• cannabinoids;
  • nerve growth factor;
  • prostate;
  • Raf-1

Cannabinoids, the active components of marihuana, exert a variety of effects in humans. Many of these effects are mediated by binding to two types of cannabinoid receptor, CB1 and CB2. Although CB1 is located mainly in the central nervous system, it may also be found in peripheral tissues. Here, we study the effect of cannabinoids in the production of nerve growth factor by the prostate tumor cell line PC-3. We show that addition of Δ9-tetrahydrocannabinol to PC-3 cells stimulated nerve growth factor production in a dose-dependent and time-dependent manner. Maximal effect was observed at 0.1 µmΔ9-tetrahydrocannabinol and 72 h of treatment. Stimulation was reversed by the CB1 antagonists AM 251 and SR 1411716A. Pre-treatment of cells with pertussis toxin also prevented the effect promoted by Δ9-tetrahydrocannabinol. These results indicate that Δ9-tetrahydrocannabinol stimulation of nerve growth factor production in these cells was mediated by the cannabinoid CB1 receptor. The implication of Raf-1 activation in the mode of action of Δ9-tetrahydrocannabinol is also suggested.