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Handb Exp Pharmacol. 2005;(168):691-717.

Cannabinoid tolerance and dependence.

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Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980613, Richmond, VA 23298-0613, USA.


The use of marijuana for recreational and medicinal purposes has resulted in a large prevalence of chronic marijuana users. Consequences of chronic cannabinoid administration include profound behavioral tolerance and withdrawal symptoms upon drug cessation. A marijuana withdrawal syndrome is only recently gaining acceptance as being clinically significant. Similarly, laboratory animals exhibit both tolerance and dependence following chronic administration of cannabinoids. These animal models are being used to evaluate the high degree of plasticity that occurs at the molecular level in various brain regions following chronic cannabinoid exposure. In this review, we describe recent advances that have increased our understanding of the impact of chronic cannabinoid administration on cannabinoid receptors and their signal transduction pathways. Additionally, we discuss several potential pharmacotherapies that have been examined to treat marijuana dependence.

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