Blocking cannabinoid receptors affects zebrafish development, study shows

Disrupting natural cannabinoid receptors has a detrimental effect on the development of zebrafish, according to new research by University of Alberta biologists.

The study examines the endocannabinoid system, a natural system within both humans and zebrafish that regulates many of the body's functions--including the nervous, immune, and digestive systems--using neurotransmitters. The system also plays a major role in the body's development. It is also the system that is affected by cannabis consumption. In order to better understand the role of the endocannabinoid system, a topic of increasing interest with the legalization of cannabis in Canada, the researchers designed an experiment to better understand the role the natural, undisturbed system plays in development.

"We asked, if we block cannabinoid receptors during early development, do the zebrafish develop normally?" asked Declan Ali, professor in the Department of Biological Sciences and co-author on the study. "We saw various developmental changes when the endocannabinoid receptors in zebrafish were blocked. The changes are not major on their own, but when we consider the combined effects, we begin to see some more significant implications."

The results showed several negative outcomes for developing zebrafish, including reduced innervation of muscle fibres during motor neuron development. And preliminary research results suggest that implications were equally bad for fish that grew to be adults, who may have more physical deficits and behavioural abnormalities.

"Disturbing that system early on has long-term negative effects," said Ali, who is also associate dean (research) in the Faculty of Science. "We also looked at locomotion to see if their activity level was also affected by blocking the endocannabinoid system. We saw significant decreases in the level of locomotor activity in those fish whose endocannabinoid systems were blocked."

This research builds on Ali's 2018 research examining the developmental effects of exposing embryos to cannabis. "This fits with what we've been looking at so far. When we disturb the endocannabinoid system, whether by blocking it as in this study or by stimulating it through cannabis, disruption produces these deficits," explained Ali.

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The paper, "CB1 and CB2 receptors play differential roles in early zebrafish locomotor development," was published in the Journal of Experimental Biology (doi: 10.1242/jeb.206680).