The mode of action of cannabidiol is not fully understood and several mechanisms have been proposed:
(1) CBD acts as an antagonist at the central CB1 receptor and was able to inhibit several CB1 mediated THC effects (Zuardi et al. 1982). In a study by Petitet et al. (1998) CBD considerably reduced the receptor activation of a potent classical CB1 receptor agonist. CBD has a very low affinity for both known cannabinoid receptors. However, CBD antagonizes CB1 and CB2 receptor agonists at doses considerably lower than those of CBD needed to activate cannabis receptors (Pertwee et al. 2002). CBD was also shown to display inverse agonism at the human CB2 receptor, which may be a rational basis for its anti-inflammatory properties.
(2) CBD stimulates the vanilloid receptor type 1 (VR1) with a maximum effect similar in efficacy to that of capsaicin (Bisogno et al. 2001, Costa et al. 1998).
(3) CBD inhibits the uptake and hydrolysis of the endocannabinoid anandamide, thus increasing its concentration (Bisogno et al. 2001, Mechoulam et al. 2002).
(4) Researchers investigated the mechanisms, by which CBD reduces inflammatory and neuropathic pain in animals (Xiong et al. 2012). They found that the cannabinoid-induced analgesic effect is absent in mice lacking glycine receptors and concluded that this receptor mediates suppression of chronic pain.
(5) CBD binds to the equilibrative nucleoside-transporter-1, thus enhancing endogenous adenosine signaling. Some immunosuppressive effects may be based on this mechanism. The treatment of mice with a low dose of CBD is known to decrease tumor necrosis factor alpha (TNF-alpha) production (Malfait et al. 2000). This effect was reversed with an A2A adenosine-receptor antagonist.
(6) CBD displaces an agonist (8-hydroxy-2-di-n-protylamino-tetralin) from the 5-HT1A receptor in a concentration-dependent manner (Russo et al. 2005). CBD is a modest-affinity agonist at this receptor in humans.
(7) Cannabinoids, including CBD, are potent anti-oxidants. It was demonstrated that CBD prevents oxidative damage caused by H2O2 equally well or better than ascorbate (vitamin C) or tocopherol (vitamin E) (Hampson et al. 1998). CBD, when administered concurrently with high ethanol exposure in rats prevented neurodegeneration and this effect was attributed to its anti-oxidative effects (Hamelink et al. 2005).
(8) CBD binds to the GPR55 receptor, a putative cannabinoid receptor (Li et al. 2013). This effect is involved in the anti-inflammatory action of the cannabinoid.