CB1 in the liver increased fat production and contributed to weight gain on a high-fat diet. Teixeira-Clerc 2006Human tissueAnimalOsei-Hyiaman 2005Animal
According to reviews, CB1 promotes fatty liver and the progression of fibrosis, while CB2 works in the direction of reducing inflammation and fibrosis. Mallat 2013Review
Student level: terms and cell types
CB1 was markedly induced in human cirrhosis samples and in the fibrogenic cells of the liver. The CB1 antagonist SR141716A reduced the wound-healing response in acute injury and prevented the progression of fibrosis in three chronic injury models; similar changes were seen in Cnr1−/− mice (a drop in TGF-β1, apoptosis of hepatic myofibroblasts). In mice, CB1 activation increased gene expression of SREBP-1c and of acetyl-CoA carboxylase-1 and fatty acid synthase; a high-fat diet increased hepatic anandamide, CB1 density and de novo fatty acid synthesis, and this synthesis fell with CB1 blockade. Teixeira-Clerc 2006Human tissueAnimalOsei-Hyiaman 2005Animal
According to a review, CB1 antagonists are an important target because of their effects on lipid metabolism and their antifibrotic properties; peripherally acting CB1 antagonists with limited brain penetration were effective in preclinical models of fatty liver. The brain-penetrant CB1 antagonist rimonabant was withdrawn from the market because of mood side effects. CB2 is considered a promising anti-inflammatory and antifibrotic target; clinical development of CB2 agonists is awaited. Mallat 2013Review
Expert level: method notes and numbers
Liver: RNA level of the receptor gene in human tissue (tissue consensus data). In healthy liver tissue, RNA for both receptors is very low. Human Protein AtlasHuman tissue
Method note
Teixeira-Clerc 2006: human cirrhotic liver samples and fibrogenic cells; three chronic liver injury models in mice; pharmacological (SR141716A) and genetic (Cnr1−/−) inactivation. Osei-Hyiaman 2005: CB1 agonist and blockade in mice, isolated hepatocytes, high-fat diet; CB1−/− mice did not gain weight on the diet despite similar calorie intake. The abstracts give no quantitative receptor density in the human liver. Teixeira-Clerc 2006Human tissueAnimalOsei-Hyiaman 2005Animal
What is known about CBD?
CBD is broken down largely in the liver by the enzymes CYP3A4 and CYP2C19; for this reason it can interact with drugs broken down by the same pathway. The approved CBD medicine can raise liver enzymes (transaminases); the risk increases with use together with valproate and at high doses. Epidiolex label (FDA)Official drug label
No effect found Insufficient evidence
In the guide: Diabetes and CBD
Research has not shown that CBD helps with this. If you are considering CBD, you can talk with your doctor or pharmacist, including about the medicines you take.
Check drug interactions · Safety
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 | 0.1 | cerebral cortex (18.6) |
| CB2 CNR2 | Cannabinoid receptor | 0.1 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 21.8 | liver (21.8) |
| GPR55 | Long an "orphan" receptor · in the cell membrane | 0.1 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 16.2 | 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 | 3.8 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 7.0 | kidney (13.9) |
| FAAH | Breaks down anandamide | 32.9 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 0.2 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 7.9 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 102.6 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 60.7 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 27.4 | epididymis (125.2) |
| Enzymes that break down CBD and THC | |||
| CYP3A4 | Breaks down CBD and THC | 3,367.1 | liver (3,367.1) |
| CYP2C19 | Breaks down CBD | 178.0 | liver (178.0) |
| CYP2C9 | Breaks down THC | 1,607.6 | 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
- Liver
- Liver · MeSH D008099 · UBERON 0002107 · Wikidata Q9368
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Liver and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/karaciger/
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 6 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
- Teixeira-Clerc F, Julien B, Grenard P et al. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med. 2006;12(6):671-6. PMID 16715087 · doi:10.1038/nm1421 Human tissueAnimal
- Osei-Hyiaman D, DePetrillo M, Pacher P et al. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest. 2005;115(5):1298-305. PMID 15864349 · doi:10.1172/JCI23057 Animal
- Mallat A, Teixeira-Clerc F, Lotersztajn S. Cannabinoid signaling and liver therapeutics. J Hepatol. 2013;59(4):891-6. PMID 23567085 · doi:10.1016/j.jhep.2013.03.032 Review
- 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