Cannabinoid interactions with ion channels and receptors

Figures & data

Figure 1. Line drawing chemical structures of cannabidiol (CBD) and trans-Δ⁹-tetrahydrocannabinol (THC)

Table 1. Quantitative results of Cannabidiol’s membrane protein interactions by target, cell type, and IC50 or EC50. Missing IC50 values indicate that dose–response curves were not produced, but significant effects were demonstrated.

	Target	Cell type	IC50 (µM)
Channels	Nav1.1	HEK-293	2.0 ± 0.1 [20]
	Nav1.2	HEK-293	2.9 ± 0.1 [20]
		iPSCs	1.3 ± 0.1 [20]
	Nav1.3	HEK-293	3.3 ± 0.1 [20]
	Nav1.4	HEK-293	1.9 ± 0.1 [20]
	Nav1.5	HEK-293	3.8 ± 0.2 [20]
	Nav1.6	HEK-293	3.0 ± 0.1 [20]
	Nav1.7	HEK-293	2.9 ± 0.1 [20]
	NaChBac	HEK-293	1.5 ± 0.2 [20]
	Kv2.1	HEK-293	3.7 ± 0.8 [20]
	TRPM8	HEK-293	0.06 ± 0.01 [26]
	Cav3.1	HEK-293	0.813* [27]
	Cav3.2	HEK-293	0.776* [27]
	Cav3.3	HEK-293	3.63* [27]
	VDAC1	Planar lipid bilayer	–[18]
Transporters	Adenosine uptake via ENT1	EOC-20 microglia	0.12 [28]
	Thymidine uptake via ENT1	EOC-20 microglia	0.19 [28]
Receptors	GPR55	HEK-293	0.445 ± 0.067 [29]
	H5-HT1aR	CHO Cells	–[30]
	5-HT2aR	CHO Cells	–[30]
	Target	Cell Type	EC50 (µM)
Channels	TRPV1	HEK-293	1.0 ± 0.1[26]
	TRPV2	HEK-293	1.25 ± 0.23[26]
	TRPA1	HEK-293	0.11 ± 0.05[26]
Receptors	α1 homomers GlyRs	n/a	132.4 ± 12.3[25]
	α1β1 heteromers GlyRs	n/a	144.3 ± 22.7 [25]

^* Numbers calculated from pEC50 values

Ghovanloo M-R, Shuart NG, Mezeyova J, et al. Inhibitory effects of cannabidiol on voltage-dependent sodium currents Running title: CBD Inhibition of Nav Currents. doi:10.1074/jbc.RA118.004929

 Google Scholar

De Petrocellis L, Ligresti A, Moriello AS, et al. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011;163(7):1479–1494.

 PubMed Web of Science ®Google Scholar

Ross HR, Napier I, Connor M. Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol. J Biol Chem. 2008;283(23):16124–16134.

 PubMed Web of Science ®Google Scholar

Rimmerman N, Ben-Hail D, Porat Z, et al. Direct modulation of the outer mitochondrial membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: a novel mechanism for cannabinoid-induced cell death. Cell Death Dis. 2013;4(12):e949–e949.

 PubMed Web of Science ®Google Scholar

Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci U S A. 2006;103(20):7895–7900.

 PubMed Web of Science ®Google Scholar

Ryberg E, Larsson N, Sjögren S, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2009;152(7):1092–1101.

 Web of Science ®Google Scholar

Russo EB, Burnett A, Hall B, et al. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005;30(8):1037–1043.

 PubMed Web of Science ®Google Scholar

Ahrens J, Demir R, Leuwer M, et al. The nonpsychotropic cannabinoid cannabidiol modulates and directly activates Alpha-1 and Alpha-1-Beta glycine receptor function. Pharmacology. 2009;83(4):217–222.

 PubMed Web of Science ®Google Scholar