Signal Transduction of Peripheral Cannabinoid Receptor

Marijuana is one of the oldest drugs of abuse. Although its active ingredients have a long historyof use as therapeutic agents for a variety of maladies, its psychoactive actions limit its current use inWestern medicine. There is also evidence that immunosuppression results from chronic marijuana use.The central cannabinoid receptor from brain, and more recently, the peripheral cannabinoid receptor froma promyelocytic leukemic cell line, have been cloned. In Phase I stable cell lines expressing either thebrain or the peripheral receptor subtype will be established and will be used to develop a high throughputscreening program to screen for potent and selective agonists and antagonists. Macrophage cell linesand cell lines expressing either receptor subtype will also be used to study the signaling pathwaysemployed by the two receptors. The goal is to identify new therapeutic agents that would have thedesirable immunosuppressive and anti-inflammatory effects mediated by the peripheral cannabinoidreceptor, but devoid of central psychoactive effects.