Pituitary gland and the endocannabinoid system
Hormone release and the stress axis.
Hormone release and the stress axis. 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.
Hormone glandsCB1 high · 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.
Pituitary gland: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 RNA is close to that of the cerebral cortex (18.6) and about twice that of the hypothalamus (9.0); CB2 was not measured. Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 17.3 | high |
| CB2 | CNR2 | 0 | very low |
What does it do there?
CB1 receptor RNA is measured at high levels in the pituitary gland, close to the level in the cerebral cortex. In human pituitary tissue, CB1 was found mostly in hormone cells called corticotrophs and in folliculostellate (star-shaped) cells; it was also present in some of the cells that release prolactin and growth hormone. Researchers think this may be related to control of the stress response. Endocannabinoids (anandamide and 2-AG) have also been measured in the human pituitary. Human Protein AtlasHuman tissueYasuo 2010Human tissuePagotto 2001Human tissueCell / lab
According to reviews, CB1 is found in the hypothalamus and pituitary; stimulating it affects the axes that run from the hypothalamus to the body's hormone glands. In rat anterior pituitary tissue, anandamide reduced the release of TSH, the hormone of the thyroid axis; a substance that blocks CB1 prevented this. In mice without CB1, the stress axis was overactive. The pituitary's share in this is unclear: in one study, pituitary cells from these mice released more ACTH in response to stimulation, while another study found no difference. Pagotto 2006Reviewda Veiga 2008AnimalCell / labWenger 1999AnimalCota 2007AnimalBarna 2004Animal
Student level: terms and cell types
In the human pituitary, in situ hybridization and immunohistochemistry detected CB1 in corticotrophs, mammotrophs, somatotrophs and folliculostellate cells of the anterior lobe. In another study, double immunofluorescence showed CB1 in the pars distalis mainly in corticotrophs and S-100-positive folliculostellate cells; it was absent from gonadotrophs and thyrotrophs. The same study showed endocannabinoid synthesizing and degrading enzymes (DAGLα, NAPE-PLD, MAGL) and 2-AG in the pars tuberalis; the authors considered corticotrophs and folliculostellate cells the main targets of endocannabinoids. Anandamide and 2-AG were measured in the normal human pituitary. Human Protein AtlasHuman tissueYasuo 2010Human tissuePagotto 2001Human tissueCell / lab
According to a review, CB1 activation regulates all hypothalamic–peripheral endocrine axes. In rat anterior pituitary explants, anandamide reduced TSH release, and the CB1 antagonist AM251 blocked this; in the rat anterior lobe, CB1 was in lactotrophs and LH-releasing gonadotrophs (a different distribution from that in humans). In CB1−/− mice, the circadian peak of the HPA axis was enhanced, and pituitary cells gave higher ACTH responses to CRH and forskolin; in another CB1−/− study, however, ACTH release from anterior pituitary fragments was the same across genotypes, and the authors proposed that the effect works through central CB1. Pagotto 2006Reviewda Veiga 2008AnimalCell / labWenger 1999AnimalCota 2007AnimalBarna 2004Animal
Expert level: method notes and numbers
Pituitary gland: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 RNA is close to that of the cerebral cortex (18.6) and about twice that of the hypothalamus (9.0); CB2 was not measured. Human Protein AtlasHuman tissue
Method note
Yasuo 2010: human pars tuberalis and pars distalis; immunohistochemistry, double immunofluorescence (hormone antibodies, S-100), HPLC-MS/MS; sample size not given in the abstract. Pagotto 2001: in situ hybridization and anti-CB1 immunohistochemistry; normal pituitary and 42 pituitary adenomas (findings from adenoma cultures are not used here). Wenger 1999: male Sprague-Dawley rats, immunocytochemistry with CB1 and CB2 antibodies; no CB2 anywhere in the pituitary. Yasuo 2010Human tissuePagotto 2001Human tissueCell / labWenger 1999Animal
da Veiga 2008: Wistar rats; in anterior pituitary explants, 10⁻⁷ M anandamide reduced TSH release, and AM251 blocked this; in live rats, a single dose of anandamide lowered TSH by 42% at 2 hours. Cota 2007 and Barna 2004: CB1−/− mice; the findings at the pituitary level diverge. da Veiga 2008AnimalCell / labCota 2007AnimalBarna 2004Animal
What is known about CBD?
In a small double-blind, placebo-controlled study in 11 healthy male volunteers, a single dose of CBD did not change blood levels of the pituitary hormones prolactin and growth hormone. This is a hormone measurement finding, not a treatment result. Zuardi 1993Human · clinical study
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 | 17.3 | cerebral cortex (18.6) |
| CB2 CNR2 | Cannabinoid receptor | 0.0 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 5.0 | liver (21.8) |
| GPR55 | Long an "orphan" receptor · in the cell membrane | 0.4 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 0.5 | 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 | 1.6 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 1.2 | kidney (13.9) |
| FAAH | Breaks down anandamide | 18.8 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 2.2 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 4.2 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 11.9 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 17.2 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 35.0 | epididymis (125.2) |
| Enzymes that break down CBD and THC | |||
| CYP3A4 | Breaks down CBD and THC | 0.2 | 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
- Pituitary gland
- Pituitary Gland · MeSH D010902 · UBERON 0000007 · Wikidata Q156871
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Pituitary gland and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/hipofiz/
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 10 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
- Yasuo S, Unfried C, Kettner M et al. Localization of an endocannabinoid system in the hypophysial pars tuberalis and pars distalis of man. Cell Tissue Res. 2010;342(2):273-81. PMID 20957495 · doi:10.1007/s00441-010-1066-5 Human tissue
- Pagotto U, Marsicano G, Fezza F et al. Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: first evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level. J Clin Endocrinol Metab. 2001;86(6):2687-96. PMID 11397872 · doi:10.1210/jcem.86.6.7565 Human tissueCell / lab
- Pagotto U, Marsicano G, Cota D et al. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev. 2006;27(1):73-100. PMID 16306385 · doi:10.1210/er.2005-0009 Review
- da Veiga MA, Fonseca Bloise F, Costa-E-Sousa RH et al. Acute effects of endocannabinoid anandamide and CB1 receptor antagonist, AM251 in the regulation of thyrotropin secretion. J Endocrinol. 2008;199(2):235-42. PMID 18755884 · doi:10.1677/JOE-08-0380 AnimalCell / lab
- Wenger T, Fernández-Ruiz JJ, Ramos JA. Immunocytochemical demonstration of CB1 cannabinoid receptors in the anterior lobe of the pituitary gland. J Neuroendocrinol. 1999;11(11):873-8. PMID 10520138 · doi:10.1046/j.1365-2826.1999.00402.x Animal
- Cota D, Steiner MA, Marsicano G et al. Requirement of cannabinoid receptor type 1 for the basal modulation of hypothalamic-pituitary-adrenal axis function. Endocrinology. 2007;148(4):1574-81. PMID 17194743 · doi:10.1210/en.2005-1649 Animal
- Barna I, Zelena D, Arszovszki AC, Ledent C. The role of endogenous cannabinoids in the hypothalamo-pituitary-adrenal axis regulation: in vivo and in vitro studies in CB1 receptor knockout mice. Life Sci. 2004;75(24):2959-70. PMID 15454346 · doi:10.1016/j.lfs.2004.06.006 Animal
- Zuardi AW, Guimarães FS, Moreira AC. Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteers. Braz J Med Biol Res. 1993;26(2):213-7. PMID 8257923 Human · clinical study
- 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