Table 1.

CBD interaction with receptors and targets and their outcomes.

Receptor/Target	Action	Effect	Dose	Reference
CB1	Inverse agonist/negative allosteric modulator	Antidepressant-like effect.	10–60 nmol (in vivo); 0.01–5 µM	[67,68]
CB2	Inverse agonist/negative allosteric modulator	Anti-inflammatory effect.	<1 µM	[25,69]
TRPV1-4	Agonist	Nociceptor desensitization effect.	1–10 µM	[70,71]
TRPM8	Antagonist	Inhibition of [Ca2+] elevation induced by menthol and icilin.	<0.1 µM	[71,72]
TRPA1	Agonist	Regulation of TRPV1 function.	EC50 12 µM	[72]
5-HT1a receptors	Activation through direct, allosteric, or indirect effects	Associated with an antidepressant and anxiolytic effect.	50 mg/Kg (in vivo)	[73,74,75]
GPR55	Antagonist	Antagonization of proinflammatory effects.	10 mg/Kg (in vivo)	[76,77]
GPR3, GPR6 and GPR12	Inverse agonist	GPR3 is suggested as a biomarker for the prognosis of multiple sclerosis. GPR6 has been implicated in both HD and PD. GPR12 has been implicated in cell survival and neurite outgrow.	0.1–10 µM	[50,57]
PPAR-γ	Agonist/Up-regulator	Associated with anti-inflammatory and antioxidant properties through interaction with different transcription factors.	10 µM	[60,63,78]
TNF-α, IFN-β, IFN-γ, IL-1β, IL-17, IL-6	Modulator, decreases levels	Decrease in inflammation levels by targeting different pathways’ activity.	<20 µM	[79,80,81]
IL-4 and IL-10	Increases levels	Anti-inflammatory cytokines.	5 mg/Kg (in vivo)	[82,83]
ROS	Inhibitor	CBD inhibits a mechanism related to NADPH oxidase-mediated ROS production and NF-κB-dependent signaling events	<10 µM	[84,85]
iNOS and COX2	Inhibition of expression	Inhibition of the transcription of pro-inflammatory genes (i.e., iNOS, COX-2) contributing to CBD anti-inflammatory effect.	100 µM	[86,87]
Mitochondrial complexes I-IV	Inhibition	Decreases the activity of mitochondrial complexes (I, II, II-III, and IV).	50 µM	[88]
CaV3	Antagonist	Inhibition of the CaV3 channels might be involved in CBD analgesic effect.	1 µM	[89]
NaV	Inhibitor	Linked to antiseizure effects.	10 µM	[90]
VDAC1	Modulator	Associated to anticancer and immunosuppressive properties.	10 µM	[65]
AEA	Inhibitor	CBD acts in part by interfering with AEA inactivation and enhancing its inhibitory action on inflammation.	60 mg/Kg (in vivo)	[91,92]
FAAH	Inhibitor	Linked to CBD’s antipsychotic effect.	IC50 15 µM	[2,71]

Abbreviations: CB₁—cannabionoid receptor 1; CB₂—cannabinoid receptor 2; TRPV1-4—transient receptor potential cation channel subfamily V 1-4; TRPM8—transient receptor potential melastatin 8; TRPA1—Transient receptor potential cation channel subfamily A 1; 5-hydroxytryptamine (serotonin) receptor; EC50—half maximal effective concentration; GPR55—G protein-coupled receptor 55; GPR3—G protein-coupled receptor 3; GPR6—G protein-coupled receptor 6; GPR12—G protein-coupled receptor 12; HD—Huntington disease; PD—Parkinson disease; PPAR-γ—peroxisome proliferator-activated receptors gamma; TNF-α—tumor necrosis factor alpha; IFN-β—interferon beta; IFN-γ—interferon gamma; IL-1β—interleukin 1 beta; IL-17—interleukin 17; IL-6—interleukin 6; IL-4—interleukin 4; IL-10—interleukin 10; ROS—reactive oxygen species; CBD—cannabidiol; NADPH—Nicotinamide-adenine dinucleotide phosphate; iNOS—inducible nitric oxide synthase; COX-2—Cyclooxygenase 2; CaV3—T-type calcium channel 3; NaV—Voltage-gated sodium channel; VDAC1—voltage-dependent anion channel 1; AEA—anandamide; FAAH—fatty acid amide hydrolase; IC50—half maximal inhibitory concentration.