Urinary bladder and the endocannabinoid system
Lining, muscle and sensory nerves.
Lining, muscle and sensory nerves. 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.
Kidneys and urinary tractCB1 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?
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.
Urinary bladder: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 is moderate across the whole bladder; CB2 RNA is very low. Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 3.4 | moderate |
| CB2 | CNR2 | 0.3 | very low |
What does it do there?
In the human bladder, both receptors have been shown both in the inner lining (urothelium) and in the muscle layer (detrusor). In one study, RNA for CB1 was higher than for CB2 in both layers; in another study that examined rat, monkey and human bladders together, however, CB2 was higher in the inner lining (mucosa) than in the muscle layer and was also found in the sensory nerves just beneath the lining. The lining of the human bladder also contains the enzyme that breaks down anandamide (FAAH), in the same place as CB2. In the laboratory, stimulating either receptor reduced electrically induced contraction in muscle strips taken from the human bladder. Human Protein AtlasHuman tissueTyagi 2009Human tissueBakali 2013Human tissueAnimalCell / labGratzke 2009Human tissueAnimalStrittmatter 2012Human tissueAnimalHedlund 2014Review
According to a review, these receptors in the bladder are found mainly in the inner lining and in nerve endings; the findings suggest that the endocannabinoid system normally keeps the bladder's sensory function continuously turned down while urine is stored and emptied. In mice, a cannabinoid stimulant given into the bladder reduced the firing of sensory nerves while the bladder was being filled; a substance that blocks CB1 abolished this effect. In mice lacking CB1, urination was more frequent and the amount of urine the bladder could hold was smaller. According to another review, it is still unclear which receptor dominates these sensory signals. Christie 2021ReviewWalczak 2009AnimalFüllhase 2014AnimalCampeau 2014AnimalHedlund 2014Review
In bladder samples from people with painful bladder syndrome and with bladder muscle overactivity of unknown cause, CB1-bearing nerve fibers beneath the lining were denser than in the comparison group; this density was related to pain and urgency scores. In people with bladder muscle overactivity, RNA for CB1 was found to be higher in the lining and lower in the muscle layer. Mukerji 2010Human tissueBakali 2016Human tissue
Student level: terms and cell types
In HPA tissue data, the urinary bladder shows CNR1 at 3.4 and CNR2 at 0.3 nTPM. In detrusor and urothelium separated by microdissection from the human bladder, CB1 and CB2 were shown by qPCR, immunohistochemistry and western blot; mRNA for both receptors in the urothelium was about twice that in the detrusor (difference not significant), and in both tissues CB1 mRNA was significantly higher than CB2; selective CB1 and CB2 agonists reduced electrically stimulated detrusor contraction. In the human bladder, CB2 was in both the urothelium and the detrusor, and in the rat only in the detrusor; CB1, TRPV1, FAAH and NAPE-PLD were present in both species. In the study that examined rat, monkey and human detrusor together, CB2 (not CB1) was higher in the mucosa than in the detrusor; in the suburothelium there were CB2-bearing nerves carrying TRPV1 or CGRP, and in the detrusor CB2-bearing fibers together with VAChT. FAAH mRNA and protein were found in human, mouse and rat mucosa; in human and rat urothelium, FAAH and CB2 were in the same place. Human Protein AtlasHuman tissueTyagi 2009Human tissueBakali 2013Human tissueAnimalCell / labGratzke 2009Human tissueAnimalStrittmatter 2012Human tissueAnimalHedlund 2014Review
