Hippocampus and the endocannabinoid system
Memory and learning.
Memory and learning. 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 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.
Hippocampal formation: RNA level of the receptor gene in human tissue (tissue consensus data). Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 13.2 | high |
| CB2 | CNR2 | 0 | very low |
What does it do there?
In the hippocampus, the CB1 receptor clusters especially on the terminals of a group of inhibitory (GABA-releasing) nerve cells. At these terminals, endocannabinoids briefly reduce GABA release; the signal travels backward from the receiving cell. Katona 1999AnimalWilson and Nicoll 2001Animal
Researchers think this brake affects the rhythm of the nerve networks in the hippocampus and the cognitive functions that depend on them. Katona 1999AnimalLu and Mackie 2016Review
Student level: terms and cell types
CB1 stains densely in interneurons with a basket-cell appearance across all subfields and layers of the hippocampus; 85.6% of these contain cholecystokinin (CCK), whereas only 4.6% of parvalbumin (PV)-containing basket cells carry CB1. CB1-bearing CCK terminals wrap around the cell bodies and proximal dendrites of pyramidal neurons. When a pyramidal neuron depolarizes, the transient suppression of GABAergic transmission (DSI) occurs through backward (retrograde) signaling by endocannabinoids released from the receiving cell. Katona 1999AnimalWilson and Nicoll 2001Animal
Reduced GABA release from these terminals is considered the likely mechanism by which the body's own CB1 ligands and those taken from outside interfere with hippocampal network oscillations and the cognitive functions linked to them. Katona 1999AnimalLu and Mackie 2016Review
Expert level: method notes and numbers
Hippocampal formation: RNA level of the receptor gene in human tissue (tissue consensus data). In the HPA brain region data (hippocampal formation), CB1 is 40.3 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
Katona 1999: immunohistochemistry and electron microscopy in rat hippocampus with a newly developed anti-CB1 antibody; electrically evoked [3H]GABA release in superfused slices. WIN 55,212-2 (0.01–3 µM) reduced release in a dose-dependent manner (EC50 0.041 µM); the CB1 antagonist SR 141716A (1 µM) blocked the effect; glutamate blockers (AP5, CNQX) did not reduce the effect. Katona 1999Animal
Wilson and Nicoll 2001: rat hippocampal slices; depolarized neurons rapidly released anandamide and 2-AG in a calcium-dependent manner. Wilson and Nicoll 2001Animal
What is known about CBD?
Strong evidence shows that the approved CBD medicine reduces seizures in Dravet and Lennox–Gastaut syndromes. But this effect does not appear to work through CB1: according to the drug's US label, its mechanism of action is not fully known, and CBD does not appear to exert its anti-seizure effect through cannabinoid receptors. Epidiolex label (FDA)Official drug labelIbeas Bih 2015Review
Proven effect Strong evidence
In the guide: Dravet Syndrome and CBD
The approved CBD medicine reduced seizures in this condition. This result does not apply to CBD oils bought online. CBD can interact with some seizure medicines; if you are considering it for yourself or your child, you can talk with your neurologist first.
Proven effect Strong evidence
In the guide: Lennox–Gastaut Syndrome and CBD
The approved CBD medicine reduced seizures in this condition. This result does not apply to CBD oils bought online. CBD can interact with some seizure medicines; if you are considering it for yourself or your child, you can talk with your neurologist first.
Proven effect Moderate evidence
In the guide: Tuberous Sclerosis and CBD
The approved CBD medicine reduced seizures in this disease; for now, this finding rests on a single large controlled study. This result does not apply to CBD oils bought online. CBD can interact with some seizure medicines; if you are considering it for yourself or your child, you can talk with your neurologist first.
Not studied enough Very weak evidence
In the guide: Dementia, Alzheimer’s and CBD
There is not enough research in people; there are only two small studies with pure CBD. Whether CBD works is not known. 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 | 13.2 | cerebral cortex (18.6) |
| CB2 CNR2 | Cannabinoid receptor | 0.0 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 6.3 | 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 | 3.0 | adipose tissue (153.2) |
| 5-HT1A HTR1A | Serotonin receptor · in the cell membrane | 6.1 | hippocampal formation (6.1) |
| TRPV2 | Relative of TRPV1 · ion channel | 3.5 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 1.9 | kidney (13.9) |
| FAAH | Breaks down anandamide | 24.1 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 4.3 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 5.8 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 69.2 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 25.8 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 94.7 | 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
- Hippocampus
- Hippocampus · MeSH D006624 · Wikidata Q48360
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Hippocampus and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/hipokampus/
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 7 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
- Katona I, Sperlágh B, Sík A et al. Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J Neurosci. 1999;19(11):4544-58. PMID 10341254 · doi:10.1523/JNEUROSCI.19-11-04544.1999 Animal
- Wilson RI, Nicoll RA. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature. 2001;410(6828):588-92. (Correction: Nature. 2001;411(6840):974.) PMID 11279497 · doi:10.1038/35069076 Animal
- Lu HC, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biol Psychiatry. 2016;79(7):516-25. PMID 26698193 · doi:10.1016/j.biopsych.2015.07.028 Review
- EPIDIOLEX (cannabidiol) oral solution, US prescribing information (Jazz Pharmaceuticals), DailyMed setid 8bf27097-4870-43fb-94f0-f3d0871d1eec, SPL version 35 (effective May 29, 2026; on DailyMed June 15, 2026): sections 1, 2.1–2.6, 4, 5.1–5.5, 6.1, 7, 8.1, 8.2, 8.4, 8.5, 8.6, 9.2, 9.3, 11, 12.1, 12.2, 12.3, 13.1, 14.1–14.3, 17. Source Official drug label
- Ibeas Bih C, Chen T, Nunn AV et al. Molecular Targets of Cannabidiol in Neurological Disorders. Neurotherapeutics. 2015;12(4):699-730. PMID 26264914 · doi:10.1007/s13311-015-0377-3 Review
- 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