Ingredient Reference
Anandamide (AEA): Chemistry, Receptors, Breakdown and What Supplements Contain
A reference on the endocannabinoid identified in 1992: how cells make and clear it, which receptors it binds, how it is measured, and what our label lists.
Shop AnandamideAnandamide on the Label
Exactly what is in our Anandamide Supplement, straight from the label.
How to use it (label directions): two capsules daily in the morning. Each bottle holds 30 servings. Related compounds: PEA and OEA are related compounds the body also makes, and they share anandamide's breakdown enzyme, FAAH. Use it as directed on the label.
Anandamide at a Glance
The core facts used to describe the molecule, each covered further down the page.
This page is a reference on the molecule itself. For research on its role in immune and inflammatory signaling, read The Anti-Inflammatory Power of Anandamide, Explained. For mood-focused anandamide supplements and what the research says about them, read Anandamide Supplements for Mood: What They Do and Whether They Work.
Structure, Class and the Name
Anandamide is a lipid: arachidonic acid, a 20-carbon omega-6 fatty acid with four double bonds, linked through an amide bond to ethanolamine. That places it in the N-acylethanolamine family with OEA and PEA, which carry different fatty acids on the same ethanolamine head. Being fat soluble, it moves through cell membranes rather than dissolving freely in water.
Devane, Hanus, Mechoulam and colleagues reported it in Science in December 1992 after screening pig brain for a natural compound that binds the cannabinoid receptor. They solved its structure with mass spectrometry and nuclear magnetic resonance, confirmed it by synthesis, and showed it competed with a labeled cannabinoid for receptor binding (Devane 1992). The name joins ananda, Sanskrit for bliss, to amide, the bond at its center.
It was the first endocannabinoid, one of the body's own cannabinoid receptor activators, to be found. A second, 2-arachidonoylglycerol (2-AG), was identified in canine gut in 1995 (Mechoulam 1995).
How Cells Make and Clear It: NAPE-PLD and FAAH
Unlike classic neurotransmitters, anandamide is not stored. Cells keep a precursor lipid in their membranes and convert it when stimulated, so the molecule exists mainly where and when it is made.
Step 1: Building the precursor
An N-acyltransferase enzyme attaches arachidonic acid to a membrane lipid, forming N-arachidonoyl phosphatidylethanolamine (NAPE).
Step 2: Release by NAPE-PLD
NAPE-hydrolyzing phospholipase D (NAPE-PLD) cuts NAPE to release anandamide. Okamoto and colleagues characterized it in 2004 and showed it also releases the other N-acylethanolamines, such as OEA and PEA (Okamoto 2004).
Step 3: Breakdown by FAAH
Fatty acid amide hydrolase (FAAH) splits anandamide into arachidonic acid and ethanolamine, ending its signal. Cravatt and colleagues purified and cloned it from rat liver membranes in 1996 (Cravatt 1996). A 2000 review lists anandamide, 2-AG and oleamide among its substrates and maps FAAH across organs and brain regions, where its pattern tracks cannabinoid receptors (Ueda 2000).
Why levels are local and short lived
Made on demand and cleared fast, anandamide rises and falls within specific tissues rather than circulating as a steady hormone. FAAH's control shows when the enzyme is removed: mice bred without it had 15-fold higher brain anandamide (Cravatt 2001).
CB1, CB2, TRPV1, PPARs and GPR55 Compared
Anandamide binds more than one kind of receptor. Each row names the target, what it is, and the type of evidence. Lab means cells, proteins or isolated tissue; animal means living animals.
Signaling in reverse at CB1
At brain synapses, anandamide often travels backward: the receiving neuron makes it, and it binds CB1 on the sending neuron, briefly lowering glutamate or GABA release. This feedback adjusts synaptic strength (Mackie 2006) and is part of the synaptic plasticity processes that keep circuits from running too hot.
Related Molecules: 2-AG, OEA and PEA
Three lipids that share building blocks or enzymes with anandamide but are not interchangeable with it.
2-AG
2-arachidonoylglycerol carries the same arachidonic acid tail on glycerol instead of ethanolamine, and binds CB1 and CB2. In rat brain neurons it is cleared mainly by monoglyceride lipase rather than FAAH (Dinh 2002).
