Hypothalamus and the endocannabinoid system
Appetite and energy balance.
Appetite and energy balance. 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.
BrainCB1 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.
Hypothalamus: RNA level of the receptor gene in human tissue (tissue consensus data). Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 9 | moderate |
| CB2 | CNR2 | 0 | very low |
What does it do there?
The hypothalamus senses the body's nutritional state and regulates appetite and energy balance; it does this mostly through signals from leptin, a hormone that reduces appetite. In human brains examined after death, nerve cells in the hypothalamus carried moderate amounts of the building instructions (mRNA) for CB1. In mice, CB1 was found in hypothalamic cells that make substances regulating appetite. Di Marzo 2001AnimalWestlake 1994Human tissueCota 2003AnimalCell / lab
According to animal experiments, endocannabinoids in the hypothalamus may be part of the circuit that keeps appetite going: leptin reduced them, and their levels were high in obese mice and rats with faulty leptin signaling. Anandamide given into the hypothalamus increased eating in well-fed rats; mice without CB1 ate less and stayed leaner. In mice, stimulating CB1 pushed POMC cells, which normally create a feeling of fullness, to release β-endorphin, which increases eating. Di Marzo 2001AnimalJamshidi and Taylor 2001AnimalCota 2003AnimalCell / labKoch 2015Animal
The hypothalamus is also where the stress response begins: the cells here are the first link in the stress hormone chain (the HPA axis). In rats, stress hormone quickly reduced the excitatory signal reaching these cells; this fast brake depended on endocannabinoid release and CB1, and it did not work when CB1 was blocked with a drug. In other words, the body's own cannabinoids appear to help the stress hormone quickly shut off its own release; this knowledge comes from animal experiments. Di 2003AnimalEvanson 2010Animal
Student level: terms and cell types
The hypothalamus senses nutritional state mainly through leptin; leptin increases appetite-suppressing neuropeptides such as α-MSH and decreases appetite-stimulating factors, above all neuropeptide Y. The hypothalamus contains CB1 and two endocannabinoids, anandamide and 2-AG. In postmortem human brain, in situ hybridization detected moderate levels of CB1 mRNA in hypothalamic neurons. In mice, hypothalamic CB1 mRNA is found in the same cells as neuropeptides that regulate food intake, such as CRH, CART, MCH and preproorexin. Di Marzo 2001AnimalWestlake 1994Human tissueCota 2003AnimalCell / lab
In db/db and ob/ob mice and Zucker rats with faulty leptin signaling, endocannabinoid levels were high in the hypothalamus (not in the cerebellum); acute leptin lowered hypothalamic anandamide and 2-AG. In satiated rats, anandamide given into the ventromedial hypothalamus caused overeating (hyperphagia), and pretreatment with the CB1 antagonist SR141716 reduced it. CB1−/− mice ate less and were lean; CRH mRNA increased in the paraventricular nucleus, and CART mRNA decreased in the dorsomedial and lateral hypothalamus. In mice, CB1 activation paradoxically increased the activity of satiety-promoting POMC neurons and selectively raised the release of β-endorphin, not α-MSH; the opioid antagonist naloxone blocked CB1-induced acute feeding. Di Marzo 2001AnimalJamshidi and Taylor 2001AnimalCota 2003AnimalCell / labKoch 2015Animal
In rat hypothalamic slices (whole-cell recording), dexamethasone and corticosterone rapidly suppressed glutamatergic input to parvocellular neuroendocrine cells in the paraventricular nucleus (PVN); the effect was also seen with membrane-impermeant (albumin-bound) dexamethasone, was not seen with glucocorticoid applied inside the cell, and was completely abolished by the CB1 antagonists AM251 and AM281 (retrograde endocannabinoid release). In live rats, dexamethasone given into the PVN rapidly lowered the restraint stress–induced rise in ACTH and corticosterone; AM251 blocked this fast feedback, and stress increased hypothalamic 2-AG. Di 2003AnimalEvanson 2010Animal
Expert level: method notes and numbers
Hypothalamus: RNA level of the receptor gene in human tissue (tissue consensus data). In the HPA brain region data (hypothalamus), CB1 is 40.7 nTPM; the two datasets come from different samples and methods, so their numbers cannot be converted into each other directly. Human Protein AtlasHuman tissue
Method note
Westlake 1994: [3H]CP-55,940 autoradiography and in situ hybridization with a human CB1 riboprobe; postmortem brains of elderly people (3 normal, 5 Alzheimer's, 5 other cortical pathology). No numerical value for the hypothalamus is given in the abstract. Cota 2003: CB1−/− mice and wild-type littermates; no genotype difference in energy expenditure, body temperature or locomotor activity. Westlake 1994Human tissueCota 2003AnimalCell / lab
Di Marzo 2001: CB1−/− mice, SR141716A; obese db/db and ob/ob mice and Zucker rats; acute leptin in normal rats. Jamshidi and Taylor 2001: Wistar rats, 50 ng anandamide into the ventromedial hypothalamus; significant hyperphagia over 3 hours, attenuated by SR141716 pretreatment (P < 0.001). Koch 2015: mice; chemogenetic (DREADD) inhibition of POMC neurons reduced CB1-induced feeding, and their activation increased it. Di Marzo 2001AnimalJamshidi and Taylor 2001AnimalKoch 2015Animal
What is known about CBD?
