Adrenal gland and the endocannabinoid system
Stress hormones.
Stress hormones. 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 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.
Adrenal gland: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 at moderate levels; CB2 was not measured. Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 4.6 | moderate |
| CB2 | CNR2 | 0 | very low |
What does it do there?
The adrenal gland makes hormones that are released during stress: its outer layer (the cortex) makes steroid hormones, and its inner part (the medulla) makes adrenaline. CB1 was found in the human adrenal cortex, but CB2 was not. In the lab, anandamide reduced the release of steroid hormones from human adrenal cortex cells; a substance that blocks CB1 reversed this effect. In rabbits, cannabinoids reduced adrenaline release; but no CB1 was found in the gland itself, and researchers think the effect comes from the nerve endings that stimulate the gland. Human Protein AtlasHuman tissueZiegler 2010Human tissueCell / labNiederhoffer 2001AnimalCell / lab
The stress axis runs from the brain to the pituitary gland and from there to the adrenal gland. In mice, blocking CB1 markedly amplified the stress-induced rise in stress hormone; substances that strengthen endocannabinoid signaling reduced or eliminated this rise. In rats under repeated stress, endocannabinoids played a role in the stress hormone response getting used to the stress over time. According to the authors of a review, this system can both brake and boost the stress axis. Patel 2004AnimalHill 2009AnimalHill 2010AnimalHillard 2016Review
Student level: terms and cell types
CB1 expression was shown in the normal human adrenal gland and in the adrenocortical cell line NCI-H295R; CB2 was absent. Anandamide suppressed basal and stimulated adrenocortical steroid release; the CB1 antagonist SR141716A reversed the effect. In rabbits, WIN55212-2 and CP55940 lowered plasma adrenaline; in the isolated gland, WIN55212-2 suppressed nerve-stimulated adrenaline release. Autoradiography and in situ hybridization detected no CB1 in the gland; the authors interpreted the effect as presynaptic, CB1-mediated suppression of acetylcholine release from preganglionic sympathetic neurons. Human Protein AtlasHuman tissueZiegler 2010Human tissueCell / labNiederhoffer 2001AnimalCell / lab
In male mice, the CB1 antagonist SR141716 given before restraint enhanced the stress-induced rise in corticosterone and Fos expression in the PVN; pretreatment with CP55940, AM404 or the FAAH inhibitor URB597 reduced or abolished the stress-induced rise in corticosterone. In rats under repeated stress, anandamide decreased persistently in the corticolimbic circuit, while 2-AG rose only in the amygdala; a CB1 antagonist given before the last stress prevented habituation of the corticosterone response. According to a review, CB1 signaling can both suppress and enhance HPA activation; the authors propose that the suppressive arm speeds the return to baseline after stress. Patel 2004AnimalHill 2009AnimalHill 2010AnimalHillard 2016Review
Expert level: method notes and numbers
Adrenal gland: RNA level of the receptor gene in human tissue (tissue consensus data). CB1 at moderate levels; CB2 was not measured. Human Protein AtlasHuman tissue
Method note
Ziegler 2010: normal human adrenal gland and NCI-H295R cells, RT-PCR; the abstract's methods sentence says cortisol and its results sentence says corticosterone, so the text says "steroid hormones". Niederhoffer 2001: spinalized rabbits and isolated gland; fast-scan cyclic voltammetry; WIN55212-2 0.3–10 µM, SR141716A 1 µM. Ziegler 2010Human tissueCell / labNiederhoffer 2001AnimalCell / lab
Patel 2004: male ICR mice, SR141716 0.01–5 mg/kg, 30-minute restraint, PVN Fos immunohistochemistry. Hill 2010: Sprague-Dawley rats, repeated stress, FAAH inhibition and systemic or intra-amygdala CB1 antagonist; sample size not given in the abstract. Patel 2004AnimalHill 2010Animal
What is known about CBD?
In a small double-blind, placebo-controlled study in 11 healthy male volunteers, cortisol fell naturally during the morning hours with placebo; a single dose of CBD clearly blunted this fall. In a randomized study in 32 volunteers with high paranoid tendencies, however, CBD did not change the rise in salivary cortisol caused by a virtual reality environment. These are small hormone measurement studies, not treatment results. Zuardi 1993Human · clinical studyHundal 2018Human · clinical study
Mixed results Weak evidence
In the guide: Anxiety and CBD
Research results are mixed. It has not been proven that CBD works for this. If you are considering CBD, you can talk with your doctor or pharmacist, including about the medicines you take.
No effect found Weak evidence
In the guide: PTSD and CBD
Research has not found that CBD helps with this condition. 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.
| Gene | What does it do? | Here | Tissue where it is read the most |
|---|---|---|---|
| Receptors | |||
| CB1 CNR1 | Cannabinoid receptor | 4.6 | cerebral cortex (18.6) |
| CB2 CNR2 | Cannabinoid receptor | 0.0 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 4.4 | liver (21.8) |
| GPR55 | Long an "orphan" receptor · in the cell membrane | 0.0 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 3.8 | 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 | 19.7 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 4.4 | kidney (13.9) |
| FAAH | Breaks down anandamide | 14.3 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 1.0 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 15.2 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 15.2 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 13.2 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 28.8 | epididymis (125.2) |
| Enzymes that break down CBD and THC | |||
| CYP3A4 | Breaks down CBD and THC | 3.4 | 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
- Adrenal gland
- Adrenal Glands · MeSH D000311 · UBERON 0002369 · Wikidata Q712294
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Adrenal gland and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/bobrekustu/
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
- Ziegler CG, Mohn C, Lamounier-Zepter V et al. Expression and function of endocannabinoid receptors in the human adrenal cortex. Horm Metab Res. 2010;42(2):88-92. PMID 19862666 · doi:10.1055/s-0029-1241860 Human tissueCell / lab
- Niederhoffer N, Hansen HH, Fernandez-Ruiz JJ, Szabo B. Effects of cannabinoids on adrenaline release from adrenal medullary cells. Br J Pharmacol. 2001;134(6):1319-27. PMID 11704653 · doi:10.1038/sj.bjp.0704359 AnimalCell / lab
- Patel S, Roelke CT, Rademacher DJ et al. Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis. Endocrinology. 2004;145(12):5431-8. PMID 15331569 · doi:10.1210/en.2004-0638 Animal
- Hill MN, McLaughlin RJ, Morrish AC et al. Suppression of amygdalar endocannabinoid signaling by stress contributes to activation of the hypothalamic-pituitary-adrenal axis. Neuropsychopharmacology. 2009;34(13):2733-45. PMID 19710634 · doi:10.1038/npp.2009.114 Animal
- Hill MN, McLaughlin RJ, Bingham B et al. Endogenous cannabinoid signaling is essential for stress adaptation. Proc Natl Acad Sci U S A. 2010;107(20):9406-11. PMID 20439721 · doi:10.1073/pnas.0914661107 Animal
- Hillard CJ, Beatka M, Sarvaideo J. Endocannabinoid Signaling and the Hypothalamic-Pituitary-Adrenal Axis. Compr Physiol. 2016;7(1):1-15. PMID 28134998 · doi:10.1002/cphy.c160005 Review
- 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
- Hundal H, Lister R, Evans N et al. The effects of cannabidiol on persecutory ideation and anxiety in a high trait paranoid group. J Psychopharmacol. 2018;32(3):276-282. PMID 29086614 · doi:10.1177/0269881117737400 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