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From the body

2-AGENoladin ether

The ether analogue of 2-AG, a nanomolar CB1 agonist; endogenous status debated, no human data.

Unscheduled
Level of detail

C₂₃H₄₀O₃

CAS 222723-55-9

Family
Endocannabinoid or related mediatorPutative
Molar mass
364.60 g/mol

Updated on

In plain terms

Noladin ether is a molecule very close to 2-AG, one of the cannabinoids the body makes itself. Its particularity is to be assembled with a stronger bond, which makes it markedly harder for enzymes to break down. It is not found in hemp, its actual presence in the mammalian brain is still debated, and no study has been carried out in human beings.

Receptors and activity

Target network

CB1AgonistKi = 21.2 nMradioligand displacement, brain membranes
  • Activates

The lower the cited value, the closer the target sits to 2-AGE: one ring per factor of 100. A target with no measured value stays on the edge.

Where these targets live

Where each target has been found in humans, according to the cited studies. The map shows the target, not an effect of 2-AGE.

Brain, side view
Body, front view
Blood

CB1CB1 found in 7 regions of the body

  1. Basal gangliadenseMost dense in basal ganglia outflow nuclei1
  2. CerebellumdenseVery dense in the cerebellum1
  3. HippocampusdenseVery high concentrations in the hippocampus2
  4. AmygdaladenseHigh concentrations in the amygdala2
  5. CortexpresentPresent throughout the neocortex2
  6. Adipose tissuepresentExpressed in adipose tissue3
  7. GutpresentColonic epithelium, smooth muscle and plexus4

Map sources

  1. Herkenham M et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A, 1990 (new tab)
  2. Glass M et al. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience, 1997 (new tab)
  3. Engeli S et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes, 2005 (new tab)
  4. Wright K et al. Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology, 2005 (new tab)

Cited values

  1. CB1AgonistKi = 21.2 nM61 out of 100

    Hanuš L. et al., PNAS 2001 (new tab) · radioligand displacement, brain membranes

  2. GPR55AgonistEC50 = 10 nM · human67 out of 100

    Ryberg E. et al., Br J Pharmacol 2007 (new tab) · [35S]GTPγS binding, membranes expressing GPR55

  3. CB2AgonistKi = 480 nM · human39 out of 100

    Shoemaker J.L. et al., JPET 2005 (new tab) · human CB2, full agonist in GTPγS; contradicted by Ryberg 2007, no activation up to 30 µM

  4. PPARαAgonistno measured value cited
Bar length follows the measured value (Ki, Kd, EC50 or IC50), on one scale shared by every entry, from 100 µM to 0.1 nM. A target with no cited value has no bar.

Pharmacology

Isolated from porcine brain in 2001, noladin ether is the ether analogue of 2-arachidonoylglycerol: the ester link of 2-AG is replaced by an ether bridge, which largely shields it from monoacylglycerol lipase and lengthens its tissue lifetime. It behaves as a nanomolar-affinity CB1 agonist, Ki 21.2 nM, and, according to Shoemaker et al. (2005), as a full agonist at human CB2 with a Ki of 480 nM; Ryberg et al. (2007), however, found no CB2 activation up to 30 µM, and the two results remain in conflict. It activates GPR55 with an EC50 near 10 nM. In rodents, systemic administration reproduces part of the cannabinoid tetrad. Two major reservations frame this profile. First, the endogenous status of the compound is unsettled: one team quantified it in rat brain (Fezza 2002), another detected it in none of five species tested (Oka 2003). Second, human data are entirely absent, no pharmacokinetic, efficacy or safety study having been published in humans. Noladin ether remains a laboratory pharmacological tool.

Key sources.

History

Source
Absent from cannabis: the molecule is not one of the phytocannabinoids and has never been reported in the plant. It was isolated from pig brain and proposed as an endogenous constituent of mammals, but this quality remains contested. One team quantified it in rat brain, with the highest levels in the thalamus and the hippocampus; another, using gas chromatography coupled to mass spectrometry and fluorimetric liquid chromatography, detected it in none of the five species examined, rat, mouse, hamster, guinea pig and pig. The quantities available today come from chemical synthesis and serve as a laboratory reagent.

Biosynthetic pathway

In vivo

The pathway of formation remains undetermined. Since the bond to glycerol is an ether and not an ester, the compound cannot arise from the acylation that produces 2-AG, and an origin from alkylglycerol-type ether lipids has been suggested without ever being demonstrated. The team that detected the molecule in rat brain already noted that it must be formed by a pathway different from that of 2-AG. The team that did not find it concludes that no mammalian biosynthesis is established, and the question has not been settled since.

Classification

Family, origin and source verification

Family

Endocannabinoid or related mediator › Putative

Verification

Every fact on this entry was checked against its primary sources on 20 October 2026.

Wikipedia (English)

2-Arachidonyl glyceryl ether (new tab)

Article paired by the molecule's structure (InChIKey), revision read on 19 October 2026. Read as a second opinion, never cited as a source.

References

  1. Hanuš L. et al., 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor, PNAS 2001 (new tab)PMID 11259648
  2. Oka S. et al., Ether-linked analogue of 2-arachidonoylglycerol (noladin ether) was not detected in the brains of various mammalian species, J Neurochem 2003 (new tab)PMID 12787057
  3. Shoemaker J.L. et al., The endocannabinoid noladin ether acts as a full agonist at human CB2 cannabinoid receptors, JPET 2005 (new tab)PMID 15901805
  4. Fezza F. et al., Noladin ether, a putative novel endocannabinoid: inactivation mechanisms and a sensitive method for its quantification in rat tissues, FEBS Lett 2002 (new tab)PMID 11904167
  5. Duncan M. et al., Noladin ether, a putative endocannabinoid, attenuates sensory neurotransmission in the rat isolated mesenteric arterial bed via a non-CB1/CB2 Gi/o linked receptor, Br J Pharmacol 2004 (new tab)PMID 15148262
  6. O'Sullivan S.E., Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors, Br J Pharmacol 2007 (new tab)PMID 17704824
  7. Ryberg E. et al., The orphan receptor GPR55 is a novel cannabinoid receptor, Br J Pharmacol 2007 (new tab)PMID 17876302
  8. Laine K. et al., Comparison of the enzymatic stability and intraocular pressure effects of 2-arachidonylglycerol and noladin ether, Invest Ophthalmol Vis Sci 2002 (new tab)PMID 12356827
  9. Juntunen J. et al., Synthesis, in vitro evaluation, and intraocular pressure effects of water-soluble prodrugs of endocannabinoid noladin ether, J Med Chem 2003 (new tab)PMID 14584958

Identifiers

Names

Common name
Noladin ether
IUPAC name
2-[(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoxy]propane-1,3-diol
Other names
2-AG ether · HU-310

Identifiers

Formula
C₂₃H₄₀O₃
CAS
222723-55-9
PubChem CID
6483057(new tab)
InChIKey
CUJUUWXZAQHCNC-DOFZRALJSA-N
SMILES
CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCCOC(CO)CO

Machine-readable entry (JSON)

LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.