Cerebral cortex and the endocannabinoid system
Thinking, language and perception.
Thinking, language and perception. 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.
Cerebral cortex: RNA level of the receptor gene in human tissue (tissue consensus data). The tissue where CB1 is measured highest. Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 18.6 | high |
| CB2 | CNR2 | 0 | very low |
What does it do there?
In the human brain, the CB1 receptor is found in every region of the cerebral cortex, but its density varies from place to place. It is densest in the "association" areas of the frontal and limbic lobes, where higher-level thinking takes place, and sparsest in the primary sensory and motor areas. It is also relatively high in regions of the left hemisphere linked to language. Glass 1997Human tissueEggan and Lewis 2007Human tissueAnimal
In the cortex, CB1 is found mostly on the terminals of interneurons that act as a brake (they release GABA); in monkeys and rats, most of these cells belong to a group that carries cholecystokinin (CCK). In mouse brain slices, when the main nerve cells (pyramidal cells) were stimulated, they released endocannabinoids, which briefly loosened the brake coming from these terminals. Researchers think this arrangement may play an important role in the circuits that support thinking. Eggan and Lewis 2007Human tissueAnimalEggan 2010AnimalBodor 2005AnimalTrettel and Levine 2003Animal
Student level: terms and cell types
In human brain sections, [3H]CP55,940 binding was present in all regions of the neocortex and varied with the cortical hierarchy: highest in the association areas of the frontal and limbic lobes, intermediate in secondary sensory and motor areas, and lowest in primary sensory and motor areas. Relatively high density was consistently seen in regions of the left (dominant) hemisphere associated with verbal language functions. Across the layers there were two densest bands: lamina I at the surface and laminae V–VI deeper down. Immunocytochemistry in macaque and human neocortex also showed that CB1-positive axons were denser in association areas, such as the prefrontal and cingulate cortex, than in primary areas. Glass 1997Human tissueEggan and Lewis 2007Human tissueAnimal
In perfused macaque prefrontal cortex, electron microscopy showed CB1 mainly on axon terminals forming only symmetric (inhibitory) synapses; in the macaque dorsolateral prefrontal cortex, 91% of CB1-positive neurons were CCK-positive. In rat somatosensory cortex, membrane CB1 was found only on GABA-containing terminals forming symmetric synapses; two-thirds of CB1-positive cells carried CCK and one-third carried calbindin. In mouse sensory cortex, repeated depolarization of layer 2/3 pyramidal neurons caused a transient depolarization-induced suppression of inhibition (DSI), expressed as reduced presynaptic GABA release; the CB1 antagonist AM251 blocked it. Eggan and Lewis 2007Human tissueAnimalEggan 2010AnimalBodor 2005AnimalTrettel and Levine 2003Animal
Expert level: method notes and numbers
Cerebral cortex: RNA level of the receptor gene in human tissue (tissue consensus data). The tissue where CB1 is measured highest. In the HPA brain region data (cerebral cortex), CB1 is 45.5 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
Glass 1997: quantitative receptor autoradiography of sections labeled in vitro with [3H]CP55,940; human brains: 1 fetus (33rd week of gestation), 2 infants (3–6 months), 8 adults (21–81 years). In association areas, there was also a narrow band in the middle of lamina IV. Glass 1997Human tissue
Eggan and Lewis 2007: macaque (Macaca fascicularis) and postmortem human neocortex; immunocytochemistry with antibodies specific to the N- or C-terminus of CB1, electron microscopy in macaque. Eggan 2010: in macaque DLPFC, 51% of CCK-IR neurons were CB1-positive; synapses of CB1-positive terminals were symmetric, with dendritic shafts as the main targets (81–88%). Eggan and Lewis 2007Human tissueAnimalEggan 2010Animal
Bodor 2005: Wistar rats, multiple immunolabeling and whole-cell recording; large pyramidal cells in layer VB received far fewer inputs from CB1-containing terminals and showed no DSI. Trettel and Levine 2003: mouse cortical slices; WIN55,212-2 reduced evoked IPSC amplitude and occluded DSI. Bodor 2005AnimalTrettel and Levine 2003Animal
What is known about CBD?
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.
Not studied enough Insufficient evidence
In the guide: Spasticity Other Than MS and CBD
There is not enough research in humans. It is not known whether CBD works. If you are considering CBD, you can talk with your doctor or pharmacist, including about the medicines you take.
Not studied enough Insufficient evidence
In the guide: ADHD and CBD
CBD oil has not yet been tested in a controlled study in ADHD; the only small study, with a THC-containing spray, showed no clear difference. It is not known whether CBD helps ADHD. If you are considering CBD for yourself or your child, you can talk with your doctor or pharmacist, including about the medicines being taken.
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 | 18.6 | cerebral cortex (18.6) |
| CB2 CNR2 | Cannabinoid receptor | 0.0 | spleen (8.4) |
| TRPV1 | Heat and chili pepper sensor · ion channel | 5.8 | liver (21.8) |
| GPR55 | Long an "orphan" receptor · in the cell membrane | 0.6 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 2.9 | adipose tissue (153.2) |
| 5-HT1A HTR1A | Serotonin receptor · in the cell membrane | 4.9 | hippocampal formation (6.1) |
| TRPV2 | Relative of TRPV1 · ion channel | 4.9 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 11.3 | kidney (13.9) |
| FAAH | Breaks down anandamide | 20.5 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 12.3 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 11.9 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 120.9 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 21.5 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 80.5 | 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
- Cerebral cortex
- Cerebral Cortex · MeSH D002540 · UBERON 0000956 · Wikidata Q75839
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Cerebral cortex and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/kabuk/
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
- Glass M, Dragunow M, Faull RL. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience. 1997;77(2):299-318. PMID 9472392 · doi:10.1016/s0306-4522(96)00428-9 Human tissue
- Eggan SM, Lewis DA. Immunocytochemical distribution of the cannabinoid CB1 receptor in the primate neocortex: a regional and laminar analysis. Cereb Cortex. 2007;17(1):175-91. PMID 16467563 · doi:10.1093/cercor/bhj136 Human tissueAnimal
- Eggan SM, Melchitzky DS, Sesack SR et al. Relationship of cannabinoid CB1 receptor and cholecystokinin immunoreactivity in monkey dorsolateral prefrontal cortex. Neuroscience. 2010;169(4):1651-61. PMID 20542094 · doi:10.1016/j.neuroscience.2010.06.011 Animal
- Bodor AL, Katona I, Nyíri G et al. Endocannabinoid signaling in rat somatosensory cortex: laminar differences and involvement of specific interneuron types. J Neurosci. 2005;25(29):6845-56. PMID 16033894 · doi:10.1523/JNEUROSCI.0442-05.2005 Animal
- Trettel J, Levine ES. Endocannabinoids mediate rapid retrograde signaling at interneuron→pyramidal neuron synapses of the neocortex. J Neurophysiol. 2003;89(4):2334-8. PMID 12686587 · doi:10.1152/jn.01037.2002 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