Table 3.
Efficacy and potency of pure cannabinoids and of most of their corresponding ‘botanical drug substance’ (BDS) as functional agonists at TRPV1 channels, and the potency of pure cannabinoids as desensitizers of TRPV1 to the effect of capsaicin
| Cannabinoid | Efficacy (% ionomycin 4 µM) | Potency shown as EC50 (µM) | Desensitization (% capsaicin 0.1 µM) IC50 (µM) |
|---|---|---|---|
| CBC | <10 | 24.2 ± 3.1 | >50 |
| CBC-BDS | 29.1 ± 0.9 | 8.6 ± 1.2 | NT |
| CBD | 44.7 ± 0.02 | 1.0 ± 0.1 | 0.6 ± 0.05 |
| CBD-BDS | 59.9 ± 1.4 | 1.2 ± 0.4 | NT |
| CBG | 33.8 ± 2.3 | 1.3 ± 0.5 | 2.6 ± 0.2 |
| CBG-BDS | 23.0 ± 0.1 | 2.7 ± 0.1 | NT |
| CBN | <10 | 6.2 ± 3.7 | 81.7 ± 9.0 |
| CBDA | <10 | 19.7 ± 3.9 | 89.1 ± 0.3 |
| CBDA-BDS | 15.2 ± 0.01 | 10.3 ± 0.02 | NT |
| CBGA | 72.8 ± 2.0 | 21.0 ± 1.25 | 20.6 ± 0.5 |
| CBDV | 21.4 ± 0.6 | 3.6 ± 0.7 | 10.0 ± 0.5 |
| CBDV-BDS | 48.3 ± 1.1 | 4.5 ± 0.6 | NT |
| CBGV | 58.8 ± 0.9 | 2.0 ± 0.1 | 2.3 ± 0.3 |
| CBGV-BDS | 67.5 ± 1.8 | 3.9 ± 0.2 | NT |
| THC | <10 | ND | NT |
| THCA | <10 | ND | 19.2 ± 5.3 |
| THCA-BDS | <10 | 17.3 ± 0.1 | NT |
| THCV | 68.0 ± 1.6 | 1.5 ± 0.2 | 1.3 ± 0.1 |
| THCV-BDS | 48.9 ± 1.5 | 0.2 ± 0.04 | NT |
| THCVA | 20.0 ± 0.5 | 25.6 ± 1.1 | >50 |
| THCVA-BDS | 17.0 ± 1.4 | 29.0 ± 7.2 | NT |
The effect of the compounds on the elevation of intracellular calcium was measured by fluorescence as described in Methods and was assessed in HEK-293 cells stably overexpressing the human recombinant TRPV1 channel, and as a control, in wild-type HEK-293 cells. Data are means ± SEM of at least n = 3 separate experiments in which various concentrations (1, 10, 100, 1000, 10 000 and 25 000 nM) of the pure compounds, or amounts of BDS estimated to contain equimolar concentrations of the major cannabinoid, were given to cells. Efficacy was calculated as % of the effect obtained with ionomycin (4 µM). Capsaicin efficacy in this test is ∼75% of the effect of ionomycin. In the antagonism-desensitization experiments, the same concentrations of the pure compounds were given to cells 5 min prior to capsaicin (0.1 µM). CBC, cannabichromene; CBD, cannabidiol; CBDA, cannabidiol acid; CBDV, propyl analogue of CBD or cannabidivarin; CBG, cannabigerol; CBGV, cannabigivarin; CBN, cannabinol; THC, Δ9-tetrahydrocannabinol; THCA, THC acid; THCV, propyl analogue of THC or tetrahydrocannabivarin; THCVA, tetrahydrocannabivarin acid; ND, not determined; NT, not tested.