Abstract
A1 and CB1 receptors are main targets for the cognitive effects of caffeine and Δ9-tetrahydrocannabinol (THC), two of the most heavily consumed psychoactive substances worldwide. Both receptors can coincide in the same neuronal structures and both couple to similar G proteins and transducing pathways. Ex vivo evidence revealed that A1 and CB1 receptors can interact, and recent in vivo studies showed that those interactions can influence the behavioral actions of cannabinoids. In particular, studies on interactions between the adenosine receptor nonselective antagonist caffeine and CB1 receptor agonists, such as THC, showed that these receptor interactions may have relevant consequences for the function of the hippocampus, which impact upon cognition. In addition, interactions between adenosine A2A receptors, also targeted by caffeine, and CB1 receptors may impact upon the motor and addictive actions of cannabinoids. Being so widely consumed, caffeine habits should therefore be taken into account whenever evaluating the influences of cannabinoids upon neuronal function or dysfunction in humans. Manipulation of the degree of activation of adenosine receptors with caffeine or adenosine receptor selective ligands should also be considered to reduce side effects of CB1 receptor ligands with therapeutic potential.
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