According to a review, CB1 and CB2 in the bladder are found mainly in the urothelium and on the axons and terminals of motor and sensory neurons; the findings suggest that the endocannabinoid system continuously suppresses sensory bladder function during storage and voiding under normal conditions. In mice, CB1 protein was shown in the urothelium and nerve fibers, together with P2X3 in urothelial cells and some fibers; an agonist given into the bladder reduced pelvic nerve afferent activity evoked by mechanical stimulation, and AM251 abolished this effect. In CB1 knockout mice, voiding frequency and spontaneous bladder activity were higher, and bladder capacity, voided volume and compliance were lower; in wild-type mice, rimonabant produced similar urodynamic changes. In CB2 knockout mice, on the other hand, the interval between contractions, capacity and compliance were higher; the authors found this unexpected and suggested it could be explained by a change in central control of voiding. According to a review, it is unclear which receptor dominates sensory signaling or whether there is a difference between peripheral and central sites. Christie 2021ReviewWalczak 2009AnimalFüllhase 2014AnimalCampeau 2014AnimalHedlund 2014Review
In samples of painful bladder syndrome (PBS) and idiopathic detrusor overactivity (IDO), suburothelial CB1-immunoreactive nerve fibers, and in IDO also those in the detrusor, were significantly increased compared with controls; suburothelial fiber density was related to the pain score in PBS (r = 0.69) and the urgency score in IDO (r = 0.66). In detrusor overactivity, CB1 transcripts were higher in the urothelium and lower in the detrusor; CB1 was in the same place as ChAT-positive cholinergic nerves in the detrusor and as PGP9.5 in the urothelium and detrusor; CB2 was in the same place as ChAT and PGP9.5 in both layers. Mukerji 2010Human tissueBakali 2016Human tissue
Expert level: method notes and numbers
Urinary bladder: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 is moderate across the whole bladder; CB2 RNA is very low. Human Protein AtlasHuman tissue
Method note
Tissue studies. Tyagi 2009: human bladder, detrusor n = 6, urothelium n = 8; qPCR, immunohistochemistry, western blot; nerve-stimulated detrusor contraction in an organ bath. Gratzke 2009: rat, monkey and human detrusor, western blot and immunohistochemistry; the abstract does not break down the distribution findings by species; in rat cystometry, CP55,940 increased the micturition interval by 46% and the threshold pressure by 124%. Bakali 2013: human and Wistar rat bladder; CB1 protein at 57 kDa in rat and 40 kDa in human (not explained in the abstract). Bakali 2016: in normal human bladder, receptor density by [³H]-CP-55,940 binding was 421 ± 104 fmol/mg protein; sample size not in the abstract. Mukerji 2010: PBS n = 13, IDO n = 14, controls with asymptomatic microscopic hematuria n = 16 (controls were not healthy volunteers). Strittmatter 2012: human, mouse and rat bladder; the FAAH inhibitor was tested only in rats. The CB1–CB2 ratio is inconsistent between studies (CB1 > CB2 in Tyagi; CB2 stands out in the mucosa in Gratzke); the abstracts do not discuss why. Tyagi 2009Human tissueGratzke 2009Human tissueAnimalBakali 2013Human tissueAnimalCell / labBakali 2016Human tissueMukerji 2010Human tissueStrittmatter 2012Human tissueAnimal
Animal and CBD experiments. Walczak 2009: C57BL/6 mouse, ex vivo bladder–nerve preparation, AZ12646915 into the bladder. Füllhase 2014: female mice, 20 wild-type and 20 CB1 knockout; conscious cystometry (e.g., micturition interval 3.24 and 7.32 min). Campeau 2014: female CB2 knockout mice. Capasso 2011: strips from male Wistar rat and human bladder body, organ bath; in rats the extract reduced only acetylcholine contraction (not contraction by electrical stimulation, KCl or α,β-methylene ATP); the effect in rats was increased by TRPV1 blockers, while the effect in humans did not change; concentrations not in the abstract. Kuret 2023: SV-HUC1 human urothelial cells stimulated with TNFα. Peskar 2026: cyclophosphamide-induced bladder inflammation in mice, intraperitoneal CBD; dose not in the abstract. Walczak 2009AnimalFüllhase 2014AnimalCampeau 2014AnimalCapasso 2011Human tissueAnimalKuret 2023Cell / labPeskar 2026Animal
The urethra (urinary channel) was left out of the model because it differs between the sexes.
What is known about CBD?
