Prostate and seminal vesicles: the endocannabinoid system
Two organs that add fluid to semen.
Two organs that add fluid to semen. 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.
Reproductive organsCB1 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?
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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.
Prostate: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 RNA is low across the whole prostate, and CB2 RNA is very low; in the seminal vesicle, CB1 is 1.4 nTPM. Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 2.2 | low |
| CB2 | CNR2 | 0.1 | very low |
What does it do there?
Across the prostate as a whole, RNA for CB1 is measured at a low level and for CB2 at a very low level. The prostate is a walnut-sized gland that adds fluid to semen. In human prostate tissue, both the RNA and the protein of the CB1 receptor were found; the amount of protein was comparable to the receptor in the cerebellum, and the receptor was seen mainly in the secreting inner lining of the gland, the epithelium. Another study found CB1 in both epithelial cells and smooth muscle cells, while TRPV1, another target of cannabinoids, was only in mucosal cells. A third study showed CB1 and CB2 in the nerve fibers entering the gland: they were present in fibers carrying nitric oxide, acetylcholine or CGRP, and absent from fibers carrying adrenaline. Human Protein AtlasHuman tissueRuiz-Llorente 2003Human tissueCzifra 2009Human tissueGratzke 2010Human tissue
The tissue has not only receptors but also the enzyme that breaks down endocannabinoids. FAAH, the enzyme that breaks down anandamide, was seen in epithelial cells and blood vessel walls in prostate tissue; it was not seen in the supporting tissue in between (stroma). In a separate staining done with ready-made tissue arrays, FAAH was detected in most prostate cancer samples and was almost absent in healthy prostate samples. TRPV1 was also shown to be present in human prostate tissue and to function in prostate cells: in the laboratory, when cells were given capsaicin or a stable analog of anandamide, intracellular calcium rose, and a substance that blocks TRPV1 reversed this rise. Thors 2010Human tissueCell / labEndsley 2008Human tissueCell / labSánchez 2005Human tissueCell / lab
When the prostate contracts, it empties its secretion into the duct; nerves inside the gland start this contraction. In the laboratory, in tissue pieces prepared from the human prostate, a substance that stimulates both receptors together reduced the contraction caused by nerve stimulation. In rats there is a finding in the same direction and in more detail: there, CB1 was found not in the smooth muscle layer but in the secreting lining cells of the gland; a cannabinoid stimulant reduced electrically induced contraction in a concentration-dependent way, two substances that block CB1 reversed this effect, and a substance that blocks CB2 did not. The effect went through the cyclooxygenase pathway, not through nitric oxide. In other words, the reduction in contraction may start from the tissue's own inner lining. According to a review, these basic research findings in reproductive tissues have not yet been supported by studies in patients. Gratzke 2010Human tissueTokanovic 2007AnimalÜckert 2025Review
The amounts of these molecules change in prostate diseases. In tissue with benign prostate enlargement, CB1 was measured as markedly high, while TRPV1 did not change. In prostate cancer tissue, CB1 and TRPV1 rose together; the increase in TRPV1 rose with the grade of the tumor, while no such pattern was seen for CB1. In analyses that scored tissue from hundreds of patients one by one, high CB1 and high FAAH in the tumor epithelium were associated with disease severity at diagnosis; CB1 staining was mostly in the epithelial cell membrane and sparse in the stroma. These are tissue measurements: they do not show whether a substance is good for the disease. Czifra 2009Human tissueChung 2009Human tissueThors 2010Human tissueCell / labCipriano 2013Human tissue
