Cannabidiol inhibits synaptic transmission in rat hippocampal cultures and slices via multiple receptor pathways

Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute slices. Experimental approach: The effect of CBD on synaptic transmission was examined in rat hippocampal cultures and acute slices using whole cell patch clamp and standard extracellular recordings respectively. Key results: CBD decreased synaptic activity in hippocampal cultures in a concentration-dependent and Pertussis toxin-sensitive manner. The effects of CBD in culture were significantly reduced in the presence of the cannabinoid CB1 receptor inverse agonist, LY320135 but were unaffected by the 5-HT1A receptor antagonist, WAY100135. In hippocampal slices, CBD inhibited basal synaptic transmission, an effect that was abolished by the proposed CB1 receptor antagonist, AM251, in addition to LY320135 and WAY100135. Conclusions and implications: CBD reduces synaptic transmission in hippocampal in vitro preparations and we propose a role for both 5-HT1A and CB1 receptors in these CBD-mediated effects. These data offer some mechanistic insights into the effects of CBD and emphasize that further investigations into the actions of CBD in the CNS are required in order to elucidate the full therapeutic potential of CBD.