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CBD and GPR55

Long an "orphan" receptor · in the cell membrane.

Long an "orphan" 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 9GE3Last updated:

What's on this page?

Interactive 3D · real anatomy and real data

Where in your body are the cannabinoid receptors?

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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?

GPR55 is a membrane receptor identified from human genes in 1999 and long considered an "orphan" because no one knew which substance it worked with. In the first study, it was found in the caudate nucleus and putamen of the human brain. Today, its strongest candidate natural activator is lysophosphatidylinositol (LPI), a membrane lipid. Sawzdargo 1999Human tissueClaff 2025Molecular structure (lab)

Findings on CBD

In the first study, CBD showed activity at GPR55; most later studies, however, used CBD as a blocker here. CBD reduced the effect of GPR55 activators in human and mouse bone-resorbing cells; in rodent hippocampal slices, it abolished the effect of GPR55 activation on the synapse. CBD's role at this receptor is not fully clear. Ryberg 2007Cell / labWhyte 2009Cell / labAnimalSylantyev 2013AnimalRosenberg 2023Animal

Student level: experiments and numbers

Ryberg 2007: in cells transfected with human GPR55, CP55940 activated the receptor; cannabidiol and abnormal-cannabidiol, which are inactive at CB1/CB2, also showed activity at GPR55; GPR55 couples to Gα13 and can activate rhoA, cdc42 and rac1. Whyte 2009: the GPR55 agonists O-1602 and LPI increased osteoclast function; the effect was reduced in GPR55⁻/⁻ cells and by the GPR55 antagonist CBD. Sylantyev 2013: GPR55 activation transiently increased release probability at CA3–CA1 synapses; this was abolished when GPR55 was deleted or by CBD. Rosenberg 2023: in mice, the effects of LPI at excitatory and inhibitory synapses were abolished by CBD pretreatment. Ryberg 2007Cell / labWhyte 2009Cell / labAnimalSylantyev 2013AnimalRosenberg 2023Animal

Expert level: method notes

Method note

Ryberg 2007: no numerical EC50/IC50 for CBD in the abstract. Whyte 2009: in vitro osteoclast experiments, and histomorphometry and micro-CT in male GPR55⁻/⁻ mice. Sylantyev 2013: two-photon Ca²⁺ imaging and optical quantal analysis; dependent on presynaptic Ca²⁺ stores. Rosenberg 2023: GPR55 and LPI levels rose in acute PTZ seizures (animal model). Ibeas Bih 2015 lists GPR55 among the plausible targets. Ryberg 2007Cell / labWhyte 2009Cell / labAnimalSylantyev 2013AnimalRosenberg 2023AnimalIbeas Bih 2015Review

Structure: Human GPR55 with the G13 protein and the candidate natural activator LPI, cryo-EM 2.87 Å. The activator pocket opens toward the membrane. No CBD-bound structure exists. Claff 2025Molecular structure (lab)PDB 9GE3Molecular structure (lab) RCSB PDB 9GE3

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

Identifiers and citation

Protein
G protein-coupled receptor 55 (gene GPR55, human; UniProt Q9Y2T6)
Structure
RCSB PDB 9GE3: Human GPR55 with the G13 protein and the candidate natural activator LPI, cryo-EM 2.87 Å. The activator pocket opens toward the membrane. No CBD-bound structure exists.

How to cite: cbd.school editorial team. CBD and GPR55. Endocannabinoid system 3D map, cbd.school. Last updated October 24, 2026. https://cbd.school/learn/endocannabinoid-system-map/hedefler/gpr55/

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 8 references
  1. Sawzdargo M, Nguyen T, Lee DK et al. Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Brain Res Mol Brain Res. 1999;64(2):193-8. PMID 9931487 · doi:10.1016/s0169-328x(98)00277-0 Human tissue
  2. Claff T, Ebenhoch R, Kley JT et al. Structural basis for lipid-mediated activation of G protein-coupled receptor GPR55. Nat Commun. 2025;16(1):1973. PMID 40000629 · doi:10.1038/s41467-025-57204-y Molecular structure (lab)
  3. Ryberg E, Larsson N, Sjögren S et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007;152(7):1092-101. PMID 17876302 · doi:10.1038/sj.bjp.0707460 Cell / lab
  4. Whyte LS, Ryberg E, Sims NA et al. The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci U S A. 2009;106(38):16511-6. PMID 19805329 · doi:10.1073/pnas.0902743106 Cell / labAnimal
  5. Sylantyev S, Jensen TP, Ross RA, Rusakov DA. Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. Proc Natl Acad Sci U S A. 2013;110(13):5193-8. PMID 23472002 · doi:10.1073/pnas.1211204110 Animal
  6. Rosenberg EC, Chamberland S, Bazelot M et al. Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity. Neuron. 2023;111(8):1282-1300.e8. PMID 36787750 · doi:10.1016/j.neuron.2023.01.018 Animal
  7. 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
  8. RCSB Protein Data Bank, girdi 9GE3: Structure of GPR55 in complex with G13 and endogenous lipid agonist lysophosphatidylinositol (kriyo-EM, 2,87 Å). doi:10.2210/pdb9GE3/pdb. PDB verisi CC0 1.0. · doi:10.2210/pdb9GE3/pdb Molecular structure (lab)