Anandamide was the first identified endocannabinoid, named after the Sanskrit 'ananda' for inner bliss. Anandamide is produced from lipids in cellular membranes throughout the body. In the brain, Anandamide is primarily involved in negative feedback, keeping brain activity in balance. In the body, Anandamide is implicated in the suppression of tumour growth, pain and vomiting and the stimulation of eating.  

Chemical Name: 
IUPHAR entry: 
Wikipedia entry: 
Synthetic Pathways: 
Main pathways:

NAT: N-acyltransferase (Ca2+-dependent)

Produces NAPE from phospholipids.

iNAT: N-acyltransferase (Ca2+-independent)

Produces NAPE from phospholipids. Low abundant in brain.

NAPE-PLD: N-acyl-phosphatidylethanolamine (NAPE)-hydrolyzing phospholipase D

Produces Anandamide from NAPE

Additional pathways:

ABDH4: α/β-hydrolase 4

Lyso-PLD: lyso-phospholipase D

GDE1: glycerophosphodiester phosphodiesterase 1

PTPN22: protein tyrosine phosphatase, non-receptor type 22


Degradation Pathways: 

FAAH-1: fatty acid amide hydrolase-1

FAAH-2: fatty acid amide hydrolase-2

NAAA:  N-acylethanolamine-hydrolyzing acid amidase

LOXx: lipoxygenases

COX-2: cyclooxygenase-2

CytP450: cytochrome P450   


Less abundant in brain than 2AG, also found in the liver

Literature Discussion: 


In one study in rats, chronic stimulation of the endocannabinoid system (Anandamide) reduced addictive behavior (cocaine seeking), suggesting a role for the endocannabinoid system in suppressing Addiction (Chauvet et al., 2014).


2AG and AEA are involved in food intake regulation (Fride, Bregman, & Kirkham, 2005).


Hippocampal Anandamide, OEA and PEA were increased after social exposure (Kerr et al., 2013) once more stipulating the involvement of the endocannabinoid system in Autism.


Bone Cancer

CB2 agonists as Anandamide or THC affect the inflammatory process of bone cancer cells by modulating interleukin, tumor necrosis factor α and nuclear factor-κB expression and cofilin-1 protein (Hsu et al., 2007; Lu et al., 2015; Yang et al., 2015).

Cervical Cancer

cannabinoid receptors CB1CB2 and TRPV1 are expressed in the cervix. Anandamide bind to those receptors and has multiple functions on them (Ayakannu et al., 2015).

One of the effects of Anandamide (and THC) is to overexpress TIMP-1 with anti invasive and apoptotic functions on cancer cells (Ramer and Hinz, 2008).

However, the specific mechanism of the endocannabinoid system is not clear. Some studies suggest that Anandamide anti cancer properties depend on TRPV1 and not on CB1 or CB2 (Contassot et al., 2004; Ramer and Hinz, 2008).


In human patients, Anandamide was found to strongly inhibit bronchospasms and coughing (caused by chemical irritants) through activation of CB1 receptors (Calignano et al., 2000). 


In a rat study, Anandamide was found to induce bladder inflammation pain through TRPV1 suggesting this receptor might be a therapeutic target (Dinis et al., 2004). Interestingly, the opposite was found in another study where boosting Anandamide levels by preventing its breakdown exerted potent analgesic and anti-inflammatory effects (Wang et al., 2015). FAAH was responsible of breaking down Anandamide. Several studies found that CB2 was upregulated with Cystitis (Merriam et al., 2008; Tambaro et al., 2014) and that activation of CB2 with Anandamide or PEA attenuated pain and inflammation (Jaggar et al., 1998; Wang et al., 2013, 2014).


Anandamide levels (and to a lesser degree 2AG levels) and CB1 receptor availability are increased in the hippocampus (but not in the prefrontal cortex). Blocking the endocannabinoid system prevents the production of new neurons suggesting a role for cannabinoids in this process (Hill et al., 2010).


Anandamide and CB1CB2 and GPR55 receptors are implicated in the pathophysiology of Diabetes type 2 (Jenkin et al., 2014; Jourdan et al., 2014; Troy-Fioramonti et al., 2014).


