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Cannabinoid type-2 receptors modulate terpene induced anxiety-reduction in zebrafish

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dc.contributor.authorJohnson, Andréa L.
dc.contributor.authorVerbitsky, Ryan
dc.contributor.authorHudson, James
dc.contributor.authorDean, Rachel
dc.contributor.authorHamilton, Trevor
dc.date.accessioned2025-02-05T20:52:51Z
dc.date.available2025-02-05T20:52:51Z
dc.date.issued2023
dc.description.abstractTerpenes are the most extensive and varied group of naturally occurring compounds mostly found in plants, including cannabis, and have an array of potential therapeutic benefits for pathological conditions. The endocannabinoid system can potently modulate anxiety in humans, rodents, and zebrafish. The ‘entourage effect’ suggests terpenes may target cannabinoid CB1 and CB2 receptors, among others, but this requires further investigation. In this study we first tested for anxiety-altering effects of the predominant ‘Super-Class’ terpenes, bisabolol (0.001%, 0.0015%, and 0.002%) and terpinolene (TPL; 0.01%, 0.05%, and 0.1%), in zebrafish with the open field test. Bisabolol did not have an effect on zebrafish behaviour or locomotion. However, TPL caused a significant increase in time spent in the inner zone and decrease in time spent in the outer zone of the arena indicating an anxiolytic (anxiety decreasing) effect. Next, we assessed whether CB1 and CB2 receptor antagonists, rimonabant and AM630 (6-Iodopravadoline) respectively, could eliminate or reduce the anxiolytic effects of TPL (0.1%) and β-caryophyllene (BCP; 4%), another super-class terpene previously shown to be anxiolytic in zebrafish. Rimonabant and AM630 were administered prior to terpene exposure and compared to controls and fish exposed to only the terpenes. AM630, but not rimonabant, eliminated the anxiolytic effects of both BCP and TPL. AM630 modulated locomotion on its own, which was potentiated by terpenes. These findings suggest the behavioural effects of TPL and BCP on zebrafish anxiety-like behaviour are mediated by a selective preference for CB2 receptor sites. Furthermore, the CB2 pathways mediating the anxiolytic response are likely different from those altering locomotion.
dc.identifier.citationJohnson, A. L., Verbitsky, R., Hudson, J., Dean, R., & Hamilton, T. J. (2023). Cannabinoid type-2 receptors modulate terpene induced anxiety-reduction in zebrafish. Biomedicine & Pharmacotherapy, 168: 115760. https://doi.org/10.1016/j.biopha.2023.115760
dc.identifier.doihttps://doi.org/10.1016/j.biopha.2023.115760
dc.identifier.urihttps://hdl.handle.net/20.500.14078/3788
dc.language.isoen
dc.rightsAttribution-NonCommercial-NoDerivs (CC BY-NC-ND)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectendocannabinoid system
dc.subjectcannabis terpenes
dc.subjectzebrafish models
dc.subjectanxiety
dc.subjectCB 2 receptors
dc.subjectopen field test
dc.titleCannabinoid type-2 receptors modulate terpene induced anxiety-reduction in zebrafishen
dc.typeArticle

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