Expression of Fatty Acid Amide Hydrolase (FAAH) in Human, Mouse, and Rat Urinary Bladder and Effects of FAAH Inhibition on Bladder Function in Awake Rats

Diuretic Effects of Cannabinoids

“…For example, anandamide may increase bladder contractility, especially in inflamed tissues; these effects are blocked by coadministration of capsazepine, indicating involvement of TRPV1 receptors (Dinis et al, 2004;Avelino and Cruz, 2006). On the other hand, increasing levels of anandamide after local administration of a fatty acid amide hydrolase inhibitor also lead to decreased contractility of normal bladder tissue-effects that are antagonized by CB1 and CB2 selective antagonists (Strittmatter et al, 2012). Such opposing actions have led to the suggestion that the net regulatory effects of anandamide on bladder function result from a balance of CB1, CB2, and TRPV1 effects (Dinis et al, 2004;Avelino and Cruz, 2006).…”

“…As with the effects of cannabis, both increases and decreases in urine loss have been reported with anandamide, and mechanisms through which these different effects are mediated appear to be complex. Endocannabinoids influence the release of urine through multiple mechanisms that may include vanilloid receptor type I (TRPV1) or cannabinoid CB1 and CB2 receptors, which are all found throughout the lower urinary tract (Avelino and Cruz, 2006;Tyagi et al, 2009;Strittmatter et al, 2012). For example, anandamide may increase bladder contractility, especially in inflamed tissues; these effects are blocked by coadministration of capsazepine, indicating involvement of TRPV1 receptors (Dinis et al, 2004;Avelino and Cruz, 2006).…”

Cannabinoids and the Urinary Bladder

“…These effects were prevented by a selective CB2 antagonist. Similarly, another FAAH inhibitor, URB597 has been found to have a functional role in the colon, where FAAH has been localized by reducing inflammation [77,82,83]. The use of a FAAH inhibitor needs to be explored further in the urinary bladder because it may be the way forward in treating OAB symptoms.…”

“…In addition, pharmacological targeting of the homeostasis of endogenous cannabinoids by manipulating the degradation enzymes, may also offer the possibility of avoiding the CNS side effects of exogenous cannabinoids. FAAH, an enzyme that specifically degrades anandamide has been localised in the urinary bladder [56,77,81]. Inhibition of FAAH activity with FAAH inhibitor Oleoyl Ethyl Amide (OEtA), significantly increased inter-contraction intervals, micturition volume, bladder capacity and threshold pressure urodynamic parameters in rats which reflect sensory functions of micturition.…”

“…In addition to using an intravesical route of administration for cannabinoid drugs in order to bypass the CNS effects associated with activation of CB1, the use of CB2 agonists and FAAH inhibitors is being explored and appear promising [76,77]. There is emerging evidence that activation of CB2 inhibits tissue inflammation and has analgesic properties [78][79][80].…”