In an experimental mouse model of Eczema endocannabinoids AEA and PEA were increased and TRPV1 and PPARα were upregulated (Petrosino et al., 2010). PEA enhances AEA activity at CB1CB2 and TRPV1 receptors and protects against keratinocyte inflammation in a TRPV1-, but not CB1CB2 or PPARα-dependent way.


Anandamide reduces burst-firing in neurons (Evans et al., 2008).

Functional Gastro-Intestinal Disorders

Patients with Crohn’s Disease have significantly reduced levels of Anandamide, but not 2AG or PEA, supporting a role for the endocannabinoid system in Crohn’s Disease (Di Sabatino et al., 2011). Intracerebrovascular application of Anandamide and 2AG appeared gastro-protective in ethanol-induced ulcers suggesting the involvement of endocannabinoids in the central nervous system (Gyires and Zádori, 2016).


Ayakannu, T., Taylor, A.H., Willets, J.M., and Konje, J.C. (2015). The evolving role of the endocannabinoid system in gynaecological cancer. Hum. Reprod. Update 21, 517–535.

Calignano, A., Kátona, I., Désarnaud, F., Giuffrida, A., La Rana, G., Mackie, K., Freund, T.F., and Piomelli, D. (2000). Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature 408, 96–101.

Chauvet, C., Nicolas, C., Thiriet, N., Lardeux, M.V., Duranti, A., and Solinas, M. (2014). Chronic Stimulation of the Tone of Endogenous Anandamide Reduces Cue- and Stress-Induced Relapse in Rats. Int. J. Neuropsychopharmacol. Off. Sci. J. Coll. Int. Neuropsychopharmacol. CINP.

Contassot, E., Tenan, M., Schnüriger, V., Pelte, M.-F., and Dietrich, P.-Y. (2004). Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1. Gynecol. Oncol. 93, 182–188.

Di Sabatino, A., Battista, N., Biancheri, P., Rapino, C., Rovedatti, L., Astarita, G., Vanoli, A., Dainese, E., Guerci, M., Piomelli, D., et al. (2011). The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease. Mucosal Immunol. 4, 574–583.

Dinis, P., Charrua, A., Avelino, A., Yaqoob, M., Bevan, S., Nagy, I., and Cruz, F. (2004). Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in Cystitis. J. Neurosci. Off. J. Soc. Neurosci. 24, 11253–11263.

Evans, R.M., Wease, K.N., MacDonald, C.J., Khairy, H.A., Ross, R.A., and Scott, R.H. (2008). Modulation of sensory neuron potassium conductances by Anandamide indicates roles for metabolites. Br. J. Pharmacol. 154, 480–492.

Fezza, F., Bari, M., Florio, R., Talamonti, E., Feole, M., & Maccarrone, M. (2014). Endocannabinoids, related compounds and their metabolic routes. Molecules (Basel, Switzerland), 19(11), 17078-17106.

Fride, E., Bregman, T., & Kirkham, T. C. (2005). Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood. Experimental Biology and Medicine (Maywood, N.J.)230(4), 225-234.

Gyires, K., and Zádori, Z.S. (2016). Role of cannabinoids in Gastrointestinal Mucosal Defense and Inflammation. Curr. Neuropharmacol. 14, 935–951.

Hill, M.N., Titterness, A.K., Morrish, A.C., Carrier, E.J., Lee, T.T.-Y., Gil-Mohapel, J., Gorzalka, B.B., Hillard, C.J., and Christie, B.R. (2010). Endogenous cannabinoid signaling is required for voluntary exercise-induced enhancement of progenitor cell proliferation in the hippocampus. Hippocampus 20, 513–523.

Hsu, S.-S., Huang, C.-J., Cheng, H.-H., Chou, C.-T., Lee, H.-Y., Wang, J.-L., Chen, I.-S., Liu, S.-I., Lu, Y.-C., Chang, H.-T., et al. (2007).Anandamide-induced Ca2+ elevation leading to p38 MAPK phosphorylation and subsequent cell death via apoptosis in human osteosarcoma cells. Toxicology 231, 21–29.

