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CBD and 5-HT1A

Serotonin receptor · in the cell membrane.

Serotonin receptor · in the cell membrane. Where this target is found in the body, lab findings on CBD, the strength of evidence and the molecular structure, with sources.

CBD's other targetsStructure: PDB 7E2YLast 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.

Level
Reproductive organs

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.

Where is it, and what does it do?

5-HT1A is one of the receptors that serotonin binds to. It sits in the cell membrane; when serotonin binds, it switches on a G protein that slows the cell down (inhibits it). In the human brain, it is densest in the hippocampus, the raphe nuclei and the cerebral cortex. Hall 1997Human tissue

Findings on CBD

In the lab, CBD bound to and activated the receptor in cells engineered to carry the human 5-HT1A receptor; the authors called it "a modest affinity agonist". In membranes prepared from human brain tissue, however, the interaction was very weak: no effect was seen up to 10 µM, and at 100 µM the receptor's spontaneous activity decreased. In rats, some behavioral effects of CBD disappeared with a substance that blocks 5-HT1A. Russo 2005Cell / labMartínez-Aguirre 2020Human tissueResstel 2009Animal

Student level: experiments and numbers

Russo 2005: in CHO cells carrying cloned human 5-HT1A, CBD displaced the agonist [3H]8-OH-DPAT in a concentration-dependent manner (THC did not in the same range), increased [35S]GTPγS binding as serotonin does, and lowered cAMP. Martínez-Aguirre 2020: hippocampal and temporal neocortex membranes from autopsy and epilepsy surgery samples; pKi 4.29–4.74; between 1 pM and 10 µM, [35S]GTPγS did not change; at 100 µM, constitutive Gi/o activity fell by 24–40%, and WAY-100635 partly reversed this (inverse agonist at high concentration). In a rat model of acute stress, WAY100635 blocked the effect of CBD. Russo 2005Cell / labMartínez-Aguirre 2020Human tissueResstel 2009Animal

Expert level: method notes

Method note

Russo 2005: no numerical Ki or EC50 in the abstract; CBD less active at cloned rat 5-HT2A. Martínez-Aguirre 2020: n = 11 autopsy, n = 11 drug-resistant mesial temporal lobe epilepsy; no MeSH terms in PubMed, evidence type taken from the methods. A pKi of 4.3–4.7 corresponds roughly to a Ki of 20–50 µM (our conversion). Russo 2005Cell / labMartínez-Aguirre 2020Human tissue

Animal: Resstel 2009 (Wistar rats, acute restraint stress; WAY100635 blocked the effect of CBD on the cardiovascular and anxiety-like response). Rock 2012 (rats and Suncus murinus; indirect agonism via 5-HT1A autoreceptors in the dorsal raphe). No such blocking experiment was found in humans. Hall 1997: postmortem human brain, [3H]WAY-100635 autoradiography. Resstel 2009AnimalRock 2012AnimalHall 1997Human tissue

Structure: Serotonin-bound 5-HT1A–Gi complex, cryo-EM 3.0 Å. No CBD-bound structure exists. The receptor is fused to a bacterial protein (BRIL) to stabilize the structure. Xu 2021Molecular structure (lab)PDB 7E2YMolecular structure (lab) RCSB PDB 7E2Y

How lab concentrations compare with the level measured in blood, and CBD's other targets: CBD's other targets.

Identifiers and citation

Protein
5-hydroxytryptamine receptor 1A (gene HTR1A, human; UniProt P08908)
Structure
RCSB PDB 7E2Y: Serotonin-bound 5-HT1A–Gi complex, cryo-EM 3.0 Å. No CBD-bound structure exists. The receptor is fused to a bacterial protein (BRIL) to stabilize the structure.

How to cite: cbd.school editorial team. CBD and 5-HT1A. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/hedefler/5ht1a/

Protein structure from RCSB PDB (CC0 1.0). 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
  1. Hall H, Lundkvist C, Halldin C et al. Autoradiographic localization of 5-HT1A receptors in the post-mortem human brain using [3H]WAY-100635 and [11C]WAY-100635. Brain Res. 1997;745(1-2):96-108. PMID 9037397 · doi:10.1016/s0006-8993(96)01131-6 Human tissue
  2. Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005;30(8):1037-43. PMID 16258853 · doi:10.1007/s11064-005-6978-1 Cell / lab
  3. Martínez-Aguirre C, Carmona-Cruz F, Velasco AL et al. Cannabidiol Acts at 5-HT1A Receptors in the Human Brain: Relevance for Treating Temporal Lobe Epilepsy. Front Behav Neurosci. 2020;14:611278. PMID 33384591 · doi:10.3389/fnbeh.2020.611278 Human tissue
  4. Resstel LB, Tavares RF, Lisboa SF et al. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br J Pharmacol. 2009;156(1):181-8. PMID 19133999 · doi:10.1111/j.1476-5381.2008.00046.x Animal
  5. Rock EM, Bolognini D, Limebeer CL et al. Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT1A somatodendritic autoreceptors in the dorsal raphe nucleus. Br J Pharmacol. 2012;165(8):2620-34. PMID 21827451 · doi:10.1111/j.1476-5381.2011.01621.x Animal
  6. Xu P, Huang S, Zhang H et al. Structural insights into the lipid and ligand regulation of serotonin receptors. Nature. 2021;592(7854):469-473. PMID 33762731 · doi:10.1038/s41586-021-03376-8 Molecular structure (lab)
  7. RCSB Protein Data Bank, entry 7E2Y: Serotonin-bound serotonin 1A (5-HT1A) receptor-Gi protein complex (cryo-EM, 3.0 Å; bound SRO = serotonin, J40 = phosphatidylinositol derivative, CLR = cholesterol). doi:10.2210/pdb7E2Y/pdb. PDB data CC0 1.0. · doi:10.2210/pdb7E2Y/pdb Molecular structure (lab)