Cellular approaches to the interaction between cannabinoid receptor ligands and nicotinic acetylcholine receptors

Cannabinoids are among the earliest known drugs to humanity. Cannabis plant contains various phytochemicals that bind to cannabinoid receptors. In addition, synthetic and endogenously produced cannabinoids (endocannabinoids) constitute other classes of cannabinoid receptor ligands. Although many pharmacological effects of these cannabinoids are mediated by the activation of cannabinoid receptors, recent studies indicate that cannabinoids also modulate the functions of various integral membrane proteins including ion channels, receptors, neurotransmitter transporters, and enzymes by mechanism(s) not involving the activation of known cannabinoid receptors. Currently, the mechanisms of these effects were not fully understood. However, it is likely that direct actions of cannabinoids are closely linked to their lipophilic structures. This report will focus on the actions of cannabinoids on nicotinic acetylcholine receptors and will examine the results of recent studies in this field. In addition some mechanistic approaches will be provided. The results discussed in this review indicate that, besides cannabinoid receptors, further molecular targets for cannabinoids exist and that these targets may represent important novel sites to alter neuronal excitability.