Developmental effects of cannabidiol and Δ9-tetrahydrocannabinol in zebrafish.

Cannabidiol (CBD) has gained much attention in the past several years for its therapeutic potential in the treatment of drug-resistant epilepsy, such as Dravet Syndrome. While CBD has shown anecdotal efficacy in reducing seizure frequency, little is known regarding the potential adverse side-effects of CBD on physiology, development, organogenesis, or behavior. The goal of this project is to compare the relative morphological, behavioral, and gene expression phenotypes resulting after a developmental exposure to Δ9-tetrahydrocannabinol (THC) or CBD. Zebrafish were exposed from blastula through larval stage (96 hour post fertilization) to 0.3, 0.6, 1.25, 2.5, 5 mg/L (1, 2, 4, 8, 16 μM) THC or 0.07, 0.1, 0.3, 0.6, 1.25 mg/L CBD (0.25, 0.5, 1, 2, 4 μM). Despite the similarity in THC and CBD dysmorphologies, i.e., edemas, curved axis, eye/snout/jaw/trunk/fin deformities, swim bladder distention, and behavioral abnormalities, the LC50 for CBD (0.53 mg/L) was nearly seven times lower than THC (3.65 mg/L). At 96 hpf, c-fos, dazl, and vasa were differentially expressed following THC exposure, but only c-fos expression was significantly increased by CBD. CBD was more bioconcentrated compared to THC despite higher THC water concentrations. This work supports the potential for persistent developmental impacts of cannabinoid exposure, but more studies are needed to assess latent effects and their molecular mechanisms of toxicity.

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