A COMPARISION OF DELTA-9-TETRAHYDROCANNABINOL DEPENDENCE IN C57Bl/6j MICE AND FATTY ACID AMIDE HYDROLASE KNOCK OUT MICE

• Main Author: Carlson, Brittany Leigh Alice
• Format: Others
• Published: VCU Scholars Compass 2007
• Subjects: marijuana; psychoactive; cannabinoid; THC withdrawal; physical dependence; G protein; Medical Pharmacology; Medical Sciences; Medicine and Health Sciences
• Online Access: http://scholarscompass.vcu.edu/etd/686; http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1685&context=etd

The idea that humans and laboratory animals can become physically dependent on marijuana or its primary psychoactive constituent, delta-9-tetrahydrocannabinol (THC), is gaining acceptance. However, there are no currently approved pharmacotherapies to treat cannabinoid withdrawal. The objective of this thesis was to evaluate whether elevating endogenous anandamide levels using mice lacking fatty acid amide hydrolase (FAAH), the enzyme responsible for anandamide metabolism, would ameliorate THC dependence. Mice were treated subchronically with a low or high THC dosing regimen and challenged with the CB1 receptor antagonist, rimonabant, to precipitate withdrawal. Following subchronic THC treatment, rimonabant precipitated a significant increase in paw flutters that was dependent on THC dose. However, FAAH-/- mice displayed a similar magnitude of withdrawal responses as wild type control mice, regardless of subchronic dosing regimen. Finally, rimonabant was equipotent in precipitating withdrawal responses in both genotypes. Collectively, these results demonstrate that FAAH-/- and +/+ mice show identical THC dependence, thus arguing against the notion that elevating anandamide levels through FAAH suppression will reduce cannabinoid withdrawal.