The Endocannabinoid System

Although there are many yet umesolved issues concerning the life cycle of AEA and other endocannabinoids, it is clear that the endocannabinoid story is intimately associated with the lipid 

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In additon to the central role of endocannabinoids in the regulation of feeding behaviour, a peripheral role has also been described. Gomez and coworkers [360] reported that food deprivation produced a 7-fold reduction in (1) levels in the small intestine of rats, but not in the brain or stomach. Intestinal (1) levels returned to normal when feeding resumed. The authors also showed that peripheral, but not central administration of (382) reduced food intake. The endocannabinoid system has also been reported to regulate peripheral lipogenesis [361]. 

Furthermore, the presence of CB1 in the structures and pathways associated with the pathophysiology of Tourette s syndrome, and especially the functional link between CB1 and Di, D2, also argues that the endocannabinoid system may have some involvement in this disorder as well (Consroe, 1998). In addition, it has been suggested that activation of CB1 receptors, also owing to their link with the dopaminergic system, may reduce dyskinesia produced by L-DOPA in patients with Parkinson s disease (Brotsie, 1998). 

Several physiological roles of endocannabinoids have been identified, including memoiy, cognition, movement, and pain perception (Stella et al. 1997). Elucidation of the endocannabinoid systems is essential to the understanding of the effects of cannabis. There are both similarities and some pointed differences between the effects of exogenous and endogenous cannabinoids. 

Maldonado R, Valverde O, Berrendero F (2006) Involvement of the endocannabinoid system in drug addiction. Trends Neurosci 29 225-232... 

The endocannabinoid system might also be involved, since A9-tetrahydorcan-nabinol, the major active ingredient in cannabis, decreases somatically expressed withdrawal behaviors and the aversiveness of withdrawal in mecamylamine- and naloxone-precipitated nicotine abstinence (Balfour 2002). However, genetic knockout of the CBl cannabinoid receptors did not significantly affect somatically expressed withdrawal behaviors (Castane et al. 2002). 

Fambert DM, Fowler CJ. (2005) The endocannabinoid system Drug targets, lead compounds, and potential therapeutic applications. / Med Chem 48 5059-5087. 

Rather, they are both produced within neurons and released to flow backward across the synapse to find their receptors, designated as CBi and CBz. There are probably more of these CB receptors for marijuana in the human brain than for any other known neurotransmitter. The great abundance of these receptors and their widespread location gives an indication of importance of the endocannabinoid system in the regulation of the brain s normal functioning. 

Piomelli D, Giuffrida A, Calignano A and de Fonseca FR (2000) The endocannabinoid system as a target for therapeutic drugs. Trends in Pharmacological Sciences 21, 218-224. 

It is tempting to speculate that disinhibitory effects of endocannabinoids would promote learning, while endocannabinoid-mediated reductions in excitatory tran-mission underly amnestic effects. Thus, the role of the endocannabinoid system in learning and memory would depend on which synaptic inputs within a given brain region contain the receptor, and which inputs are activated during a given phase of... 

Katona I, Urban GM, Wallace M, Ledent C, Jung KM, Piomelli D, Mackie K, Freund TF (2006) Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci 26(21) 5628-37... 

The endocannabinoid system is constituted of various lipid species, which include precursors and metabolites of anandamide and 2-AG (Figs. 1 and 2). Each of these lipids appears to have functionally distinct biosynthetic pathways and... 

In recent years the rapid development of high-sensitivity analytical techniques such as mass spectrometry (MS) and liquid chromatography (LC) supported the investigation of the endocannabinoids as part of a complex lipid network. The identification of lipid components of the endocannabinoid system can be achieved in a single analytical step by state-of-the-art platforms such as tandem mass spectrometry (MS/MS), which provides the detailed structural information necessary for characterization of lipids and increases specificity in complex biological matrices. Furthermore, the implementation of ionization techniques such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) allow the coupling of LC to MS, and permits the separation and analysis of endocannabinoids with greater speed and accuracy. 

Dainese, E., Oddi, S., Bari, M., and Maccarrone, M. (2007). Modulation of the endocannabinoid system by lipid rafts. Curr. Med. Chem. 14, 2702-2715. 

Di Marzo, V. (2008). Targeting the endocannabinoid system To enhance or reduce Nat. Rev. Drug... 

THE ENDOCANNABINOID SYSTEM AS A TARGET FOR NOVEL ANXIOLYTIC AND ANTIDEPRESSANT DRUGS... 

Despite the significant advances made in recent years in the understanding of the neurobiology of the endocannabinoid system (Howlett et al., 2002 Piomelli,... 

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