Jaggar, S.I., Hasnie, F.S., Sellaturay, S., and Rice, A.S. (1998). The anti-hyperalgesic actions of the cannabinoid Anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory painpain 76, 189–199.

Jenkin, K.A., McAinch, A.J., Zhang, Y., Kelly, D.J., and Hryciw, D.H. (2014). Elevated CB1 and GPR55 receptor expression in proximal tubule cells and whole kidney exposed to diabetic conditions. Clin. Exp. Pharmacol. Physiol.

Jourdan, T., Szanda, G., Rosenberg, A.Z., Tam, J., Earley, B.J., Godlewski, G., Cinar, R., Liu, Z., Liu, J., Ju, C., et al. (2014). Overactive cannabinoid 1 receptor in podocytes drives type 2 diabetic nephropathy. Proc. Natl. Acad. Sci. U. S. A. 111, E5420–E5428.

Kerr, D.M., Downey, L., Conboy, M., Finn, D.P., and Roche, M. (2013). Alterations in the endocannabinoid system in the rat valproic acid model of Autism. Behav. Brain Res. 249, 124–132.

Lu, C., Liu, Y., Sun, B., Sun, Y., Hou, B., Zhang, Y., Ma, Z., and Gu, X. (2015).Intrathecal Injection of JWH-015 Attenuates Bone cancerpain Via Time-Dependent Modification of Pro-inflammatory Cytokines Expression and Astrocytes Activity in Spinal Cord. Inflammation.

Merriam, F.V., Wang, Z., Guerios, S.D., and Bjorling, D.E. (2008). cannabinoid receptor 2 is increased in acutely and chronically inflamed bladder of rats. Neurosci. Lett. 445, 130–134

Pessina, F., Capasso, R., Borrelli, F., Aveta, T., Buono, L., Valacchi, G., Fiorenzani, P., Di Marzo, V., Orlando, P., and Izzo, A.A. (2014). Protective Effect of Palmitoylethanolamide in a Rat Model of Cystitis. J. Urol.

Petrosino, S., Cristino, L., Karsak, M., Gaffal, E., Ueda, N., Tüting, T., Bisogno, T., De Filippis, D., D’Amico, A., Saturnino, C., et al. (2010). Protective role of palmitoylethanolamide in contact allergic dermatitis. Allergy 65, 698–711.

Ramer, R., and Hinz, B. (2008). Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1. J. Natl. cancer Inst. 100, 59–69.

Tambaro, S., Casu, M.A., Mastinu, A., and Lazzari, P. (2014). Evaluation of selective cannabinoid CB(1) and CB(2) receptor agonists in a mouse model of lipopolysaccharide-induced interstitial Cystitis. Eur. J. Pharmacol. 729, 67–74.

Troy-Fioramonti, S., Demizieux, L., Gresti, J., Muller, T., Vergès, B., and Degrace, P. (2014). Acute Activation of cannabinoid Receptors by Anandamide Reduces Gastro-Intestinal Motility and Improves Postprandial Glycemia in Mice. Diabetes.

Wang, Z.-Y., Wang, P., and Bjorling, D.E. (2013). Activation of cannabinoid receptor 2 inhibits experimental Cystitis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 304, R846–R853.

Wang, Z.-Y., Wang, P., and Bjorling, D.E. (2014). Treatment with a cannabinoid receptor 2 agonist decreases severity of established Cystitis. J. Urol. 191, 1153–1158.

Wang, Z.-Y., Wang, P., Hillard, C.J., and Bjorling, D.E. (2015). Attenuation of Cystitis and pain sensation in mice lacking Fatty Acid amide hydrolase. J. Mol. Neurosci. MN 55, 968–976.

Yang, L., Li, F.-F., Han, Y.-C., Jia, B., and Ding, Y. (2015).cannabinoid receptor CB2 is involved in tetrahydrocannabinol-induced anti-inflammation against lipopolysaccharide in MG-63 cells. Mediators Inflamm. 2015, 362126.