Table 1.
Efficacy and potency of pure cannabinoids and of most of their corresponding ‘botanical drug substance’ (BDS) as functional agonists at TRPA1 channels, and the potency of pure cannabinoids as desensitizers of TRPA1 to the effect of allyl isothiocyanate
| Cannabinoid | Efficacy (% allyl isothiocyanate 100 µM) | Potency shown as EC50 (µM) | Desensitization (% allyl isothiocyanate 100 µM) IC50 (µM) |
|---|---|---|---|
| CBC | 119.4 ± 3.1 | 0.09 ± 0.01 | 0.37 ± 0.05 |
| CBC-BDS | 144.1 ± 6.0 | 0.25 ± 0.08 | NT |
| CBD | 115.9 ± 4.6 | 0.11 ± 0.05 | 0.16 ± 0.05 |
| CBD-BDS | 163.6 ± 11.9 | 0.38 ± 0.15 | NT |
| CBG | 99.9 ± 1.1 | 0.7 ± 0.03 | 13.0 ± 4.8 |
| CBG-BDS | No effect | ND | NT |
| CBN | 83.3 ± 4.0 | 0.18 ± 0.02 | 0.40 ± 0.04 |
| CBDA | 113.0 ± 11.0 | 5.3 ± 1.5 | 4.92 ± 0.09 |
| CBDA-BDS | 118.4 ± 11.9 | 1.0 ± 0.3 | NT |
| CBGA | 182.8 ± 0.2 | 8.4 ± 3.5 | 7.14 ± 0.17 |
| CBDV | 105.0 ± 0.7 | 0.42 ± 0.01 | 1.29 ± 0.38 |
| CBDV-BDS | 163.4 ± 28.3 | 0.5 ± 0.3 | NT |
| CBGV | 151.4 ± 0.9 | 1.6 ± 0.01 | 2.02 ± 0.25 |
| CBGV-BDS | 106.4 ± 4.0 | 0.8 ± 0.1 | NT |
| THC | 117 ± 12a | 0.23 ± 0.03a | NT |
| THCA | 41.6 ± 2.1 | 2.7 ± 0.9 | 95.25 ± 0.01 |
| THCA-BDS | 79.4 ± 2.0 | 0.22 ± 0.02 | NT |
| THCV | 243.0 ± 16.5 | 1.5 ± 0.6 | 3.07 ± 0.24 |
| THCV-BDS | 197.6 ± 7.9 | 0.07 ± 0.02 | NT |
| THCVA | 170.2 ± 15.9 | 16.4 ± 2.4 | 13.14 ± 0.85 |
| THCVA-BDS | 214.4 ± 20.6 | 5.8 ± 2.2 | NT |
| Allyl isothiocyanate | 100 | 1.4 ± 0.01 | 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 over-expressing the rat recombinant TRPA1 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 allyl isothiocyanate (100 µM), the effect of which was ∼30% of that of ionomycin (4 µM). In the antagonism-desensitization experiments, the same concentrations of the pure compounds were given to cells 5 min prior to allyl isothiocyanate (100 µM).
Data are from De Petrocellis et al. 2008.
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; NT, not tested.