Avaliação in vitro da atividade anti-Leishmania de fitocanabinoides de Cannabis sativa

Abstract

Leishmaniasis is considered a neglected tropical disease affecting socially vulnerable populations, with an estimated 1.5 to 2 million new cases annually. Leishmania spp. is an obligate intracellular parasite that exhibits two evolutionary stages: the extracellular promastigote form and the intracellular amastigote form. Regarding the clinical aspects of leishmaniasis, the disease presents in cutaneous, mucocutaneous, and visceral forms, the latter being the most severe and lethal. Despite its epidemiological relevance, pharmacotherapy remains largely unchanged, with drugs exhibiting high toxicity, administration difficulties, and the development of parasite resistance. Given the potential of Cannabis sativa as a source of bioactive compounds with pharmacological properties used in the treatment of epilepsy and Alzheimer's disease, other antibacterial, antifungal, antiparasitic, and anti-inflammatory activities have already been studied. Therefore, this study aims to evaluate the in vitro biological activity of different extracts rich in phytocannabinoids (CBG, CBD, THC, and THCV) against L. infantum forms, as well as their effect on the production of reactive oxygen species (ROS) by monocytes during infection. To this end, cultures of promastigotes, amastigotes, erythrocytes, and peripheral blood mononuclear cells (PBMCs), infected and uninfected, were treated with the phytocannabinoid extracts. The activity of the extracts in killing the different parasite forms, cytotoxicity on human cells, and ROS production were evaluated. The results showed that the phytocannabinoids exhibit anti-promastigote and anti-amastigote activities and moderate cytotoxicity against PBMCs, without evidence of erythrocyte hemolysis. Furthermore, CBD, CBG, and THCV reduced ROS production in infected monocytes. These results suggest that Cannabis sativa extracts may help control the parasite and modulate the inflammatory response. However, further studies are needed to elucidate the mechanisms involved and to further evaluate the safety profile, considering the potential use of phytocannabinoids as a therapeutic alternative in leishmaniasis.