Most of the seminal fluid is made by the seminal vesicles, two small sacs behind the prostate. In a study with human tissue, the genes for the CB1 and CB2 receptors, for GPR55, another target of cannabinoids, and for two forms of the enzyme that breaks down anandamide (FAAH1, FAAH2) were found to be read in these sacs. On staining, CB1, CB2 and GPR55 were dense in the secretory epithelium lining the inside of the sac and in the winding nerve fibers that reach it; the two forms of FAAH were seen inside the cuboidal cells in all layers of the epithelium. Based on this location, the researchers say the system may be related to the upkeep of the lining, to secretory function or to nerve signals that sense stretch; this is a possibility, not a measured function. A more recent review also writes that these findings in reproductive tissues have not yet been supported by studies addressing clinical conditions. Human Protein AtlasHuman tissueÜckert 2018Human tissueÜckert 2025Review
Student level: terms and cell types
In HPA tissue data, the prostate shows CNR1 at 2.2 and CNR2 at 0.1, and the seminal vesicle CNR1 at 1.4 and CNR2 at 0 nTPM. RT-PCR, western blot and immunohistochemistry showed CB1 mRNA and protein in human prostate tissue; on western blot, the protein was 58 kDa in size and its amount was comparable to the receptor in the cerebellum. On immunohistochemistry, CB1 was mainly in the epithelium, and the receptor suppressed adenylyl cyclase through a pertussis-toxin-sensitive G protein (Gi/o coupling). In a series comparing healthy, benign enlarged and cancerous prostate tissue, CB1 was detected in epithelial and smooth muscle cell types and TRPV1 only in mucosal cells (immunohistochemistry, western blot, Q-PCR). In radical prostatectomy samples, western blot gave the expected bands for CB1, CB2 and TRPA1; CB1 and CB2 immunoreactivity was on NOS-, VAChT- or CGRP-positive nerves and absent from adrenergic nerves. In nodular hyperplasia, nerves carrying these markers were sparse or absent. Human Protein AtlasHuman tissueRuiz-Llorente 2003Human tissueCzifra 2009Human tissueGratzke 2010Human tissue
In a tissue array, FAAH immunoreactivity was in tumor and non-tumor epithelial cells and in blood vessel walls, and absent from the stroma. In commercial tissue arrays, FAAH staining was seen in 109 of 157 prostate adenocarcinoma sections and in 1 of 8 healthy prostate sections (weak); in the same study, overexpressing FAAH in PC-3 cells increased 2-AG breakdown and cell migration, and reducing it with siRNA in LNCaP cells lowered breakdown and invasion. TRPV1 mRNA and protein were shown in the PC-3 and LNCaP prostate epithelial cell lines and in human prostate tissue; [125I]-resiniferatoxin binding kinetics matched TRPV1 in other tissues; capsaicin, (R)-methanandamide and resiniferatoxin increased intracellular calcium in a dose-dependent way, and capsazepine reversed this. No study was found measuring where NAPE-PLD and MAGL are located in human prostate **tissue**; the available data for these two enzymes are at the level of cell lines and rats. Thors 2010Human tissueCell / labEndsley 2008Human tissueCell / labSánchez 2005Human tissueCell / lab
In human prostate preparations, the CB1/CB2 agonist CP 55940 reduced nerve-stimulated contraction; because the abstract gives this reduction in a single sentence listing five substances together, the percentages cannot be matched to the substances (explained at the Expert level). In rat prostate, immunohistochemistry was positive for CB1 and negative for CB2; double labeling showed that CB1 was not found together with α-actin in the smooth muscle layer and was concentrated in the epithelial lining of the acini. WIN 55,212-2 suppressed contractions induced by electrical field stimulation in a concentration-dependent way; SR141716 and LY 320135 (CB1) reversed the suppression, and SR144528 (CB2) did not; indomethacin (a cyclooxygenase inhibitor) reversed it, and L-NAME (an NO synthase inhibitor) did not; PGE2 produced a similar suppression. Gratzke 2010Human tissueTokanovic 2007AnimalÜckert 2025Review
