Amygdala and the endocannabinoid system
Tuning fear and stress.
Tuning fear and stress. 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.
Amygdala: RNA level of the receptor gene in human tissue (tissue consensus data). Human Protein AtlasHuman tissue
| Receptor | Gene | RNA (nTPM) | Level |
|---|---|---|---|
| CB1 | CNR1 | 13.3 | high |
| CB2 | CNR2 | 0 | very low |
What does it do there?
Measurements in the human brain found cannabinoid receptors to be plentiful in the amygdala. One part of the amygdala (the basolateral amygdala) plays an important role in noticing threats and in letting a learned fear fade over time. In rats and mice, the receptor (CB1) here clusters on the terminals of a group of nerve cells that act as a brake (they release GABA), and it eases this brake. Glass 1997Human tissuePhan 2008Human · clinical studyMarsicano 2002AnimalKatona 2001Animal
In mice without CB1, the fading of learned fear was clearly impaired; as fear faded, endocannabinoid levels in the amygdala rose. In rats, stress lowered anandamide in the amygdala, and this contributed to the size of the stress hormone response. There is a similar sign in humans: in healthy volunteers who occasionally used marijuana, THC reduced the amygdala's response to social cues signaling threat. Marsicano 2002AnimalHill 2009AnimalPhan 2008Human · clinical study
In humans, a common change (C385A) in the gene for the enzyme that breaks down anandamide (FAAH) leads to less of the enzyme being made. In healthy volunteers carrying this change, the amygdala's response to threatening faces was lower or faded faster, and their stress reactivity scores were lower; in mice carrying the same change, fear faded more easily. In healthy volunteers, blocking FAAH with a drug also strengthened recall of the fading (extinction) of a learned fear. However, a drug acting through the same pathway did not reduce symptoms more than placebo when added to internet-delivered therapy in people with PTSD. Hariri 2009Human · genetic studyGunduz-Cinar 2013Human · genetic studyAnimalDincheva 2015Human · genetic studyAnimalMayo 2020aHuman · clinical studyMayo 2025Human · clinical study
Student level: terms and cell types
[3H]CP55,940 autoradiography in human brain sections measured a high density of cannabinoid receptor binding in the amygdaloid complex (one step below the "very high" level in the hippocampal formation). The basolateral amygdala is a critical region for threat perception and for the extinction of fear memories. In rats and mice, CB1 is dense in the lateral and basal nuclei and absent from the central and medial nuclei; the receptor is presynaptic on the axon terminals of large, cholecystokinin (CCK)-positive GABAergic interneurons, and CB1 agonists shrink GABA-A–mediated IPSCs in principal cells. Glass 1997Human tissuePhan 2008Human · clinical studyMarsicano 2002AnimalKatona 2001Animal
In CB1−/− mice, short- and long-term extinction of auditory fear conditioning was clearly impaired, while learning and consolidation were unaffected; the CB1 antagonist SR141716A produced the same picture in wild-type mice. During extinction, endocannabinoid levels rose in the basolateral amygdala; long-term depression (LTD) of inhibitory currents there depended on endocannabinoids and CB1. In rats, restraint stress increased FAAH activity in the amygdala and lowered anandamide; inhibiting FAAH in the basolateral amygdala reduced the stress-induced rise in corticosterone, and this effect was abolished by the CB1 antagonist AM251. In humans, in a double-blind, crossover fMRI study, THC reduced amygdala reactivity to social cues signaling threat compared with placebo. Marsicano 2002AnimalHill 2009AnimalPhan 2008Human · clinical study
In carriers of FAAH C385A (rs324420) (385A), threat-related amygdala reactivity was lower (82 healthy volunteers), or amygdala habituation to threat was faster and stress-reactivity personality scores were lower; in knock-in mice carrying the same variant and in human carriers, fronto-amygdala connectivity was stronger, fear extinction was better and anxiety-like behavior was reduced. In mice, the FAAH inhibitor AM3506 increased anandamide in the basolateral amygdala and reduced fear after extinction; the effect was abolished by an intra-amygdala CB1 antagonist. In healthy volunteers, 10 days of PF-04457845 increased anandamide about 10-fold and strengthened extinction recall. In PTSD, 12 weeks of JNJ-42165279 (100 patients) raised anandamide but did not differ from placebo on the CAPS-5. Hariri 2009Human · genetic studyGunduz-Cinar 2013Human · genetic studyAnimalDincheva 2015Human · genetic studyAnimalMayo 2020aHuman · clinical studyMayo 2025Human · clinical study
Expert level: method notes and numbers
Amygdala: RNA level of the receptor gene in human tissue (tissue consensus data). In the HPA brain region data (amygdala), CB1 is 25.8 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 autoradiography with [3H]CP55,940, 11 human brains; the amygdaloid complex is in the "high" group together with the entorhinal cortex. Katona 2001: Wistar rats and mice (with CB1−/− controls), immunohistochemistry, electron microscopy, whole-cell recording; WIN 55,212-2 and CP 55,940 reduced evoked and spontaneous IPSCs and did not significantly change miniature IPSCs; they had no effect in the central nucleus or in CB1−/− mice. Glass 1997Human tissueKatona 2001Animal
Marsicano 2002: CB1−/− mice and wild-type mice given SR141716A; auditory fear conditioning, electrophysiology in basolateral amygdala slices and endocannabinoid measurement. Hill 2009: rats, 30-minute restraint stress, intra-amygdala microinjection; in stressed rats, amygdala anandamide was inversely related to serum corticosterone. Phan 2008: 16 healthy volunteers, double-blind crossover THC/placebo, fMRI; no effect in primary visual and motor cortex (dose not given in the abstract). Marsicano 2002AnimalHill 2009AnimalPhan 2008Human · clinical study
What is known about CBD?
