Cannabinoid systems

Piomelli D Giuffrida, A, Calignano, A and Rodriguez de Fonseca, F (2000) The endo-cannabinoid system as a target for therapeutic drugs. Trends Pharm. Sci. 21 218-224. 

In a study looking at oxygenated metabolites of AEA and their interaction with the cannabinoid system, a series of hydroxylated alkyl chains was prepared using different lipoxygenases as biocatalysts [152-154]. Of the seven AEA derivatives prepared, only the 5R-hydroxy (208), 125 -hydroxy (209) and 155 -hydroxy (210) derivatives had any affinity for the CBi receptor. Interestingly, the IdV-hydroxy compound (211) that was inactive at the CBi receptor displayed some affinity for the CB2 receptor [152] (see Table 6.18). 

All the aforementioned protein members of the cannabinoid system are large, membrane-bound proteins therefore, it is particularly difficult to obtain direct information about their tertiary structure. Thus, at the present time, structure-based drug design is not feasible. Detailed exploration of the SAR and subsequent ligand-based design are the most appropriate means for the development of molecular probes for these proteins. 

Consroe P. Brain cannabinoid systems as targets for the therapy of neurological disorders. Neurobiol Dis 1998 5 534—551. 

Marijuana and hashish are derivatives of the cannabis sativa plant 919 Cannabinoid effects in the CNS are mediated by the CB1 receptor 919 Endocannabinoids are endogenous ligands for the CB1 receptor 919 Endocannabinoids serve as retrograde messengers 920 There are many similarities between endogenous opioid and cannabinoid systems 921... 

Childers SR, Breivogel CS. (1998). Cannabis and endogenous cannabinoid systems. Drug Alcohol Dependence. 51(1-2) 173-87. 

Functional interactions between the nicotinic and cannabinoid systems have been proposed (Cohen et al. 2002) and several studies have tested the applicability of these ideas to nicotine discrimination. However cannabinoid agonists acting at cannabinoid CBi and CB2 receptors have failed to generalise with nicotine (Zaniewska et al. 2006). Results with the anandamide uptake and fatty acid amide hydrolase inhibitors AM-404 and URB 597, that elevate brain concentrations of endogenous cannabinoids, were also negative. Furthermore, neither the CBi receptor... 

Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgansberger W, Di Marzo V, Lutz B (2002) The endogenous cannabinoid system controls extinction of aversive memories. Natme 418 530-534 McKeman R, Rosdahl T, Reynolds D, Sur C, Wafford K, Atack J (2000) Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA-A receptor alpha-1 subtype receptors. Nat Neurosci 3 587-592... 

CS291 Rodriguez De Fonseca, F., M. A. Gorriti, A. Bilbao et al. Role of the endogenous cannabinoid system as a modulator of dopamine transmission implications for Parkinson s disease and schizophrenia. Neurotox Res 2001 3(1) 23-35. 

Endogenous cannabinoid system as a CS362 modulator of food intake. Int J Obes Relat Metab Disord 2003 27(3) ... 

Several lines of investigation indicate an interaction between the opioid and cannabinoid system (Welch and Eads, 1999). There is also evidence that a physiological stimulation of metabotrobic glutamate and NMDA receptors is required for cannabinoid-induced analgesia (Palazzo et al., 2001). 

Welch, S.P. and Eads, M. Synergistic interactions of endogenous opioids and cannabinoid systems, Brain Res. 1999, 848, 183-190. 

These smoked substances interact with the brain s own cannabinoid receptors to trigger dopamine release from the mesolimbic reward system. There are two known cannabinoid receptors, CB1 (in the brain, which is coupled via G proteins and modulates adenylate cyclase and ion channels) and CB2 (in the immune system). The CB1 receptors may mediate not only marijuana s reinforcing properties, but also those of alcohol. There is also an endogenous cannabinoid system (the brain s own marijuana) capable of activating these cannabinoid receptors functionally. These ert-docannabinoids are synthesized by neurons and inactivated by reuptake systems and enzymes in both neurons and glia. 

Similar to opioids, the cannabinoid system appears to be intricately involved in normal physiology, specifically in the control of movement, formation of memories, and appetite control. Basic research has discovered that members of this family of compounds have the capacity to protect threatened neurons, thereby slowing neurodegenerative processes that ultimately lead to physical disability. As the function of the physiological role of endocannabinoids becomes clearer, it appears the system may be involved in the pathology of several neurological diseases, specifically multiple sclerosis, spasticity, and pain. In 1999 the German journal, Forschende Komplementar-medizin und Klassische Naturheilkunde (Research in Complementary and Classical Natural Medicine) commented ... 

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