Experimental Study on the Protective and Anti-venomous Effect of Medicinal Cannabis Oils with CBD or THC Enriched with Terpenes and Flavonoids from Cannabis sativa: An Experimental Prospecting Study.

• Grant number: 25/04557-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2025
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Marcos Hikari Toyama
• Grantee: Adeilso Bispo dos Santos Junior
• Host Institution: Instituto de Biociências (IB-CLP). Universidade Estadual Paulista (UNESP). Campus Experimental do Litoral Paulista. São Vicente , SP, Brazil

Abstract

Snake envenomations represent a serious public health issue in tropical and subtropical regions, associated with high morbidity and mortality. Although antivenoms neutralize protein toxins, they fail to control cellular, oxidative, and inflammatory damage caused by phospholipases A2 and serine proteases, resulting in necrosis, myotoxicity, and organ dysfunction. This highlights the need for adjuvant therapies for tissue protection and recovery. In this context, Cannabis sativa oils (full spectrum) stand out for their anti-inflammatory, antioxidant, and analgesic potential. The synergy between phytocannabinoids, terpenes, and flavonoids may amplify these effects, offering a promising approach to mitigate both systemic and local damage caused by snake venom, although it has been little explored experimentally.This study aims to investigate the protective and anti-venomous effect of Cannabis sativa oils enriched with CBD or THC, combined with terpenes and flavonoids, against the venoms of Bothrops jararacuçu and Crotalus durissus terrificus. The research will adopt an integrated approach, including molecular modeling (in silico), in vitro assays, and in vivo experiments. In silico studies will identify potential ligands between Cannabis compounds and molecular targets such as sPLA2, serine proteases, and acetylcholinesterase. The selected compounds will be tested in enzymatic assays and in vivo, evaluating parameters such as oxidative stress, inflammation, edema, myotoxicity, and liver and kidney lesions. The chemical composition of the oils will be characterized by HPLC and mass spectrometry. The hypothesis is that the synergy between cannabinoids, terpenes, and flavonoids will enhance the modulation of inflammation, oxidative stress, and pain, contributing to the neutralization of toxic venom effects and tissue preservation. If proven, this approach could enable innovative adjuvant therapies based on Cannabis sativa, with application in endemic regions where access to conventional antivenoms is limited.