In BPH tissue, CB1 was markedly high and TRPV1 unchanged; in prostate carcinoma, CB1 and TRPV1 rose significantly at both protein and mRNA level, and the TRPV1 increase, but not the CB1 increase, was related to tumor grade. In a tissue array built from a series of transurethral resections done for urinary symptoms, CB1 immunoreactivity (CB1IR) was scored in 399 cases: it was in the epithelial cell membrane, with sparse staining in the stroma; a score at or above the median (2) was significantly associated with the rate of Gleason 8–10, metastasis at diagnosis, tumor size and cell proliferation rate. In the same array, FAAH immunoreactivity was measured in 412 patients; FAAH in the tumor epithelium was associated with disease severity and outcome at moderate CB1IR scores but not at high CB1IR scores. A third analysis found a strong association between CB1IR and phosphorylated Akt immunoreactivity; cases with both markers high had more severe disease at diagnosis. Czifra 2009Human tissueChung 2009Human tissueThors 2010Human tissueCell / labCipriano 2013Human tissue
In human seminal vesicle samples, RT-PCR gave products for CB1 (66 bp), CB2 (141 bp), GPR55 (112 bp), FAAH1 (260 bp) and FAAH2 (387 bp). On immunohistochemistry and immunofluorescence, CB1, CB2 and GPR55 were dense in the pseudostratified columnar epithelium and in varicose nerves carrying VIP and CGRP; FAAH1 and FAAH2 staining was in the cytosol of cuboidal cells in all layers of the epithelium. The abstract then also says that no immunoreactivity was detected in smooth muscle and nerve fibers; the two sentences appear to contradict each other. The study has no organ bath, secretion measurement or other functional experiment; its concluding sentence is worded as a possibility. The authors state that knowledge about the expression of the endocannabinoid system in human male reproductive tissues is scarce, which is why they did the study. Human Protein AtlasHuman tissueÜckert 2018Human tissueÜckert 2025Review
Expert level: method notes and numbers
Prostate: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 RNA is low across the whole prostate, and CB2 RNA is very low; in the seminal vesicle, CB1 is 1.4 nTPM. Human Protein AtlasHuman tissue
Method note
Location studies. Ruiz-Llorente 2003: human prostate tissue; RT-PCR, western blot (58 kDa) and immunohistochemistry, adenylyl cyclase activity by cAMP measurement; sample size not in the abstract. Czifra 2009: healthy, BPH and carcinoma tissues; immunohistochemistry, western blot, Q-PCR; sample sizes and quantitative fold increases not in the abstract. Gratzke 2010: samples from 12 patients who had radical prostatectomy; expression experiments in 6 samples, organ bath experiments in 6 samples for each substance. Which cell carries CB2 in the prostate cannot be determined from the abstracts: Czifra did not measure CB2 at all, Gratzke found it on nerve fibers, and in rat prostate CB2 could not be found. Ruiz-Llorente 2003Human tissueCzifra 2009Human tissueGratzke 2010Human tissue
Enzymes and TRPV1. For FAAH there are two independent tissue series (one the transurethral resection array in Sweden, the other commercial tissue arrays); both report staining in the epithelium and none in the stroma. Sánchez 2005's TRPV1 functional experiments were in cell lines (PC-3, LNCaP); tissue was examined only at the expression level. For MAGL, the available data are in human prostate cancer cell lines: MAGL was found to be higher in androgen-independent lines than in androgen-dependent lines. For NAPE-PLD, the available data are at the mRNA level in an orthotopic prostate tumor model in rats. Neither shows location in human prostate tissue. Thors 2010Human tissueCell / labEndsley 2008Human tissueCell / labSánchez 2005Human tissueCell / labNomura 2011Cell / labAlhouayek 2020AnimalCell / lab
Functional experiments. Gratzke 2010's functional sentence lists five substances (CP 55940, NaHS, allyl isothiocyanate, capsaicin, cinnamaldehyde) and gives four percentages; because the abstract does not show which percentage belongs to which substance, no figure was given for CP 55940 in the region text; this assessment rests only on the published abstract. Tokanovic 2007: Sprague-Dawley rat, isolated organ bath, electrical field stimulation; WIN 55,212-2 and the antagonists are given with concentration ranges in the abstract. The rat finding does not generalize to humans: in human tissue, CB1 was shown in both the epithelium and the smooth muscle, and in rats only in the epithelium. Gratzke 2010Human tissueTokanovic 2007Animal