OEA
Oleoylethanolamide pairs the ethanolamine head with oleic acid. In mice it acted through PPAR-alpha to increase satiety and did not bind cannabinoid receptors (Fu 2003). See our OEA ingredient guide and OEA supplement.
PEA
Palmitoylethanolamide pairs the ethanolamine head with palmitic acid, a saturated fat. Like OEA, it is released by NAPE-PLD (Okamoto 2004). Our PEA guide covers it in depth.
Anandamide, OEA and PEA are all ethanolamides cleared by FAAH. That shared enzyme is the link the label note above refers to.
How Researchers Measure Anandamide
Human studies measure anandamide in plasma or serum. Labs use liquid chromatography with tandem mass spectrometry (LC-MS/MS), often with an isotope-labeled internal standard.
Handling changes the number
Blood cells keep releasing anandamide after a sample is drawn. In blood from healthy volunteers, plasma anandamide in EDTA tubes held on ice for 60 minutes before centrifuging rose from about 1.3 to 2.8 micrograms per liter, and heparin tubes held at body temperature for 120 minutes reached about 11.9. Cell-free plasma did not rise, and the authors called for strictly standardized handling (Vogeser 2006).
What a blood level can and cannot tell you
A review of human studies describes blood anandamide as coming from several tissues, including brain, muscle, fat and blood cells. Time of day, recent exercise and recent meals shift it, and serum runs higher than plasma. The only animal study to compare blood and brain directly found them moving in opposite directions under chronic stress (Hillard 2018), so values are best compared within one study using the same tubes, timing and method.
Why a Label Lists Anandamide, and the Oral Route
Products built around anandamide list anandamide itself, related ethanolamides such as PEA and OEA that share its breakdown enzyme, or ingredients aimed at its building blocks or at FAAH. Our Anandamide Supplement combines the first two, as the label section above shows.
Anandamide is fat soluble. FAAH, the enzyme that clears it, is found in the liver and many other organs (Cravatt 1996; Ueda 2000), and blood cells both release and break it down (Hillard 2018).
For how people use these products and what studies have looked at, see Anandamide Supplements for Mood: What They Do and Whether They Work. Practical questions about our product are answered in the Anandamide Supplement FAQ.
Human Research Versus Lab and Animal Work
Most of what is known about anandamide's chemistry and targets comes from cells, tissue and animals. Human studies mostly measure natural levels or compare people with a gene variant that lowers FAAH.
For cell and animal work on immune signaling, see The Anti-Inflammatory Power of Anandamide, Explained.
Safety Notes and Interactions
Use the product as directed on the label: two capsules daily in the morning. Individual sensitivity varies.
Endocannabinoid signaling crosses many hormone and neurotransmitter systems, so interactions are possible with medications that affect mood, sleep, seizure threshold or the nervous system. When in doubt, bring the product label to a qualified clinician and ask about interactions and timing.
Talk with a healthcare professional before use if you are pregnant or breastfeeding, managing a neurological or psychiatric condition, or taking prescription medications, especially for mood, sleep, seizures or blood pressure.
US Regulatory Status
In the United States, our Anandamide Supplement is sold as a dietary supplement under the Dietary Supplement Health and Education Act of 1994. The FDA does not have the authority to approve dietary supplements before they are sold. Supplement companies are responsible for making sure their products are safe and that label claims are truthful and substantiated (FDA 2022).
Anandamide, PEA and OEA do not appear on the DEA's alphabetical list of federally controlled substances, checked in October 2026. Statements about supplements describe support for normal structure or function and carry the FDA disclaimer below.
Key Facts in Brief
Anandamide is a fatty acid amide made on demand by NAPE-PLD and cleared by FAAH. In lab studies it acts at CB1, CB2, TRPV1, PPARs and GPR55. Its relatives 2-AG, OEA and PEA share parts of that machinery.
Human research mostly measures natural blood levels, which shift with sample handling, time of day, exercise and meals. Our label lists anandamide alongside PEA and OEA.
Anandamide FAQ
What is anandamide?
