Cannabinoids and Cancer in Zebrafish: A Systematic Review

Josue Munguia
University of Miami

Co-authors: Josue F. Munguia¹, Mark Moffat¹, Anthony Alfonso¹, Ciné Brown¹, Amrit Baral^1,2, Denise C. Vidot^1
1University of Miami, ²Johns Hopkins University

Background: The recent rescheduling of cannabis has opened opportunities for research using this substance medicinally. Zebrafish Danio rerio are a useful model for cancer research because they share around 70% of their DNA with humans and grow tumors that closely resemble human cancers. Cannabinoids interact with the endocannabinoid system to influence cell growth, immune function, and other cancer-relevant pathways, yet no prior review has synthesized the use of zebrafish to study the intersection of cannabinoids and cancer.

Objectives: The objective of this review was to assess the current state of the literature on zebrafish as a model for studying cannabinoids and cancer.

Methods: Articles were retrieved from PubMed and Web of Science and screened for eligibility in Covidence by three independent reviewers using a predefined PICOS framework. Search matrices were established as follows: “Zebrafish AND (Cannabinoids OR Cannabis OR CBD OR THC OR Marijuana)”, “Zebrafish AND (Cannabinoids OR Cannabis OR CBD OR THC OR Marijuana) AND Cancer”. Inclusion criteria included in vivo exogenous phytocannabinoid exposure in zebrafish, published after January 1, 2013. Exclusion criteria included endocannabinoid exposure, in vitro studies, other animal models, and other published reviews.

Results: Out of 664 articles imported, 45 studies met final inclusion criteria. Results showed CBD was the most frequently studied phytocannabinoid, followed by THC and CBN. Studies also showed these phytocannabinoids being used to compare their effects with other synthetic substances. Most of the included studies focused on embryonic development and disease treatments rather than cancer-specific outcomes. No published studies found in this review examined phytocannabinoids and cancer within zebrafish. Two studies examined endocannabinoids and cancer; however, they were not included in this review since they did not meet inclusion criteria.

Conclusion: These results highlight the knowledge gap we are trying to address. Recent federal reclassification of cannabis from Schedule I to III may mitigate the dearth in knowledge as researchers use zebrafish as a model for translational work at the intersection of cannabinoids and cancer. Despite the exclusion of the two endocannabinoid and cancer articles, it is still important to acknowledge their existence underlining the necessity for phytocannabinoid research in this area.