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ABSTRACT
Administration of 9-tetrahydrocannabinol (THC) has been demonstrated to ameliorate the severity of withdrawal symptoms in rodents and humans. The purpose of the current investigation was to determine if upregulation of the endogenous cannabinoid anandamide would reduce the physical withdrawal signs in a mouse model of cannabinoid dependence. By blocking the primary enzyme responsible for anandamide degradation, fatty acid amide hydrolase (FAAH), the influence of elevated anandamide levels was examined on somatic signs of withdrawal in THC-dependent mice. While FAAH (—/—) mice showed similar withdrawal profiles to normal mice, acute administration of the FAAH inhibitor URB-597 significantly diminished the severity of withdrawal symptoms in wild type mice, but not in FAAH (—/—) mice. Unlike THC, repeated injections of high doses of URB-597 failed to lead to cannabinoid dependence. These findings suggest that FAAH inhibitors lack dependence liability, but FAAH may prove a promising therapeutic target to treat cannabis dependence.
Source: The FAAH inhibitor URB-597 ameliorates cannabinoid withdrawal in mice -- Schlosburg et al. 22 (1): 711.6 -- The FASEB Journal
Administration of 9-tetrahydrocannabinol (THC) has been demonstrated to ameliorate the severity of withdrawal symptoms in rodents and humans. The purpose of the current investigation was to determine if upregulation of the endogenous cannabinoid anandamide would reduce the physical withdrawal signs in a mouse model of cannabinoid dependence. By blocking the primary enzyme responsible for anandamide degradation, fatty acid amide hydrolase (FAAH), the influence of elevated anandamide levels was examined on somatic signs of withdrawal in THC-dependent mice. While FAAH (—/—) mice showed similar withdrawal profiles to normal mice, acute administration of the FAAH inhibitor URB-597 significantly diminished the severity of withdrawal symptoms in wild type mice, but not in FAAH (—/—) mice. Unlike THC, repeated injections of high doses of URB-597 failed to lead to cannabinoid dependence. These findings suggest that FAAH inhibitors lack dependence liability, but FAAH may prove a promising therapeutic target to treat cannabis dependence.
Source: The FAAH inhibitor URB-597 ameliorates cannabinoid withdrawal in mice -- Schlosburg et al. 22 (1): 711.6 -- The FASEB Journal
