Cannabis extracts as modulators of bone mineralization and regenerative repair: Evidence from a Zebrafish Model

Akeem George Smith 1, Nyron Nembhard 2, Shahane Stephenson 2, Wayne St. Orville Palmer 1, Machel Anthony Emanuel 3 and Mohammad Kutub Ali 2, *

1 Department of Orthopedics, University Hospital of the West Indies Kingston, Jamaica.
2 Department of Basic Medical Science, Faculty of Medical Sciences, University of West Indies, Mona campus, Kingston, Jamaica, West Indies.
3 Department of Life Science, Faculty of Science and Technology, University of West Indies, Mona campus, Kingston, Jamaica, West Indies.

 

Research Article
World Journal of Advanced Pharmaceutical and Life Sciences, 2026, 11(01), 071–081.
Article DOI: 10.53346/wjapls.2026.11.1.0016
Publication history: 
Received on 26 May 2026; revised on 30 June 2026; accepted on 02 July 2026
 
Abstract: 
Background: Cannabis-derived constituents can modulate vertebrate tissue regeneration, offering mechanistic insight into how bioactive compounds influence limb- or fin-like skeletal structures. Zebrafish fin regeneration is a well-established model for studying blastema dynamics, osteoblast function, and mineralization programs, and is sensitive to chemical perturbations that affect morphogenesis and mineral deposition. Cannabis components Tetrahydrocannabinol (THC), Cannabidiol (CBD), and terpenes are known to elicit distinct developmental and morphogenetic effects in zebrafish models, with evidence for entourage-like interactions and varied impacts on mineralization and tissue architecture.
Objective: To quantify regenerative length as a proportion of pre-amputation fin across a 15 days’ timeline in a controlled zebrafish caudal-fin amputation model, comparing mock controls to three cannabis-associated exposure paradigms (Δ9-THC, CBD, terpenes). To delineate how constituent classes influence wound healing morphogenesis, mineralization, and regenerative architecture relative to controls, and to explore potential timing and composition-dependent interactions.
Methods: Using a standardized amputation protocol, adult zebrafish were allocated to mock, THC, CBD, or terpenes treatment groups within a multi-component exposure framework. Fin regeneration was quantified as percent restoration of the original fin length at serial time points (up to 15 days). Histology of crushed lepidotrichia and Alizarin Red staining assessed mineralization and ray repair. Group differences were evaluated via multi-time-point comparisons, with reported significance (p < 0.0001) at multiple time points.
Results: Controls followed canonical regeneration with rapid outgrowth and patterning; >50% restoration early post-amputation and near-complete regeneration later. Terpenes produced the strongest impairment (final ≈40% of original fin), followed by CBD, then THC (terpenes > CBD > THC). Early points (≤ day 5) showed THC-related attenuation of impairment relative to CBD, indicating distinct temporal control of regeneration by each constituent class. Histology revealed convergence of repair signals across groups, but terpene-treated fins displayed hollow-like morphologies and node-like disruptions, while THC/CBD-exposed fins exhibited intensified Alizarin Red staining in crush zones, suggesting altered mineralization despite reduced gross regeneration.
Conclusion: Cannabis-derived constituents modulate fin morphogenesis and mineralization, with terpene-rich exposures most disruptively influencing regenerative architecture. The findings support entourage-like interactions shaping vertebrate bone/regenerative responses and underscore exposure composition and timing as critical determinants of regenerative outcomes. Future work should probe terpene-driven osteogenic signaling and blastemal patterning mechanisms across regimens. Since heterotopic ossification involves dysregulated osteogenic signaling and ectopic mineralization, understanding how cannabinoids modulate these pathways could help identify potential targets to prevent or slow pathological bone growth. Although the current findings are preliminary and derived from a regenerative model, they provide a foundation for future studies investigating whether cannabinoid-related compounds could play a role in controlling or modulating the biological processes underlying heterotopic ossification.
 
Keywords: 
Zebrafish; THC; CBD; Terpenes; Caudal Fin; Regeneration
 
Full text article in PDF: