Figure 3

Antagonistic effect of CBD on neural activity is enhanced when combined with sub-effective doses of THC. Zebrafish larvae were exposed to a series of CBD and THC concentrations by themselves or in combination, which are mostly sub-effective, or in the case of CBD, were minimally effective. (a) and (d), Exemplar CaMPARI activity heat maps show an additive effect (minimizing neural activity) when exposed to 2 µg/ml (d) of each CBD and THC compared to CBD or THC by themselves (as plotted in (e)). When 1 µg/ml of 1:1 CBD and THC was applied, ratios show no additive effect as illustrated by quantifications and statistics in (b). (c) and (f), Locomotor activity from the same well at 5 dpf shows a clear reduction when CBD and THC is combined at 2 µg/ml each, but reduction mediated by CBD alone is almost as low as when combined with THC suggesting that CBD is the main component affecting locomotor activity. R/G is indicated by the calibration bar. Green-dashed lines depict mean values for MS-222-anesthetized samples (from Fig. 1). Biological replicates are n = 15–25. *compared to vehicle control (equal amount of MeOH in all experiments); ^# compared to CBD plus THC. One symbol is p < 0.05; Two symbols is p < 0.01.