Disease tissue series. Chung 2009: CB1IR scored in 399 cases; outcome analysis only in 269 cases receiving palliative treatment at the end stage; area under the ROC curve 0.67 (95% confidence limits 0.59–0.74); in Cox analysis, CB1IR and Gleason score were independent predictors. Thors 2010: 412 patients from the same tissue array, outcome analysis in 281 cases. Cipriano 2013: the same array, CB1IR rescored together with pAkt immunoreactivity. Because these three analyses come **from the same tissue array**, they do not count as independent confirmation; so the region text refers to them not as three separate studies but as analyses of the same tissue array. Czifra 2009 is an independent and smaller series. None of them is a treatment study. Chung 2009Human tissueThors 2010Human tissueCell / labCipriano 2013Human tissue
Single tissue study. Human seminal vesicle samples; expression of five targets by RT-PCR, location by immunohistochemistry/immunofluorescence. Sample size, which surgery the samples came from, antibody validation and negative controls are not in the abstract; there are no quantitative values, only PCR product lengths. The abstract contains a typo ("Immumohistochemistry"). The specificity of GPR55 antibodies is debated in the literature and this abstract does not address the issue; for this reason, the region text says "shown" for GPR55 and makes no claim of function. Ückert 2018Human tissue
Context and indirect data. Ückert 2025 is a review by the same group (the last author of the 2018 study is the second author of this review); it is not independent confirmation. As indirect human data, a review reports that anandamide and two similar fat molecules (PEA, OEA) were measured in human seminal fluid by liquid chromatography–mass spectrometry, and writes that in mammals, receptors or anandamide are found in reproductive organs such as the prostate. Because this fluid is a mixture of secretions from the prostate, seminal vesicles and epididymis, it is not organ-specific; for this reason it was not included in the region text. Ückert 2025ReviewSchuel 2002Human tissueReview
Visible in the male layer. The two small sacs at the upper back side of the prostate are the seminal vesicles; both light up together. The urethra (urinary channel) was left out of the model because it differs between the sexes.
What is known about CBD?
There is no study testing CBD in the human prostate. In the laboratory, in a prostate cell line, CBD reduced inflammatory messengers in cells given an inflammatory stimulus; according to the authors, this effect came from stimulating the CB2 receptor, by suppressing the TLR4/NF-κB pathway. This is a cell experiment; its human equivalent is unknown. According to a review, such findings in reproductive tissues have not yet been supported by clinical studies. There is no study testing CBD in the seminal vesicle: not in humans, not in animals, not in cells. The only thing known here is that two of the targets CBD binds to (CB2 and GPR55) are found in the secretory epithelium of these sacs; no effect can be inferred from this. Piao 2025Cell / labAnimalÜckert 2025ReviewÜckert 2018Human tissue
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? | Prostate | Seminal vesicle | Tissue where it is read the most |
|---|---|---|---|---|
| Receptors | ||||
| CB1 CNR1 | Cannabinoid receptor | 2.2 | 1.4 | cerebral cortex (18.6) |
| CB2 CNR2 | Cannabinoid receptor | 0.1 | 0.0 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 5.3 | 1.5 | liver (21.8) |
| GPR55 | Long an "orphan" receptor · in the cell membrane | 0.1 | 0.2 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 5.3 | 1.7 | adipose tissue (153.2) |
| 5-HT1A HTR1A | Serotonin receptor · in the cell membrane | 0.0 | 0.0 | hippocampal formation (6.1) |
| TRPV2 | Relative of TRPV1 · ion channel | 5.7 | 2.4 | lung (29.5) |
| Endocannabinoid enzymes | ||||
| NAPE-PLD NAPEPLD | Makes anandamide | 4.2 | 3.2 | kidney (13.9) |
| FAAH | Breaks down anandamide | 44.8 | 6.7 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 1.8 | 1.7 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 5.3 | 4.2 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 24.3 | 25.4 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 5.2 | 13.5 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 33.2 | 37.5 | epididymis (125.2) |
| Enzymes that break down CBD and THC | ||||
