Table 2.
Potency of pure cannabinoids and of most of their corresponding ‘botanical drug substance’ (BDS) as functional antagonists at TRPM8 channels
| Cannabinoid | IC50µM (against icilin 0.25 µM) |
|---|---|
| CBC | 40.7 ± 0.6 |
| CBC-BDS | 13.0 ± 1.1 |
| CBD | 0.06 ± 0.01 |
| CBD-BDS | 1.29 ± 0.04 |
| CBG | 0.16 ± 0.02 |
| CBG-BDS | 0.034 ± 0.003 |
| CBN | 0.21 ± 0.05 |
| CBDA | 4.78 ± 0.01 |
| CBDA-BDS | 1.2 ± 0.1 |
| CBGA | 1.31 ± 0.09 |
| CBDV | 0.90 ± 0.01 |
| CBDV-BDS | 1.2 ± 0.05 |
| CBGV | 1.71 ± 0.04 |
| CBGV-BDS | 0.95 ± 0.03 |
| THC | 0.16 ± 0.01a |
| THCA | 0.15 ± 0.02 |
| THCA-BDS | 0.056 ± 0.0026 |
| THCV | 0.87 ± 0.006 |
| THCV-BDS | 0.02 ± 0.006 |
| THCVA | 1.33 ± 0.019 |
| THCVA-BDS | 0.45 ± 0.057 |
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 TRPM8 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 5 min prior to icilin (0.25 µM). None of the compounds exerted any significant TRPM8-mediated effect on intracellular calcium per se (not shown).
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.