Endocannabinoids are defined as endogenous agonists of cannabinoid receptors, that is, of the two G-protein-coupled receptors for the Cannabis psychoactive principle Δ9-tetra-hydrocannabinol. Two such endogenous mediators have been most thoroughly studied so far: anandamide and 2-arachidonoylglycerol. Here we review the mechanisms for the regulation of their levels under physiological and pathological conditions, and recent findings on their role in disease.
It is becoming increasingly clear that, although both anandamide and 2-arachidonoyl-glycerol are produced and degraded ‘on demand’, the levels of these two compounds appear to be regulated in different, and sometimes even opposing, ways, often using redundant molecular mechanisms. Alterations of endocannabinoid levels have been found in both animal models of pain, neurological and neurodegenerative states, gastrointestinal disorders and inflammatory conditions, and in blood, cerebrospinal fluid and bioptic samples from patients with various diseases.
Endocannabinoid levels appear to be transiently elevated as an adaptive reaction to re-establish normal homeostasis when this is acutely and pathologically perturbed. In some chronic conditions, however, this system also contributes to the progress or symptoms of the disorder. As a consequence, new therapeutic drugs are being designed from both stimulants and blockers of endocannabinoid action.
aEndocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli
bDepartment of Pharmaceutical Science, Università degli Studi di Salerno, Fisciano, Italy
Correspondence to Vincenzo Di Marzo, Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Comprensorio Olivetti, Fabbr. 70, 80078 Pozzuoli (NA), Italy Tel: +39 081 8041770; fax: +39 081 8041770; e-mail: firstname.lastname@example.org