. 2020 Aug 25;21(17):6115. doi: 10.3390/ijms21176115

Table 1.

Summary of the potencies (EC₅₀) (in nM) and efficacies (E_max)^* of synthetic cannabinoids (GCs) determined using cell assays.

Synthetic Cannabinoids	GTP Binding		cAMP		β-arrestin2		GIRK Channel		Cells	Assay	Ref.
Aminoalkylindoles Cyclohexylphenols	*EC₅₀*	*E_max* *(%)*	*EC₅₀*	*E_max* *(%)*	*EC₅₀*	E_max (%)	EC₅₀	E_max (%)
WIN 55,212-2	100	217							HEK293	[³⁵S]GTPγS	[46]
			32	65 ± 5^a					HEK293	GloSensor	[47]
			13	70 ± 4^b					HEK293	BRET	[48]
			5	64 ± 6^a					HEK293	GloSensor	[49]
			46	114 ± 5^c					HEK293	BRET	[50]
			47	113^c					HEK293	HitHunter	[51]
			7.6	92 ± 3^c	1288				HEK293	BRET	[52]
			14	107 ± 1^c	182	89 ± 2^c			CHO	Pathfinder	[53]
					570	59 ± 13			Neurons^d	BRET	[54]
							27	100^e	AtT20	MPSD	[55]
							282	100^e	AtT20	MPSD	[28]
							309	100^e	AtT20	MPSD	[56]
CP-55,940	17	163							HEK293	[³⁵S]GTPγS	[57]
	8	199^b	320	47 ± 8^a					HEK293	GloSensor	[47]
	0.4	95 ± 3							HEK293	[³⁵S]GTPγS	[46]
			0.3	100					CHO	HTRF	[58]
			8	58 ± 3^b					HEK293	BRET	[48]
			0.6	100	178	57 ± 3^c			HEK293	BRET	[52]
			0.2	100 ± 3^c	11	95 ± 2^c			CHO	Pathfinder	[53]
					138	49 ± 2^c			HEK293	BRET	[50]
					350	86 ± 4			Neurons^d	BRET	[54]
							23	100^c	AtT20	MPSD	[59]
							17	100^c	AtT20	MPSD	[60]
Naphtholylindoles	EC₅₀	E_max (%)	EC₅₀	E_max (%)	EC₅₀	E_max (%)	EC₅₀	E_max (%)
AM-1221	17	163^c							HEK293	[³⁵S]GTPγS	[57]
AM-2201					24	99^f			HEK293	NanoBiT	[61]
							37	111 ± 6^e	AtT20	MPSD	[28]
JWH-018	0.7	102 ± 10	1.7	90 ±	78	116 ± 16			CHO	³H-cAMP	[62]
					41	99^f			HEK293	NanoBiT	[61]
			16	64 ± 3					HEK293	BRET	[48]
					37	102^f			HEK293	NanoBiT	[63]
							18	116^b	AtT20	MPSD	[28]
JWH-122			3	102^c					CHO	HTRF	[58]
					72				HEK293	NanoLuc	[64]
N-(5-chloropentyl)					74	289^c			HEK293	NanoBiT	[61]
N-(5-bromopentyl)					284	261^c			HEK293	NanoBiT	[61]
N-(5-I=iodopentyl)					215	152^c			HEK293	NanoBiT	[61]
JWH-210	116	287							HEK293	[³⁵S]GTPγS	[57]
					25				HEK293	NanoLuc	[64]
			111	98^c					CHO	HTRF	[58]
Tetramethylcyclo-propyls	EC₅₀	E_max (%)	EC₅₀	E_max (%)	EC₅₀	E_max (%)	EC₅₀	E_max (%)
UR-144					426				HEK293	NanoLuc	[65]
Synthetic Cannabinoids	GTP Binding		cAMP		β-arrestin2		GIRK Channel		Cells	Assay	Ref.
Tetramethylcyclo-propyls cont.	EC₅₀	E_max (%)	EC₅₀	E_max (%)	EC₅₀	E_max (%)	EC₅₀	E_max (%)
UR-144							421	94 ± 4^e	AtT20	MPSD	[28]
XLR-11							98	110^e	AtT20	MPSD	[28]
			3981	65 ± 5^a					HEK293	GloSensor	[47]
			25	107 ± 2^c	389	88 ± 2^c			HEK293	BRET	[50]
			63	63 ± 2					HEK293	BRET	[48]
Indole & Indozole Carboxamides	EC₅₀	E_max (%)	EC₅₀	E_max (%)	EC₅₀	E_max	EC₅₀	E_max (%)
AB-CHMINACA	7.4	205							HEK293	[³⁵S]GTPγS	[66]
			0.28						CHO	HitHunter	[67]
