Cannabis receptor subtypes

It clearly appears that if the endocannabinoid system really plays a role in the physiopathology of schizophrenia, the activation of CBj receptors does not seem to be a crucial point. Interestingly, CBi is not the sole CB receptor subtype expressed in the brain. Some studies using CB, KO mice supported the existence of G-protein-coupled non-CBj and non-CBj cannabinoid receptors, sensitive to endocannabinoids, synthetic agonists, and rimonabant (Di Marzo et al., 2000 Breivogel et al., 2001 Pride et al., 2003). In addition, anandamide has been found to activate both CB, and vanilloid VR, receptors (for review see Di Marzo et al., 2002). However, the localizations and functions of such types of receptors are unclear, and their putative role in schizophrenia remains to be demonstrated. Although cannabis use appears to be neither a sufficient nor a necessary cause for psychosis, the current status of research on cannabis-associated psychosis (Leweke et al., 2004) is inconclusive, and further research is needed to understand the mechanisms by which cannabis is associated with psychosis. 

Two subtypes of G protein-coupled receptors for cannabis s psychotropic component, A -tetrahydrocannabinol (THC), have been cloned to date, the cannabinoid CBi and CB2 receptors (Howlett et al. 2004). Yet, five different types of endogenous agonists for these cannabinoid receptors have been identified so far (Fig. 1). These compounds, named endocannabinoids by analogy with THC (Di Marzo and Fontana 1995), are all derived from long-chain polyunsaturated fatty acids. In particular (1) the anandamides are amides of ethanolamine with polyunsaturated fatty acids with at least 20 carbon atoms and three 1,4-diene double bonds. The C20 4 homologue in this series, V-arachidonoylethanolamine (AEA) (Devane et al. 1992), also known simply as anandamide, has been most studied. 

Dronabinol (delta-9-tetrahydrocannabinol marinol) is a naturally occurring cannabinoid that can be synthesized chemically or extracted from the marijuana plant. Cannabis sativa. The antiemetic action of dronabinol probably relates to stimulation of the CBj subtype of cannabinoid receptors on neurons in and around the vomiting center. 

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