Mahgoub_2013_Eur.J.Pharmacol_720_310

The effects of cannabidiol (CBD), a non-psychoactive ingredient of cannabis plant, on the function of the cloned alpha7 subunit of the human nicotinic acetylcholine (alpha7 nACh) receptor expressed in Xenopus oocytes were tested using the two-electrode voltage-clamp technique. CBD reversibly inhibited ACh (100 muM)-induced currents with an IC50 value of 11.3 microM. Other phytocannabinoids such as cannabinol and Delta(9)-tetrahydrocannabinol did not affect ACh-induced currents. CBD inhibition was not altered by pertussis toxin treatment. In addition, CBD did not change GTP-gamma-S binding to the membranes of oocytes injected with alpha7 nACh receptor cRNA. The effect of CBD was not dependent on the membrane potential. CBD (10 microM) did not affect the activity of endogenous Ca(2+)-dependent Cl(-) channels, since the extent of inhibition by CBD was unaltered by intracellular injection of the Ca(2+) chelator BAPTA and perfusion with Ca(2+)-free bathing solution containing 2mM Ba(2+). Inhibition by CBD was not reversed by increasing ACh concentrations. Furthermore, specific binding of [(125)I] alpha-bungarotoxin was not inhibited by CBD (10 microM) in oocytes membranes. Using whole cell patch clamp technique in CA1 stratum radiatum interneurons of rat hippocampal slices, currents induced by choline, a selective-agonist of alpha7-receptor induced currents were also recoded. Bath application of CBD (10 microM) for 10 min caused a significant inhibition of choline induced currents. Finally, in hippocampal slices, [(3)H] norepinephrine release evoked by nicotine (30 microM) was also inhibited by 10 microM CBD. Our results indicate that CBD inhibits the function of the alpha7-nACh receptor.