Anandamide (AEA, N-arachidonoylethanolamine) is a fatty acid amide the body makes from arachidonic acid. It was the first endocannabinoid identified, reported from pig brain in 1992, and it binds the CB1 and CB2 cannabinoid receptors. The name was coined from ananda, Sanskrit for bliss.
How is anandamide different from THC and CBD?
THC is a plant compound that also activates CB1. CBD is a plant compound with little activity at CB1 or CB2. Anandamide differs from both because the body makes it on demand from membrane lipids and the enzyme FAAH clears it.
How is anandamide broken down?
Mainly by fatty acid amide hydrolase (FAAH), which splits it into arachidonic acid and ethanolamine. Mice bred without FAAH had about 15 times more anandamide in the brain. PEA and OEA are broken down by the same enzyme.
What is on the Synchronicity Health Anandamide Supplement label?
Per serving of 2 capsules: anandamide 600 mg, with PEA 150 mg, OEA 100 mg and L-theanine 100 mg, with ginger extract in vegan capsules. The label directions are two capsules daily in the morning, and each bottle holds 30 servings.
Can a blood test measure anandamide?
Research labs measure it in plasma or serum with mass spectrometry. Results depend on sample handling, because blood cells keep releasing anandamide after the draw, and a blood level is not a direct readout of brain levels.
Is anandamide a controlled substance in the US?
Anandamide, PEA and OEA do not appear on the DEA's alphabetical list of federally controlled substances, checked in October 2026. Our product is sold as a dietary supplement.
Who should talk to a clinician before taking an anandamide supplement?
Anyone who is pregnant or breastfeeding, managing a neurological or psychiatric condition, or taking prescription medications, especially for mood, sleep, seizures or blood pressure. Take the product label to that conversation and use it as directed.
More on Anandamide
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Related guides
Sources
- Devane WA, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 1992. PubMed 1470919
- Mechoulam R, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochemical Pharmacology, 1995. Publication record
- Cravatt BF, et al. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature, 1996. PubMed 8900284
- Zygmunt PM, et al. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature, 1999. DOI 10.1038/22761
- Ueda N, et al. The fatty acid amide hydrolase (FAAH). Chemistry and Physics of Lipids, 2000. PubMed 11106785
- Cravatt BF, et al. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. PNAS, 2001. PubMed 11470906
- Dinh TP, et al. Brain monoglyceride lipase participating in endocannabinoid inactivation. PNAS, 2002. PubMed 12136125
- Fu J, et al. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature, 2003. DOI 10.1038/nature01921
- Okamoto Y, et al. Molecular characterization of a phospholipase D generating anandamide and its congeners. Journal of Biological Chemistry, 2004. PubMed 14634025
- Mackie K. Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength. International Journal of Obesity, 2006. PubMed 16570100
- Vogeser M, et al. Release of anandamide from blood cells. Clinical Chemistry and Laboratory Medicine, 2006. DOI 10.1515/CCLM.2006.065
- Ryberg E, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. British Journal of Pharmacology, 2007. PubMed 17876302
- Sun Y, et al. Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism. British Journal of Pharmacology, 2007. DOI 10.1038/sj.bjp.0707478
- Dincheva I, et al. FAAH genetic variation enhances fronto-amygdala function in mouse and human. Nature Communications, 2015. PubMed 25731744
- O'Sullivan SE. An update on PPAR activation by cannabinoids. British Journal of Pharmacology, 2016. DOI 10.1111/bph.13497
- Hillard CJ. Circulating endocannabinoids: from whence do they come and where are they going? Neuropsychopharmacology, 2018. PubMed 28653665
- Mayo LM, et al. Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice. Molecular Psychiatry, 2018. PubMed 30120421
- Lu HC, et al. Review of the endocannabinoid system. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2021. PubMed 32980261
- Siebers M, et al. Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans. Psychoneuroendocrinology, 2021. PubMed 33582575
- US Food and Drug Administration. Dietary Supplements: How FDA Helps Keep You Safe. Fact sheet, 2022. FDA fact sheet
- US Drug Enforcement Administration, Diversion Control Division. Controlled Substances, Alphabetical Order. Checked October 2026. DEA list
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. If you are pregnant, nursing, managing a neurological or psychiatric condition, or taking prescription medication, consult a qualified healthcare professional before use.
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