The endocannabinoid system in zebrafish and its potential to study the effects of Cannabis in humans

Abstract

Zebrafish is considered an unprecedented animal model in drug discovery. A review of the literature presents highlights and elucidates the biological effects of chemical components found in Cannabis sativa. Particular attention is paid to endocannabinoid system (eCB) and its main receptors (CB1 and CB2). The zebrafish model is a promising one for the study of cannabinoids because of the many similarities to the human system. Despite the recent advances on the eCB system, there is still the need to elucidate some of the interactions and, thus, the zebrafish model can be used for that purpose as it respects the 3Rs concept and reduced time and costs. In view of the relevance of cannabinoids in the treatment and prevention of diseases, as well as the importance of the zebrafish animal model in elucidating the biological effects of new drugs, the aim of this study was to bring to light information on the use of the zebrafish animal model in testing C. sativa-based medicines.

C. elegans as a test system to study relevant compounds that contribute to the specific health-related effects of different cannabis varieties

“…Potential test models to study entourage effects of cannabis extracts like zebrafish embryo’s and C. elegans are already used as an essential tool in the pharmaceutical research industry to identify novel drugs and drug targets, and to study the molecular mechanisms behind the mode of action of drugs or complex herbal mixtures. The endocannabinoid system including the CB1 and CB2 receptors are present in zebrafish; and recently, the zebrafish model system was successfully applied to study the health-promoting effects of cannabinoids as compared to cannabis extracts (Nixon et al 2021 ; Bailone et al 2022 ). The use of nematode C. elegans for studies to the health effect and mode of action of complex plant extracts has also some advantages: nematodes are genetically identical, can be studies throughout their complete life cycle, are small, low cost, and have a well-documented and thoroughly mapped nervous system with comparable neurotransmitters like in the human brain.…”

New Psychoactive Substances: Major Groups, Laboratory Testing Challenges, Public Health Concerns, and Community-Based Solutions

“…Receptors' roles in the endocannabinoid system in zebrafsh and possible cannabis efects in humans have been debated by Bailone et al [94]. Synthetic cannabinoids contain no cannabidiol, potentially associated with the toxicity exerted by these compounds compared to natural cannabis [95].…”

“…Synthetic cannabinoids contain no cannabidiol, potentially associated with the toxicity exerted by these compounds compared to natural cannabis [95]. Synthetic cannabinoids would possess binding afnity and stronger potency compared to delta-9tetrahydrocannabinol at cannabinoid receptors [95][96][97], with full agonists properties compared to the partial agonist activities of delta-9-tetrahydrocannabinol, having potency 10 to 200 times greater than that of delta-9-tetrahydrocannabinol [93,94]. To further demonstrate this, Figure 2 shows the drug interactions and endocannabinoid pathways in the synapse.…”

Cannabidiol improves haloperidol-induced motor dysfunction in zebrafish: a comparative study with a dopamine activating drug

“…However, many factors remain unclear because the potential effects of cannabinoids on neurotransmission and pharmacological effects on motor function have not been fully elucidated (Campos et al 2016 ). Nevertheless, understanding the cannabinoid system in zebrafish could help establish a basis for investigating the effects of cannabinoids in humans (Bailone et al 2022 ).…”