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Endocannabinoid system and mood disorders: priming a target for new therapies.
Pharmacol Ther 2013; 138(1):18-37P&T

Abstract

The endocannabinoid system (ECS), comprising two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana's psychoactive principle ∆(9)-tetrahydrocannabinol [∆(9)-THC]), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and the proteins for endocannabinoid biosynthesis and degradation, has been suggested as a pro-homeostatic and pleiotropic signaling system activated in a time- and tissue-specific way during physiopathological conditions. In the brain activation of this system modulates the release of excitatory and inhibitory neurotransmitters and of cytokines from glial cells. As such, the ECS is strongly involved in neuropsychiatric disorders, particularly in affective disturbances such as anxiety and depression. It has been proposed that synthetic molecules that inhibit endocannabinoid degradation can exploit the selectivity of endocannabinoid action, thus activating cannabinoid receptors only in those tissues where there is perturbed endocannabinoid turnover due to the disorder, and avoiding the potential side effects of direct CB1 and CB2 activation. However, the realization that endocannabinoids, and AEA in particular, also act at other molecular targets, and that these mediators can be deactivated by redundant pathways, has recently led to question the efficacy of such approach, thus opening the way to new multi-target therapeutic strategies, and to the use of non-psychotropic cannabinoids, such as cannabidiol (CBD), which act via several parallel mechanisms, including indirect interactions with the ECS. The state of the art of the possible therapeutic use of endocannabinoid deactivation inhibitors and phytocannabinoids in mood disorders is discussed in this review article.

Authors+Show Affiliations

CEITEC (Central European Institute of Technology) Masaryk University, Brno, Czech Republic. vincenzomicale@inwind.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23261685

Citation

Micale, Vincenzo, et al. "Endocannabinoid System and Mood Disorders: Priming a Target for New Therapies." Pharmacology & Therapeutics, vol. 138, no. 1, 2013, pp. 18-37.
Micale V, Di Marzo V, Sulcova A, et al. Endocannabinoid system and mood disorders: priming a target for new therapies. Pharmacol Ther. 2013;138(1):18-37.
Micale, V., Di Marzo, V., Sulcova, A., Wotjak, C. T., & Drago, F. (2013). Endocannabinoid system and mood disorders: priming a target for new therapies. Pharmacology & Therapeutics, 138(1), pp. 18-37. doi:10.1016/j.pharmthera.2012.12.002.
Micale V, et al. Endocannabinoid System and Mood Disorders: Priming a Target for New Therapies. Pharmacol Ther. 2013;138(1):18-37. PubMed PMID: 23261685.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endocannabinoid system and mood disorders: priming a target for new therapies. AU - Micale,Vincenzo, AU - Di Marzo,Vincenzo, AU - Sulcova,Alexandra, AU - Wotjak,Carsten T, AU - Drago,Filippo, Y1 - 2012/12/20/ PY - 2012/12/25/entrez PY - 2012/12/25/pubmed PY - 2013/8/27/medline SP - 18 EP - 37 JF - Pharmacology & therapeutics JO - Pharmacol. Ther. VL - 138 IS - 1 N2 - The endocannabinoid system (ECS), comprising two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana's psychoactive principle ∆(9)-tetrahydrocannabinol [∆(9)-THC]), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and the proteins for endocannabinoid biosynthesis and degradation, has been suggested as a pro-homeostatic and pleiotropic signaling system activated in a time- and tissue-specific way during physiopathological conditions. In the brain activation of this system modulates the release of excitatory and inhibitory neurotransmitters and of cytokines from glial cells. As such, the ECS is strongly involved in neuropsychiatric disorders, particularly in affective disturbances such as anxiety and depression. It has been proposed that synthetic molecules that inhibit endocannabinoid degradation can exploit the selectivity of endocannabinoid action, thus activating cannabinoid receptors only in those tissues where there is perturbed endocannabinoid turnover due to the disorder, and avoiding the potential side effects of direct CB1 and CB2 activation. However, the realization that endocannabinoids, and AEA in particular, also act at other molecular targets, and that these mediators can be deactivated by redundant pathways, has recently led to question the efficacy of such approach, thus opening the way to new multi-target therapeutic strategies, and to the use of non-psychotropic cannabinoids, such as cannabidiol (CBD), which act via several parallel mechanisms, including indirect interactions with the ECS. The state of the art of the possible therapeutic use of endocannabinoid deactivation inhibitors and phytocannabinoids in mood disorders is discussed in this review article. SN - 1879-016X UR - https://www.unboundmedicine.com/medline/citation/23261685/Endocannabinoid_system_and_mood_disorders:_priming_a_target_for_new_therapies_ DB - PRIME DP - Unbound Medicine ER -