| CYP3A4 | Breaks down CBD and THC | 0.1 | 0.0 | liver (3,367.1) |
| CYP2C19 | Breaks down CBD | 0.0 | 0.0 | liver (178.0) |
| CYP2C9 | Breaks down THC | 0.0 | 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. 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
- Prostate
- Prostate · MeSH D011467 · UBERON 0002367 · Wikidata Q9625
- Seminal Vesicles
- Seminal Vesicles · MeSH D012669 · UBERON 0000998 · Wikidata Q217259
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Prostate and seminal vesicles: the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/prostat/
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 17 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
- Ruiz-Llorente L, Sánchez MG, Carmena MJ et al. Expression of functionally active cannabinoid receptor CB1 in the human prostate gland. Prostate. 2003;54(2):95-102. PMID 12497582 · doi:10.1002/pros.10165 Human tissue
- Czifra G, Varga A, Nyeste K et al. Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma. J Cancer Res Clin Oncol. 2009;135(4):507-14. PMID 18830626 · doi:10.1007/s00432-008-0482-3 Human tissue
- Gratzke C, Weinhold P, Reich O et al. Transient receptor potential A1 and cannabinoid receptor activity in human normal and hyperplastic prostate: relation to nerves and interstitial cells. Eur Urol. 2010;57(5):902-10. PMID 19733001 · doi:10.1016/j.eururo.2009.08.019 Human tissue
- Thors L, Bergh A, Persson E et al. Fatty acid amide hydrolase in prostate cancer: association with disease severity and outcome, CB1 receptor expression and regulation by IL-4. PLoS One. 2010;5(8):e12275. PMID 20808855 · doi:10.1371/journal.pone.0012275 Human tissueCell / lab
- Endsley MP, Thill R, Choudhry I et al. Expression and function of fatty acid amide hydrolase in prostate cancer. Int J Cancer. 2008;123(6):1318-26. PMID 18566995 · doi:10.1002/ijc.23674 Human tissueCell / lab
- Sánchez MG, Sánchez AM, Collado B et al. Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue. Eur J Pharmacol. 2005;515(1-3):20-7. PMID 15913603 · doi:10.1016/j.ejphar.2005.04.010 Human tissueCell / lab
- Tokanovic S, Malone DT, Ventura S. Stimulation of epithelial CB1 receptors inhibits contractions of the rat prostate gland. Br J Pharmacol. 2007;150(2):227-34. PMID 17099718 · doi:10.1038/sj.bjp.0706952 Animal
- Ückert S, Hedlund P, Tsikas D, Kuczyk MA. The significance of endocannabinoid receptors and endocannabinoids in the lower urinary and genital tract. World J Urol. 2025;44(1):26. PMID 41351769 · doi:10.1007/s00345-025-06045-x Review
- Chung SC, Hammarsten P, Josefsson A et al. A high cannabinoid CB(1) receptor immunoreactivity is associated with disease severity and outcome in prostate cancer. Eur J Cancer. 2009;45(1):174-82. PMID 19056257 · doi:10.1016/j.ejca.2008.10.010 Human tissue
- Cipriano M, Häggström J, Hammarsten P, Fowler CJ. Association between cannabinoid CB1 receptor expression and Akt signalling in prostate cancer. PLoS One. 2013;8(6):e65798. PMID 23755281 · doi:10.1371/journal.pone.0065798 Human tissue
- Ückert S, la Croce G, Bettiga A et al. Expression and distribution of key proteins of the endocannabinoid system in the human seminal vesicles. Andrologia. 2018;50(2):e12875. PMID 28786134 · doi:10.1111/and.12875 Human tissue
- Nomura DK, Lombardi DP, Chang JW et al. Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer. Chem Biol. 2011;18(7):846-56. PMID 21802006 · doi:10.1016/j.chembiol.2011.05.009 Cell / lab
- Alhouayek M, Stafberg L, Karlsson J, Bergström SH, Fowler CJ. Effects of orthotopic implantation of rat prostate tumour cells upon components of the N-acylethanolamine and monoacylglycerol signalling systems: an mRNA study. Sci Rep. 2020;10(1):6314. PMID 32286386 · doi:10.1038/s41598-020-63198-y AnimalCell / lab
- Schuel H, Burkman LJ, Lippes J et al. N-Acylethanolamines in human reproductive fluids. Chem Phys Lipids. 2002;121(1-2):211-27. PMID 12505702 · doi:10.1016/s0009-3084(02)00158-5 Human tissueReview
- Piao JJ, Kim S, Shin D et al. Cannabidiol Alleviates Chronic Prostatitis and Chronic Pelvic Pain Syndrome via CB2 Receptor Activation and TRPV1 Desensitization. World J Mens Health. 2025;43(1):228-238. PMID 38449457 · doi:10.5534/wjmh.230352 Cell / labAnimal
- 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