In the laboratory, in strips cut from the human bladder wall, pure CBD and a CBD-rich cannabis extract reduced contraction caused by acetylcholine; the extract had the same effect in rat strips. In a human cell line derived from bladder lining cells, CBD reduced inflammatory messengers and oxidative stress in cells given an inflammatory stimulus; blocking the PPARγ receptor markedly weakened these effects. In mice with experimental bladder inflammation, CBD supported repair of the lining and reduced inflammation. These are tissue, cell and animal experiments. Capasso 2011Human tissueAnimalKuret 2023Cell / labPeskar 2026Animal
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 | 0.3 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 4.6 | liver (21.8) |
| GPR55 | Long an "orphan" receptor · in the cell membrane | 0.8 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 63.1 | 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 | 10.0 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 3.3 | kidney (13.9) |
| FAAH | Breaks down anandamide | 6.7 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 0.5 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 6.3 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 38.7 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 6.0 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 38.3 | epididymis (125.2) |
| Enzymes that break down CBD and THC | |||
| CYP3A4 | Breaks down CBD and THC | 0.0 | liver (3,367.1) |
| CYP2C19 | Breaks down CBD | 0.0 | liver (178.0) |
| CYP2C9 | Breaks down THC | 0.0 | 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
- Urinary bladder
- Urinary Bladder · MeSH D001743 · UBERON 0001255 · Wikidata Q9382
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Urinary bladder and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/idrar/
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 16 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
- Tyagi V, Philips BJ, Su R et al. Differential expression of functional cannabinoid receptors in human bladder detrusor and urothelium. J Urol. 2009;181(4):1932-8. PMID 19237176 · doi:10.1016/j.juro.2008.11.078 Human tissue
- Bakali E, Elliott RA, Taylor AH et al. Distribution and function of the endocannabinoid system in the rat and human bladder. Int Urogynecol J. 2013;24(5):855-63. PMID 23081739 · doi:10.1007/s00192-012-1954-1 Human tissueAnimalCell / lab
- Gratzke C, Streng T, Park A et al. Distribution and function of cannabinoid receptors 1 and 2 in the rat, monkey and human bladder. J Urol. 2009;181(4):1939-48. PMID 19237169 · doi:10.1016/j.juro.2008.11.079 Human tissueAnimal
- Strittmatter F, Gandaglia G, Benigni F et al. Expression of fatty acid amide hydrolase (FAAH) in human, mouse, and rat urinary bladder and effects of FAAH inhibition on bladder function in awake rats. Eur Urol. 2012;61(1):98-106. PMID 21930339 · doi:10.1016/j.eururo.2011.09.002 Human tissueAnimal
- Hedlund P. Cannabinoids and the endocannabinoid system in lower urinary tract function and dysfunction. Neurourol Urodyn. 2014;33(1):46-53. PMID 24285567 · doi:10.1002/nau.22442 Review
- Christie S, Brookes S, Zagorodnyuk V. Endocannabinoids in Bladder Sensory Mechanisms in Health and Diseases. Front Pharmacol. 2021;12:708989. PMID 34290614 · doi:10.3389/fphar.2021.708989 Review
- Walczak JS, Price TJ, Cervero F. Cannabinoid CB1 receptors are expressed in the mouse urinary bladder and their activation modulates afferent bladder activity. Neuroscience. 2009;159(3):1154-63. PMID 19356696 · doi:10.1016/j.neuroscience.2009.01.050 Animal
- Füllhase C, Campeau L, Sibaev A et al. Bladder function in a cannabinoid receptor type 1 knockout mouse. BJU Int. 2014;113(1):144-51. PMID 24053792 · doi:10.1111/bju.12350 Animal
- Campeau L, Füllhase C, Sawada N et al. Characterization of bladder function in a cannabinoid receptor type 2 knockout mouse in vivo and in vitro. Neurourol Urodyn. 2014;33(5):566-70. PMID 23908133 · doi:10.1002/nau.22454 Animal
- Mukerji G, Yiangou Y, Agarwal SK, Anand P. Increased cannabinoid receptor 1-immunoreactive nerve fibers in overactive and painful bladder disorders and their correlation with symptoms. Urology. 2010;75(6):1514.e15-20. PMID 20346490 · doi:10.1016/j.urology.2009.12.051 Human tissue
- Bakali E, McDonald J, Elliott RA et al. Cannabinoid receptor expression in the bladder is altered in detrusor overactivity. Int Urogynecol J. 2016;27(1):129-39. PMID 26224382 · doi:10.1007/s00192-015-2802-x Human tissue
- Capasso R, Aviello G, Borrelli F et al. Inhibitory effect of standardized cannabis sativa extract and its ingredient cannabidiol on rat and human bladder contractility. Urology. 2011;77(4):1006.e9-1006.e15. PMID 21310467 · doi:10.1016/j.urology.2010.12.006 Human tissueAnimal
- Kuret T, Kreft ME, Romih R, Veranič P. Cannabidiol as a Promising Therapeutic Option in IC/BPS: In Vitro Evaluation of Its Protective Effects against Inflammation and Oxidative Stress. Int J Mol Sci. 2023;24(5):5055. PMID 36902479 · doi:10.3390/ijms24055055 Cell / lab
- Peskar D, Kerec Kos M, Tavčar Š et al. CBD Promotes Structural and Functional Epithelial Restoration and Alleviates Inflammation in a Mouse Model of Interstitial Cystitis. Pharmaceutics. 2026;18(4):458. PMID 42076110 · doi:10.3390/pharmaceutics18040458 Animal
- 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