TABLE 1.

Overview of CBD molecular targets

Target	CBD Effect	Experiments/Results	References
CB1 receptor	Antagonist	CBD decreases THC and 2‐AG potencies in a GTPγS binding assay in mouse brain membranes	[22]
	Negative allosteric modulator	CBD allosterically reduces CB1 receptor signaling in HEK 293A cells	[21]
CB2 receptor	Antagonist	CBD decreases the potency of the receptor agonist, WIN55212, in a GTPγS assay with membranes from CHO cells overexpressing CB2 receptors	[22]
FAAH	Inhibitor	CBD inhibits [14C]‐AEA hydrolysis (IC50 < 100 µmol/L) in N18TG2 cell membrane preparations	[15]
GPR55	Antagonist	CBD decreases the potency of the agonist, CP55940, at nmol/L concentrations in a GTPγS assay with membranes from cells overexpressing GPR55	[82]
5‐HT1A	Agonist	CBD displaces [3H]8‐OH‐DPAT binding and increases G protein activity in CHO cells overexpressing the human 5‐HT1A receptor	[14]
	Anxiolytic‐like properties	CBD increases the distance travelled in an open field test in a mouse model of depression (OBX); this is blocked by a selective 5‐HT1A receptor antagonist, WAY100635. CBD increases sucrose consumption in the sucrose preference test, and glutamate release as assessed by microdialysis studies	[83]
	Analgesia	Reversal of CBD‐mediated analgesia by a selective 5‐HT1A receptor antagonist, WAY 100135, in a Von Frey filament test	[36]
Dopamine D2 receptor	Partial agonist	CBD inhibits radiolabeled domperidone binding to D2 receptors with dissociation constants of 11 nmol/L at dopamine D2High receptors and 2800 nmol/L at dopamine D2Low receptors in rat striatal membranes	[38]
Adenosine A1 receptor	Agonist	CBD induces antiarrhythmic effects against I/R‐induced arrhythmias in rats; this is blocked by the adenosine A1 receptor antagonist DPCPX	[45]
Adenosine A2A receptor	Agonist	Treatment with CBD (1 mg/kg) singinficantly reduces TNFα in mice challenged with LPS; this is blocked by pre‐treatment with the A2A adenosie receptor antagonist ZM 241385 (10 mg/kg, i.p.)	[43]
MOR and DOR	Allosteric modulator	CBD accelerates [3H]DAMGO dissociation from MOR and [3H]‐NTI from DOR induced by 10 μmol/L naloxone or 10 µmol/L naltrindole, respectively, in cerebral cortical tissue from male Wistar rats (assessed by kinetic binding studies)	[47]
TRPV1	Agonist	CBD increases cytosolic calcium levels to the same extent as the full agonist capsaicin in HEK 293 cells overexpressing the human TRVR1 receptor.	[15]
		CBD reduces leaver pressing in a cocaine self‐administration test; this is blunted by capsazepine, a TRPV1 receptor antagonist	[62]
Sodium channels	Inhibition	CBD inhibits hNav1.1‐1.7 currents (IC50 of 1.9–3.8 μmol/L). Voltage‐clamp electrophysiology in HEK‐293 cells and iPSC neurons shows that CBD preferentially stabilizes inactivated Nav channel states	[63]
Calcium channels	Inhibition of L‐type channels	Patch‐clamp techniques show that CBD inhibits L‐type Ca2+ channels (IC50 of 0.1 µmol/L) in rat myocytes.	[65]
	Bidirectional effect on Ca2+ levels	Mitochondrion‐specific Ca2+ sensor, Rhod‐FF, shows that CBD reduces [Ca2+]i levels under high excitability conditions but causes an increase under basal conditions in hippocampal primary neuronal cultures	[66]
PPARγ receptor	Agonist	CBD induces reactive gliosis in rat primary astroglial cultures; this is significantly blunted by a selective antagonist of PPARγ receptors, GW9662	[72]
	Anti‐inflammatory	CBD reduces leukocyte rolling and adhesion to the endothelium in a MIA‐injected model of inflammation in rats	[26]
	Antioxidant	CBD reduces hyperoxide toxicity in neurons stimulated with glutamate (evaluated by cyclic voltammetry and a fenton reaction‐based system); this is not altered by cannabinoid receptor antagonists	[12]