Bone and bone marrow: the endocannabinoid system
Bone renewal and blood formation.
Bone renewal and blood formation. 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.
Immune system and blood formationCB1 very low · CB2 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.
Bone marrow: RNA level of the receptor gene in human tissue (tissue consensus data). HPA does not measure bone tissue; the value is for bone marrow. Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 0.3 | very low |
| CB2 | CNR2 | 1.3 | low |
What does it do there?
Bone is constantly renewed: bone-building cells lay down new bone, and bone-resorbing cells remove the old. Both of these cell types carry the CB2 receptor and make their own endocannabinoids. In mice lacking CB2, age-related bone loss sped up markedly; in humans, too, certain variations in the CB2 gene were found to be associated with postmenopausal osteoporosis. Saponaro 2021ReviewBab and Zimmer 2008ReviewOfek 2006AnimalCell / labWhyte 2012Cell / labKarsak 2005Human · genetic study
One of bone's jobs is also making blood. In the bone marrow, the stem cells that produce blood cells carry CB1 and CB2, while the mesenchymal stem cells in the marrow release endocannabinoids. In the laboratory, endocannabinoids stimulated the migration of blood stem cells, and substances that block the receptors stopped this. Saponaro 2021ReviewKöse 2018Human tissueCell / labValk 1997Cell / lab
Student level: terms and cell types
In bone remodeling, osteoblasts make new bone and osteoclasts resorb the old. Osteoblasts and osteoclasts produce anandamide and 2-AG and carry CB2 (CB2 has also been shown in osteocytes); human osteoclasts carry CB1 and CB2, and nanomolar anandamide increased bone resorption by these cells. In CB2−/− mice, age-related trabecular bone loss sped up markedly and osteoclast numbers rose. In a genetic association study comparing women with postmenopausal osteoporosis and matched controls, single-nucleotide variants in the CNR2 region were significantly associated; there was no convincing association for CNR1. Saponaro 2021ReviewBab and Zimmer 2008ReviewOfek 2006AnimalCell / labWhyte 2012Cell / labKarsak 2005Human · genetic study
Bone marrow mesenchymal stem cells from healthy donors secreted anandamide and 2-AG; CD34+ hematopoietic stem cells and bone marrow mononuclear cells carried CB1 and CB2, while mesenchymal stem cells did not. Receptor antagonists blocked the stem cell migration stimulated by endocannabinoids. In the laboratory, anandamide markedly strengthened the proliferative effect of IL-3 on mouse bone marrow cells; on its own it had no effect. Saponaro 2021ReviewKöse 2018Human tissueCell / labValk 1997Cell / lab
Expert level: method notes and numbers
Bone marrow: RNA level of the receptor gene in human tissue (tissue consensus data). HPA does not measure bone tissue; the value is for bone marrow. Human Protein AtlasHuman tissue
Method note
Ofek 2006: CB2−/− mice; trabecular loss and cortical expansion, increased osteoclast numbers; a CB2-specific agonist reduced ovariectomy-induced bone loss (mouse). Karsak 2005: women with postmenopausal osteoporosis and matched controls, genetic case–control; single SNP P = 0.0014, haplotype P = 0.0001 (sample size not in the abstract). Whyte 2012: human osteoclasts differentiated from monocytes; nanomolar AEA, CP 55 940 and JWH015 increased bone resorption, and CB1/CB2 antagonists reduced it. Ofek 2006AnimalCell / labKarsak 2005Human · genetic studyWhyte 2012Cell / lab
Köse 2018: healthy donors with and without G-CSF; qRT-PCR, flow cytometry, in vitro migration assay (sample size not in the abstract). Valk 1997: Cb2 mRNA in 45 of 51 blood cell lines; anandamide effective at 0.1–0.3 µmol/L. Bab and Zimmer 2008: CB1 on sympathetic nerve endings in bone suppresses noradrenaline release. Köse 2018Human tissueCell / labValk 1997Cell / labBab and Zimmer 2008Review
The model shows the thigh bones and hip bones; the pin is on the wing of the hip bone, where bone marrow is abundant in adults.
