The effects of Cannabidiol (CBD), a non-psychoactive ingredient of cannabis plant, on the function of the cloned α₇ subunit of the human nicotinic acetylcholine (α₇ nACh) receptor expressed in Xenopus oocytes were tested using the two-electrode voltage-clamp technique. CBD reversibly inhibited ACh (100μM)-induced currents with an IC₅₀ value of 11.3µM. Other phytocannabinoids such as cannabinol and Δ⁹-tetrahydrocannabinol did not affect ACh-induced currents. CBD inhibition was not altered by pertussis toxin treatment. In addition, CBD did not change GTP-γ-S binding to the membranes of oocytes injected with α₇ nACh receptor cRNA. The effect of CBD was not dependent on the membrane potential. CBD (10µM) did not affect the activity of endogenous Ca²⁺-dependent Cl^– channels, since the extent of inhibition by CBD was unaltered by intracellular injection of the Ca²⁺ chelator BAPTA and perfusion with Ca²⁺-free bathing solution containing 2mM Ba²⁺. Inhibition by CBD was not reversed by increasing ACh concentrations. Furthermore, specific binding of [¹²⁵I] α-bungarotoxin was not inhibited by CBD (10µM) 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 α₇-receptor induced currents were also recoded. Bath application of CBD (10µM) for 10min caused a significant inhibition of choline induced currents. Finally, in hippocampal slices, [³H] norepinephrine release evoked by nicotine (30µM) was also inhibited by 10µM CBD. Our results indicate that CBD inhibits the function of the α₇– nACh receptor.
© 2013 Published by Elsevier B.V.

PMID:

 

24140434

 

[PubMed – as supplied by publisher]