2-arachidonoylglycerol (2-AG): weight gain and inflammation, and other undesirable properties

2-Arachidonoylglycerol (2-AG) is a metabolite belonging to the endocannabinoid family. 2-AG is related to palmitoylethanolamide, but seems to have opposite actions in a number if paradigms. It can be released if using ultramicronized PEA as has been described in a recent patent. Recently the endocannabinoid 2-arachidonoyl glycerol was added to cultured chick dorsal root ganglion neurons and this compound inhibited neurite elongation and induced growth cone collapse in a dose- and time-dependent manner. This gave rise to warnings in a recent article: “The Endocannabinoid, 2-Arachidonoyl Glycerol, Induces Growth Cone Collapse and Neurite Retraction in Growing Peripheral Sensory Neurons”.(World Journal of Neuroscience
Vol.05 No.01(2015), Article ID:53187). More of such findings can be identified.

In an animal model 2-AG increased weight gain and counteracted the anti-inflammatory properties of unsaturated fats such as EPA and DHA (Alvheim, 2012).

Such findings are especially of importance, since the ultramnicronzed formulation of palmitoylethanolamide (present in een PEA-houdend product sachets and Glialia, both Italian PEA formulations) increases this metabolite considerably, and we quote:

the administration per os of palmitoylethanolamide in the ultra-micronized form determinates a quick and huge increase of 2-AG in blood (which increase is higher than 400% compared to the basal levels).

Furthermore, in a recent animal model the inhibition of 2-AG biosynthesis appeared to be neuroprotective, possibly through the counteraction of the formation of pro-neuroinflammatory PGE2-G, formed from COX-2-mediated oxygenation of 2-AG (Valdeolivas 2013). 2-AG seems therefore a molecule with a Janus face. Last but not least, recent data showed that 2-AG can activate platelets. (Brantl, 2013), a function we might want not to enhance in certain patients.

Concentrations 2-AG after ultra-micronized PEA are 4 times increased

Concentrations 2-AG after ultra-micronized PEA are 4 times increased


Alvheim AR, Torstensen BE, Lin YH, Lillefosse HH, Lock EJ, Madsen L, Hibbeln JR, Malde MK. Dietary linoleic acid elevates endogenous 2-arachidonoylglycerol and anandamide in Atlantic salmon (Salmo salar L.) and mice, and induces weight gain and inflammation in mice. Br J Nutr. 2013 Apr 28;109(8):1508-17. doi: 10.1017/S0007114512003364. Epub 2012 Aug 10.

Valle Francesco Della, Gabriele Marcolongo, Valle Maria Federica Della. Composition containing ultra-micronized palmitoylethanolamide Patent WO 2011027373 A1

Valdeolivas S, Pazos MR, Bisogno T, Piscitelli F, Iannotti FA, Allarà M, Sagredo O, Di Marzo V, Fernández-Ruiz J. The inhibition of 2-arachidonoyl-glycerol (2-AG) biosynthesis, rather than enhancing striatal damage, protects striatal neurons from malonate-induced death: a potential role of cyclooxygenase-2-dependent metabolism of 2-AG. Cell Death Dis. 2013 Oct 17;4:e862. doi: 10.1038/cddis.2013.387.

Brantl SA, Khandoga AL, Siess W. Activation of platelets by the endocannabinoids 2-arachidonoylglycerol and virodhamine is mediated by their conversion to arachidonic acid and thromboxane A2, not by activation of cannabinoid receptors. Platelets. 2013 Oct 8.

Chizu Aso, Tomonori Takazawa, Tatsuo Horiuchi, Shigeru Saito The Endocannabinoid, 2-Arachidonoyl Glycerol, Induces Growth Cone Collapse and Neurite Retraction in Growing Peripheral Sensory Neurons. World Journal of Neuroscience Vol.5 No.1(2015), Paper ID 53187, 6 pages DOI:10.4236/wjns.2015.51001

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