In vivo pharmacology of endocannabinoids and their metabolic inhibitors: therapeutic implications in Parkinson's disease and abuse liability.
This review focuses on the behavioral pharmacology of endogenous cannabinoids (endocannabinoids) and indirect-acting cannabinoid agonists that elevate endocannabinoid tone by inhibiting the activity of metabolic enzymes. Similarities and differences between prototype cannabinoid agonists, endocannabinoids and inhibitors of endocannabinoid metabolism are discussed in the context of endocannabinoid pharmacokinetics in vivo. The distribution and function of cannabinoid and non-CB(1)/CB(2) receptors are also covered, with emphasis on their role in disorders characterized by dopamine dysfunction, such as drug abuse and Parkinson's disease. Finally, evidence is presented to suggest that FAAH inhibitors lack the abuse liability associated with CB(1) agonists, although they may modify the addictive properties of other drugs, such as alcohol.
Giuffrida
Andrea
A
Department of Pharmacology, University of Texas Health Science Center, San Antonio, TX 78229, USA. Giuffrida@uthscsa.edu
McMahon
Lance R
LR
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D063388:Endocannabinoids; D006801:Humans; D008024:Ligands; D010300:Parkinson Disease / Q000188:drug therapy*; D043882:Receptors, Cannabinoid / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism*
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D008024:Ligands; D043882:Receptors, Cannabinoid