cannabidiol and cannabicyclol

Topics: Cannabidiol; Cannabis; Chromatography, Liquid; Dronabinol; Mass Spectrometry

The stimulation of prostaglandin E2 synthesis by delta 1-tetrahydrocannabinol in cultured cells is rapidly diminished by successive exposures to the drug at 24-hr intervals. Cannabidiol and cannabicyclol, two other constituents of cannabis, also displayed this in vitro tolerance effect. The phenomenon could, in addition, be observed by measuring the release of arachidonic acid from these cells, suggesting that the site of action of the cannabinoids is at one or more of the lipases that are believed to control prostaglandin synthesis under most conditions. Tolerance to cannabinoid action has been reported for a variety of in vivo parameters; thus, this in vitro system exhibits similar behavior and may, therefore, be a good model for studies on the molecular mechanisms involved in tetrahydrocannabinol action.

Topics: Arachidonic Acid; Arachidonic Acids; Calcimycin; Cannabidiol; Cannabinoids; Cell Line; Cell Survival; Cells, Cultured; Dinoprostone; Dronabinol; Drug Tolerance; Fibroblasts; Humans; Lung; Prostaglandins E; Time Factors

(-)-trans-delta 1-Tetrahydrocannabinol (delta 1-THC) antagonized the cyclic AMP responses of WI-38 fibroblasts to both prostaglandin E1 (PGE1) and catecholamines. Both cellular cyclic AMP accumulation and cyclic AMP escape to the incubation medium were reduced, but the reduction of escape was much more dramatic at all concentrations of the drug. Conversely, long term incubations of cells with delta 1-THC alone resulted in substantial accumulations of cyclic AMP in the incubation medium. This effect was potentiated by the phosphodiesterase inhibitor 1-methyl, 3-isobutylxanthine and appeared to result from weak agonist activity of the cannabinoid as determined by a) stimulation of radioactivity incorporated into cyclic AMP using 3H-adenine prelabelled cells, and b) a rapid and pronounced increase in the activity ratio of cellular protein kinase. The antagonistic effect of delta 1-THC on the cellular response to PGE1 was greater in preconfluent cells than in confluent monolayers. Further, the increased sensitivity of preconfluent cultures to delta 1-THC was associated with the appearance of cytoplasmic vacuoles in the perinuclear region of the cells. Cannabidiol acted similar to delta 1-Thc in affecting cyclic AMP metabolis whereas cannabinol and cannabicyclol showed mixed effects on the various parameters studied.

Topics: 1-Methyl-3-isobutylxanthine; Cannabidiol; Cannabinoids; Cells, Cultured; Contact Inhibition; Cyclic AMP; Dronabinol; Fibroblasts; Humans; Prostaglandins E