What is known about CBD?
In the laboratory, CBD increased the expression of an enzyme involved in cross-linking collagen fibers in cultures of bone-building cells (osteoblasts). When human blood stem cells were grown in a CBD-containing medium for 28 days, early B cell precursors rose markedly; the researchers wrote that safety in this respect needs further study. These are cell experiment findings. Kogan 2015AnimalCell / labKhan 2026Cell / lab
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 | 0.3 | cerebral cortex (18.6) |
| CB2 CNR2 | Cannabinoid receptor | 1.3 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 0.9 | liver (21.8) |
| GPR55 | Long an "orphan" receptor · in the cell membrane | 0.2 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 2.2 | 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 | 21.5 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 1.9 | kidney (13.9) |
| FAAH | Breaks down anandamide | 9.8 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 0.3 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 14.2 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 15.3 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 0.8 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 25.0 | 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 | 0.1 | liver (178.0) |
| CYP2C9 | Breaks down THC | 0.1 | 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
- Bone and Bones
- Bone and Bones · MeSH D001842 · UBERON 0001474 · Wikidata Q265868
- Bone Marrow
- Bone Marrow · MeSH D001853 · UBERON 0002371 · Wikidata Q546523
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Bone and bone marrow: the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/kemik/
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 11 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
- Saponaro F, Ferrisi R, Gado F et al. The Role of Cannabinoids in Bone Metabolism: A New Perspective for Bone Disorders. Int J Mol Sci. 2021;22(22):12374. PMID 34830256 · doi:10.3390/ijms222212374 Review
- Bab I, Zimmer A. Cannabinoid receptors and the regulation of bone mass. Br J Pharmacol. 2008;153(2):182-8. PMID 18071301 · doi:10.1038/sj.bjp.0707593 Review
- Ofek O, Karsak M, Leclerc N et al. Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci U S A. 2006;103(3):696-701. PMID 16407142 · doi:10.1073/pnas.0504187103 AnimalCell / lab
- Whyte LS, Ford L, Ridge SA et al. Cannabinoids and bone: endocannabinoids modulate human osteoclast function in vitro. Br J Pharmacol. 2012;165(8):2584-97. PMID 21649637 · doi:10.1111/j.1476-5381.2011.01519.x Cell / lab
- Karsak M, Cohen-Solal M, Freudenberg J et al. Cannabinoid receptor type 2 gene is associated with human osteoporosis. Hum Mol Genet. 2005;14(22):3389-96. PMID 16204352 · doi:10.1093/hmg/ddi370 Human · genetic study
- Köse S, Aerts-Kaya F, Köprü ÇZ et al. Human bone marrow mesenchymal stem cells secrete endocannabinoids that stimulate in vitro hematopoietic stem cell migration effectively comparable to beta-adrenergic stimulation. Exp Hematol. 2018;57:30-41.e1. PMID 29030083 · doi:10.1016/j.exphem.2017.09.009 Human tissueCell / lab
- Valk P, Verbakel S, Vankan Y et al. Anandamide, a natural ligand for the peripheral cannabinoid receptor is a novel synergistic growth factor for hematopoietic cells. Blood. 1997;90(4):1448-57. PMID 9269762 · doi:10.1182/blood.V90.4.1448 Cell / lab
- Kogan NM, Melamed E, Wasserman E et al. Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts. J Bone Miner Res. 2015;30(10):1905-13. PMID 25801536 · doi:10.1002/jbmr.2513 AnimalCell / lab
- Khan DMIO, Crawford RB, Kaminski NE. Cannabidiol and Δ9-tetrahydrocannabinol alter human hematopoiesis by enhancing B cell lineage commitment. Toxicology. 2026;526:154537. PMID 42419677 · doi:10.1016/j.tox.2026.154537 Cell / lab
- 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