			0.95	100 ± 4^c	30.9	110 ± 4			HEK293	BRET	[50]
			251	51 ± 2^b					HEK293	GloSensor	[47]
					3.45	390.5^f			HEK293	NanoBiT	[63]
							7.8	142^c	AtT20	MPSD	[60]
ADB-CHMINACA (MAB-CHMINACA)					.34	262.6^f			HEK293	NanoBiT	[63]
AB-PINACA	71	192							HEK293	[³⁵S]GTPγS	[66]
			79.4	69 ± 3^b					HEK293	GloSensor	[47]
					19	288^e			HEK293	NanoBit	[61]
							1.2	103 ± 4^e	AtT20	MPSD	[59]
							6.5	142 ± 15^c	AtT20	MPSD	[60]
5F-AB-PINACA	2.45	102 ± 7							HEK293	[³⁵S]GTPγS	[46]
					66	267^f			HEK293	NanoBiT	[61]
							0.48	94 ± 6^c	AtT20	MPSD	[59]
							2.8	132 ± 9^c	AtT20	MPSD	[60]
5F-ADB-PINACA							0.24	91 ± 7^c	AtT20	MPSD	[59]
					2.8	308^f			HEK293	NanoBiT	[63]
ADB-FUBICA							2.6	113 ± 8^c	AtT20	MPSD	[59]
					12.3	314^f			HEK293	NanoBiT	[61]
5F-CUMYL-PINACA			0.5	107 ± 6^c	16.9	97 ± 7			HEK293	BRET	[50]
AB-FUBINACA			0.79	116 ± 4^c	33	107 ± 4^c			HEK293	BRET	[50]
			1.36						CHO	³H-cAMP	[68]
					16	324^f			HEK293	NanoBiT	[61]
							1.8	108 ± 7^c	AtT20	MPSD	[59]
							2.1	151 ± 14^c	AtT20	MPSD	[60]
ABD-FUBINACA					0.69	339^f			HEK293	NanoBiT	[61]
							1.20	152 ± 11^c	AtT20	MPSD	[59]
5F-AMB-PINACA	1.3	96 ± 8^c							HEK293	[³⁵S]GTPγS	[46]
			0.6	98 ± 1^c	30	100 ± 2			HEK293	BRET	[50]
					15	259^f			HEK293	NanoBiT	[63]
							1.9	109 ± 3^c	AtT20	MPSD	[59]
5F-MDMB-PINACA	0.29	111 ± 9^c							HEK293	[³⁵S]GTPγS	[46]
					0.84	319^f			HEK293	NanoBiT	[63]
					1.78	331^f			HEK293	NanoBiT	[26]
MDMB-CHMICA			0.14						CHO	HitHunter	[67]
			0.7	117 ± 4^c	32	108 ± 1			HEK293	BRET	[50]
					1.77	285^f			HEK293	NanoBiT	[63]
AMB-CHMINACA					3.91	360^f			HEK293	NanoBiT	[63]
Synthetic Cannabinoids	GTP Binding		cAMP		β-arrestin2		GIRK Channel		Cells	Assay	Ref.
Indole & Indozole Carboxamides cont.	EC₅₀	E_max (%)	EC₅₀	E_max (%)	EC₅₀	E_max (%)	EC₅₀	E_max (%)
MDMB-CHMINACA					0.78	227^f			HEK293	NanoBiT	[63]
MDMB-FUBICA			1.0	108 ± 5^c	43	104 ± 2			HEK293	BRET	[50]
MDMB-FUBINACA	0.27	75							HEK293	[³⁵S]GTPγS	[46]
			0.65	216					CHO	LanceUltra	[69]
					0.36	241^f			HEK293	NanoBit	[63]
5F-MDMB-PICA			0.17	109 ± 7	20	111 ± 4			HEK293	BRET	[50]
			0.63	60 ± 4^b					HEK293	BRET	[48]

* - EC_50s were normalized as indicated by ^a-f (below); a – compared to 65% inhibition with WIN 55,212-2; b – percent of control measurements; c – maximal effect compared to CP55,940 (100%); d – striatal medium spiny projection neurons; e – maximal effect compared to WIN 55,212-2 (100%); f – maximal effect compared to JWH-018 (100%); BRET = bioluminescence resonance energy transfer; MPSD = membrane potential-sensitive dye; HTRF = homogeneous time-resolved fluorescence; NanoBiT = nanobinary technology assay; NanoLuc = nanoluciferase reporter assay.