ArticlebioRxiv : the preprint server for biology2025
The pro-, but not anti-nociceptive effects of Cannabidiol depend on Trpa1b in larval Zebrafish.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The promiscuous ligand cannabidiol (CBD) shows promise as an analgesic, but its complex pharmacodynamics has made it difficult to identify its mechanism(s) of action. Numerous putative CBD receptors including cannabinoid receptors CB1 and CB2, as well as Trpv1 and Trpa1-the receptors for capsaicin and mustard-oil (AITC) respectively-have been proposed to contribute to CBD-mediated analgesia. Larval zebrafish have several attributes that lend themselves to inquiries into the biology of nociception. The neural circuits underlying nociception in zebrafish larvae are highly analogous to those found in higher vertebrates. Notably, the small size and optical clarity of zebrafish enable holistic evaluation of analgesic function utilizing behavioral and imaging platforms. Here we report that in larval zebrafish CBD serves both anti- and pro-nociceptive functions. Utilizing place aversion assays as a proxy for nociception, we found that low concentrations of CBD inhibit aversion to noxious chemical stimuli including AITC and acetic acid. Counterintuitively, we found that higher concentrations of CBD potentiated nocifensive behavior as measured by enhanced thermal aversion and increased locomotion. Knockdown of Trpa1b eliminated the algogenic effects of CBD while having no effect on its analgesic properties, as it abolished
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