In a randomized, double-blind, placebo-controlled brain imaging (fMRI) study in 15 healthy men, a single dose of CBD reduced the response of the amygdala and the cingulate cortex while participants looked at very fearful faces; this reduction was linked to a reduction in skin conductance fluctuations measured at the same time. This is a brain imaging finding in healthy volunteers, not a treatment result. Fusar-Poli 2009Human · 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.
Mixed results Weak evidence
In the guide: Social 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 | 13.3 | 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 | 0.2 | testis (4.4) |
| PPARγ PPARG | Gene switch · in the cell nucleus | 2.5 | adipose tissue (153.2) |
| 5-HT1A HTR1A | Serotonin receptor · in the cell membrane | 2.4 | hippocampal formation (6.1) |
| TRPV2 | Relative of TRPV1 · ion channel | 4.2 | lung (29.5) |
| Endocannabinoid enzymes | |||
| NAPE-PLD NAPEPLD | Makes anandamide | 1.7 | kidney (13.9) |
| FAAH | Breaks down anandamide | 16.9 | testis (46.0) |
| DAGLα DAGLA | Makes 2-AG | 3.6 | cerebral cortex (12.3) |
| DAGLβ DAGLB | Makes 2-AG | 6.1 | adrenal gland (15.2) |
| MGL MGLL | Breaks down 2-AG | 86.5 | adipose tissue (161.3) |
| ABHD6 | Breaks down 2-AG | 15.3 | liver (60.7) |
| ABHD12 | Breaks down 2-AG | 64.5 | 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
- Amygdala
- Amygdala · MeSH D000679 · UBERON 0001876 · Wikidata Q338924
- Receptors
- CB1 (CNR1, UniProt P21554) · CB2 (CNR2, UniProt P34972)
How to cite: cbd.school editorial team. Amygdala and the endocannabinoid system. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/amigdala/
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 13 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
- Phan KL, Angstadt M, Golden J et al. Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. J Neurosci. 2008;28(10):2313-9. PMID 18322078 · doi:10.1523/JNEUROSCI.5603-07.2008 Human · clinical study
- Marsicano G, Wotjak CT, Azad SC et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature. 2002;418(6897):530-4. PMID 12152079 · doi:10.1038/nature00839 Animal
- Katona I, Rancz EA, Acsady L et al. Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. J Neurosci. 2001;21(23):9506-18. PMID 11717385 · doi:10.1523/JNEUROSCI.21-23-09506.2001 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
- Hariri AR, Gorka A, Hyde LW et al. Divergent effects of genetic variation in endocannabinoid signaling on human threat- and reward-related brain function. Biol Psychiatry. 2009;66(1):9-16. PMID 19103437 · doi:10.1016/j.biopsych.2008.10.047 Human · genetic study
- Gunduz-Cinar O, MacPherson KP, Cinar R et al. Convergent translational evidence of a role for anandamide in amygdala-mediated fear extinction, threat processing and stress-reactivity. Mol Psychiatry. 2013;18(7):813-23. PMID 22688188 · doi:10.1038/mp.2012.72 Human · genetic studyAnimal
- Dincheva I, Drysdale AT, Hartley CA et al. FAAH genetic variation enhances fronto-amygdala function in mouse and human. Nat Commun. 2015;6:6395. PMID 25731744 · doi:10.1038/ncomms7395 Human · genetic studyAnimal
- Mayo LM, Asratian A, Lindé J et al. Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial. Biol Psychiatry. 2020;87(6):538-547. PMID 31590924 · doi:10.1016/j.biopsych.2019.07.034 Human · clinical study
- Mayo LM, Gauffin E, Petrie GN et al. The efficacy of elevating anandamide via inhibition of fatty acid amide hydrolase (FAAH) combined with internet-delivered cognitive behavioral therapy in the treatment of post-traumatic stress disorder: a randomized, placebo-controlled clinical trial. Neuropsychopharmacology. 2025;50(10):1564-1572. PMID 40382500 · doi:10.1038/s41386-025-02128-w Human · clinical study
- Fusar-Poli P, Crippa JA, Bhattacharyya S et al. Distinct effects of Δ9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry. 2009;66(1):95-105. PMID 19124693 · doi:10.1001/archgenpsychiatry.2008.519 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