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Firstly, JWH-018 possesses a relatively high binding affinity (expressed as IC50 (occupation of 50% of the receptors)). Towards the cannabinoid receptor type. 1 (CB1) of 9.0 nM ± 5 and towards the cannabinoid receptor type 2 (CB2) of 2.94 nM ± 2.65 [9, 111, 112] compared to the binding affinities of delta-9 tetrahydrocannabinol (THC) of 40.7 nM ± 1.7 at the CB1 and 36.4 nM ± 10 at the CB2 receptor [24, 92].
Secondly, Chimalakonda et al. tested the biological effects by applying an in vitro [35S] guanosine-5’-O-(3-thio)- triphosphate ([35S]GTPγS). Binding assay and the compound showed full agonistic properties.
Moreover, JWH-018 induces inhibition of forskolin-stimulated cAMP accumulation in CHO cell lines expressing CB1 receptors with an EC50 14.7 ± 3.9, maximum inhibition 79%  and in Neuro2AWT cells with an EC50 of 5.31 ± 0.4 nM .
A pronounced difference with regard to THC is the formation of potential pharmacologically active JWH-018 metabolites.
), several JWH-018 metabolites retain high CB1 receptor binding affinity.
(relative rank of binding affinities: JWH-018 > JWH-018 N-(4-OH-pentyl) .> JWH-018 N-(5- OH-pentyl) > JWH-018 (5-OH-indole) = THC = JWH-018 (6-OH-indole) = JWH-018 N-(5-OH-pentyl) > JWH-073 N-(4-OH-butyl)) >> JWH-018 pentanoic acid [15, 16, 21]).
Furthermore, full agonistic binding has been shown for JWH-018, JWH-018 (5- OH-indole), JWH-018 (6-OH-indole) as well as for JWH-018 N-(5-OH-pentyl).
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imilar to the retention of CB1 receptor affinity, metabolites of JWH-018 also bind with high affinity at the CB2 receptor (relative rank of binding affinity: JWH-018 > JWH073 > THC > JWH-073-N (3-OH-butyl) > JWH-018 N-(5-OH-pentyl).
> JWH-018 (6- OH-indole) > JWH-018 N-(4-OH-pentyl). JWH-073 N-(4-OH-butyl) > JWH-073 (6- OH indole) >> JWH-018 pentanoic acid and JWH-073 butanoic acid).
Utilizing a [35S]GTPγS binding assay and an adenylyl cyclase assay to measure intrinsic activity. JWH-018 showed full agonist activity at CB2 receptors.
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