TABLE 1.
Activity of compounds at hCB1R.
| Compound | [3H]CP55,940 | cAMP inhibition | βarrestin2 recruitment | |||
|---|---|---|---|---|---|---|
| Ki (nM) | Emin (%) | EC50 (nM) | Emax (%) | EC50 (nM) | Emax (%) | |
| CP55,940 | 13 (5.6—33) | 1.0 ± 4.7 | 1.0 (0.13—3.9) | 100 ± 6.2 | 910 (700—1,200) | 100 ± 3.3 |
| ∆9-THC | 35 (17—71) | 0.0 ± 3.5 | 5.2 (0.52—11) | 70 ± 7.7* | 600 (200—840) | 47 ± 7.8* |
| ∆8-THC | 360 (120—1,000)*# | 30 ± 5.0*# | 440 (76—620)*# | 56 ± 9.6*# | >10,000 | 21 ± 1.8*# |
| CBN | 140 (47—670)* | 71 ± 3.1*# | 49 (14 – 160)*# | 64 ± 4.6*# | >10,000 | 6.9 ± 0.96*# |
| ∆6a,10a-THC | 1,000 (470 – 2,000)*# | 1.7 ± 6.5 | 600 (260—1,300)*# | 100 ± 11# | >10,000 | 54 ± 4.9* |
| 11-OH-∆9-THC | 0.37 (0.10—1.3)*# | 70 ± 1.7*# | 11 (2.0—49) | 28 ± 3.9*# | >10,000 | 47 ± 9.4* |
| Curcumin | >10,000 | 100 ± 2.0*# | >10,000 | 6.2 ± 0.76*# | >10,000 | 8.9 ± 2.2*# |
| Egc G | >10,000 | 95 ± 3.4*# | >10,000 | 5.6 ± 0.52*# | >10,000 | 7.2 ± 0.85*# |
| Olivetol | 17 (3.3—90) | 57 ± 5.5*# | >10,000 | 5.6 ± 1.6*# | >10,000 | 8.3 ± 2.1*# |
| PEA | >10,000 | 46 ± 5.3*# | 730 (210—1,600)*# | 26 ± 1.8*# | 2,100 (920—3,100) | 5.6 ± 3.3*# |
| Piperine | >10,000 | 37 ± 2.8*# | >10,000 | 5.5 ± 0.63*# | >10,000 | 7.9 ± 0.97*# |
| Quercetin | 350 (44—860)* | 78 ± 8.1*# | >10,000 | 4.6 ± 0.80*# | >10,000 | 7.0 ± 1.2*# |
| ∆8-THC + ∆9-THC | 2.6 (0.46—6.5)*# | 7.0 ± 3.1 | 2.1 (0.58—12) | 54 ± 1.6*# | >10,000 | 8.7 ± 3.0*# |
| CBN + ∆9-THC | 170 (17—260) | 20 ± 5.4 | >10,000 | 60 ± 7.1* | >10,000 | 3.0 ± 0.21*# |
| ∆6a,10a-THC + ∆9-THC | 8.8 (0.29—14)# | 1.5 ± 4.1 | 7.7 (0.89—19) | 100 ± 4.4# | >10,000 | 56 ± 2.7* |
| 11-OH-∆9-THC + ∆9-THC | 1.2 (0.23—7.4)# | 5.1 ± 3.1 | 11 (2.0—29) | 23 ± 4.4*# | >10,000 | 44 ± 5.4* |
| Curcumin + ∆9-THC | >10,000 | 24 ± 6.8 | 3.1 (0.62—16) | 2.4 ± 5.0*# | >10,000 | 1.8 ± 0.27*# |
| Egc G + ∆9-THC | 7.9 (1.4—7.1)# | 3.0 ± 3.9 | 4.0 (0.88—18) | 13 ± 4.1*# | >10,000 | 2.5 ± 0.28*# |
| Olivetol + ∆9-THC | 4.6 (0.83—29) | 1.1 ± 2.7 | >10,000 | 61 ± 7.7* | >10,000 | 1.4 ± 0.31*# |
| PEA + ∆9-THC | >10,000 | 1.7 ± 2.1 | 57 (10—280) | 103 ± 4.8# | >10,000 | 14 ± 2.2*# |
| Piperine + ∆9-THC | >10,000 | 12 ± 7.2 | >10,000 | 48 ± 7.6*# | >10,000 | 1.7 ± 0.28*# |
| Quercetin + ∆9-THC | 350 (68—590) | 3.2 ± 8.1 | 19 (5.3—95) | 0.59 ± 4.3*# | >10,000 | 1.2 ± 0.44*# |
Compound activity was quantified for [3H]CP55,940 binding, inhibition of forskolin-stimulated cAMP, or βarrestin2 recruitment in CHO cells stably expressing hCB1R and treated with phytomolecules. Data were fit to a variable slope (four parameters) non-linear regression in GraphPad (v. 9.0). n ≥ 6 independent experiments were performed in triplicate. Emax and Emin refer to the top and bottom of the concentration–response curves, respectively. Data are expressed as nM with 95% CI or %CP55,940 response, mean ± SEM. *p < 0.05 compared to CP55,940; #p < 0.05 compared to ∆9-THC within assay and measurement as determined via non-overlapping 95% CI or one-way ANOVA followed by Tukey’s post hoc test.