Table 2.

Possible mechanisms of CBD behaviour effects. Evidence from in vitro studies. CHO, Chinese hamster ovary cells.

biological system	mechanism	biological system	concentration range	references
endocannabinoid/endovanilloid related mechanisms	CB1 receptor antagonist	mouse brain membranes	4.9 µM (Ki)a	[32]
	CB2 receptor inverse agonist	CHO transfected cells	4.2 µM (Ki)b	[32]
	TRPV1 agonist	HEK-293 transfected cells	3.2 µM (EC50)	[33]
	FAAH/anandamide transporter inhibition	HEK-293 transfected cells, rat brain membranes	7.5–8.6/22 µM (IC50)	[33,34]
serotonin-related mechanisms	5-HT1A receptor agonist	CHO transfected cells	16 µM (increases receptor response by 67%)	[35]
	5-HT2A receptor agonist	CHO transfected cells	32 µM (IC50)	[35]
	5-HT3 receptor antagonist	Xenopus laevis oocytes	10–30 µM	[36]
	suppression of mitogen-induced IDO activity (decreasing tryptophan metabolism)	human blood cells	8.9 µM (IC50)	[37]
others	intracellular (Ca2+) increase	hippocampal cell cultures/hippocampal preparations	approximately 1 µM (effective concentration)	[38,39]
	allosteric modulation of µ and δ opioid receptors	cerebral cortex preparations	100 µM	[40]
	PPArγ receptors agonist	aorta preparations	5 µM (IC50)	[41]
	GPR55 antagonist	cell membranes of transfected cells	445 nM (IC50)	[42]
	blockade of adenosine uptake/indirect A2 agonist	microglia and macrophages cell cultures	less than 250 nM (Ki)/500 nM (effective concentration)	[43,44]
	TRPV2 agonist	HEK-293 transfected cells/rat dorsal root ganglia (DRG) sensory neurons	3.7 µM (EC50)	[45]
	TRPM8 antagonist	HEK-293 transfected cells/rat dorsal root ganglia (DRG) sensory neurons	80–140 nM(IC50)	[46]
	TRPA1 agonist	HEK-293 transfected cells/rat dorsal root ganglia (DRG) sensory neurons	96 nM(EC50)	[46]
	P38 MAPKinase inhibition	PC12 cells	10−6–10−4 M (effective concentrations)	[47]
	NF-κB activation	PC12 cells	10−6–10−4 M (effective concentrations)	[47]
	inhibition of mitochondrial superoxide production	vascular endotelial cells	4 µM (effective concentration)	[48]
	inhibition of inducible nitric oxide synthase (iNOS) expression	kidney	10 mg kg−1	[49]

^aCBD was able to antagonize the effects of the CB1 agonist CP55940-induced stimulation of [35S]GTPgS binding to mouse brain membranes at a much lower concentration (K_B = 79 nM) than the K_i for displacement of the CB1 ligand.

^bCBD acts as an inverse agonist with a lower concentration (K_B = 65 nM) than the K_i for displacement of the CB2 ligand.