In two randomized, placebo-controlled studies in Lennox–Gastaut syndrome, decreased appetite was among the most common side effects in people taking CBD (along with sleepiness and diarrhea); these studies did not examine whether it was related to the hypothalamus. Devinsky 2018Human · clinical studyThiele 2018Human · clinical study
In rats, CBD given directly into the side part of the hypothalamus (the lateral hypothalamus) increased daytime wakefulness and reduced deep sleep and REM sleep. This is an animal experiment with delivery directly into the brain; it does not count as evidence for how CBD taken by mouth affects sleep in humans. Murillo-Rodríguez 2008Animal
No effect found Insufficient evidence
In the guide: Diabetes and CBD
Research has not shown that CBD helps with this. If you are considering CBD, you can talk with your doctor or pharmacist, including about the medicines you take.
No effect found Insufficient evidence
In the guide: Appetite Loss in Cancer and CBD
Research has not found that CBD helps with this condition. CBD can interact with some cancer medicines; if you are considering it, you can talk with your oncologist and pharmacist first.
Not studied enough Very weak evidence
In the guide: Loss of Appetite, Weight Loss and CBD
It is not known whether CBD oil helps with loss of appetite and weight loss; there are very few studies, and CBD can lower appetite in some people. The positive results come from prescription medicines containing THC; their effect on weight is small and the evidence is weak. 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 | 9.0 | cerebral cortex (18.6) |
| CB2 CNR2 | Cannabinoid receptor | 0.0 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 5.6 | liver (21.8) |
| GPR55 | Long an "orphan" receptor · in the cell membrane | 0.3 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 1.5 | adipose tissue (153.2) |
| 5-HT1A HTR1A | Serotonin receptor · in the cell membrane | 1.4 | hippocampal formation (6.1) |
| TRPV2 | Relative of TRPV1 · ion channel | 8.2 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 1.5 | kidney (13.9) |
| FAAH | Breaks down anandamide | 19.9 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 2.9 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 6.5 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 29.6 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 12.9 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 60.1 | 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
- Hypothalamus
- Hypothalamus · MeSH D007031 · UBERON 0001898 · Wikidata Q164386
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Hypothalamus and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/hipotalamus/
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 12 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
- Di Marzo V, Goparaju SK, Wang L et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001;410(6830):822-5. PMID 11298451 · doi:10.1038/35071088 Animal
- Westlake TM, Howlett AC, Bonner TI et al. Cannabinoid receptor binding and messenger RNA expression in human brain: an in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer's brains. Neuroscience. 1994;63(3):637-52. PMID 7898667 · doi:10.1016/0306-4522(94)90511-8 Human tissue
- Cota D, Marsicano G, Tschöp M et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest. 2003;112(3):423-31. PMID 12897210 · doi:10.1172/JCI17725 AnimalCell / lab
- Jamshidi N, Taylor DA. Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. Br J Pharmacol. 2001;134(6):1151-4. PMID 11704633 · doi:10.1038/sj.bjp.0704379 Animal
- Koch M, Varela L, Kim JG et al. Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature. 2015;519(7541):45-50. PMID 25707796 · doi:10.1038/nature14260 Animal
- Di S, Malcher-Lopes R, Halmos KC, Tasker JG. Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. J Neurosci. 2003;23(12):4850-7. PMID 12832507 · doi:10.1523/JNEUROSCI.23-12-04850.2003 Animal
- Evanson NK, Tasker JG, Hill MN, Hillard CJ, Herman JP. Fast feedback inhibition of the HPA axis by glucocorticoids is mediated by endocannabinoid signaling. Endocrinology. 2010;151(10):4811-9. PMID 20702575 · doi:10.1210/en.2010-0285 Animal
- Devinsky O, Patel AD, Cross JH et al. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018;378(20):1888-1897. PMID 29768152 · doi:10.1056/NEJMoa1714631 Human · clinical study
- Thiele EA, Marsh ED, French JA et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10125):1085-1096. PMID 29395273 · doi:10.1016/S0140-6736(18)30136-3 Human · clinical study
- Murillo-Rodríguez E, Millán-Aldaco D, Palomero-Rivero M, Mechoulam R, Drucker-Colín R. The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent. Behav Neurosci. 2008;122(6):1378-82. PMID 19045957 · doi:10.1037/a0013278 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