Endocannabinoids are endogenous(Originating from within an organism, tissue, or cell.) substances known as ligands that activate cannabinoid receptors. Isolation and structure of a brain constituent that binds to the cannabinoid receptor.
Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R.
Science. 1992 Dec 18;258(5090):1946-9.
PMID: 1470919

The first endocannabinoid compound identified was N-arachidonoylethanolamide also known as Anandamide.

The second endocannabinoid identified was 2-arachidonoylglycerol ( 2-AG ). Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.
Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, et al.
Biochem Pharmacol. 1995 Jun 29;50(1):83-90.
PMID: 7605349

2-AG is a full agonist at both CB1 and CB2 receptors and it is present at much higher levels (170X) in the brain than Anandamide. A second endogenous cannabinoid that modulates long-term potentiation.
Stella N, Schweitzer P, Piomelli D.
Nature. 1997 Aug 21;388(6644):773-8.
PMID: 9285589

The third endocannabinoid identified was 2-arachidonyl-glyceryl ether ( noladin ether, 2-AGE ). 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor.
Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE, Kustanovich I, Mechoulam R.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3662-5. Epub 2001 Mar 20.
PMID: 11259648

It was found in the study referred to above, that 2-AGE binds to the CB1 cannabinoid receptor and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. Additionally, it was found to bind weakly to the CB2 receptor.

O-arachidonoyl-ethanolamine ( virhodamine ) is another endocannabinoid discovered. Virodhamine has been identified with antagonist properties at the CB1 cannabinoid receptor. Virodhamine is arachidonic acid and ethanolamine joined by an ester linkage. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor.
Porter AC, Sauer JM, Knierman MD, Becker GW, Berna MJ, Bao J, Nomikos GG, Carter P, Bymaster FP, Leese AB, Felder CC.
J Pharmacol Exp Ther. 2002 Jun;301(3):1020-4.
PMID: 12023533

The fifth identified endocannabinoid is N-arachidonoyl-dopamine ( NADA ). NADA is capable of activating CB1 receptors. NADA is an "endovanilloid". It also activates vanilloid VR1 receptors (coexpressed with cannabinoid CB1 receptors), which excites sensory nerves and causes release of sensory neurotransmitter. N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo.
Bisogno T, Melck D, Bobrov MYu, Gretskaya NM, Bezuglov VV, De Petrocellis L, Di Marzo V.
Biochem J. 2000 Nov 1;351 Pt 3:817-24.
PMID: 11042139

The sixth candidate for classification as an endocannabinoid is Lysophosphatidylinositol, (LPI). Recent evidence strongly suggests that GPR55 is a specific and functional receptor for LPI. Identification of GPR55 as a lysophosphatidylinositol receptor.
Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T.
Biochem Biophys Res Commun. 2007 Nov 3;362(4):928-34. Epub 2007 Aug 24.
PMID: 17765871

Endocannabinoids may play an important modulatory role in normal Blood Brain Barrier(BBB) physiology, and also afford protection to the BBB during ischaemic stroke, through a number of target sites. Endocannabinoids modulate human blood-brain barrier permeability in vitro.
Hind WH, Tufarelli C, Neophytou M, Anderson SI, England TJ, O'Sullivan SE.
Br J Pharmacol. 2015 Jun;172(12):3015-27. doi: 10.1111/bph.13106. Epub 2015 Apr 10.
PMID: 25651941

Further reading

IUPHAR/BPS: Endocannabinoid turnover
WikiPedia: Endocannabinoid systems
Medscape: Endocannabinoids

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