Repellent, Lethal Activity, and Synergism of Cannabis sativa Extracts with Terpenes Against a Laboratory Colony of Triatoma infestans

<i>Triatoma infestans</i> is one of the primary vectors of Chagas disease. This vector has developed increasing resistance to pyrethroids, the main insecticides used for its control. Recent studies have highlighted the repellent and lethal effects of <i>Cannabis sativa</i> on insects, suggesting its potential use in pest management. Based on this, we hypothesize that <i>C. sativa</i> could be a viable bioactive for controlling <i>T. infestans</i>. To test this hypothesis, acetone and ethanol extracts were obtained from the inflorescences of <i>C. sativa</i> L. (Deep Mandarine variety) using sonication. These extracts were analyzed through gas chromatography and high-performance liquid chromatography. The repellent and lethal effects of the extracts were evaluated on fifth-instar nymphs of <i>T. infestans</i> from a laboratory colony, as well as on the beneficial non-target species, <i>Apis mellifera</i>. The most abundant terpenes identified were <i>β</i>-caryophyllene and <i>β</i>-pinene, with concentrations exceeding 100 ppm in both extracts. Cannabidiol and Δ⁹-tetrahydrocannabinol were the predominant cannabinoids. Both extracts exhibited maximum lethal activity 48 h after insect contact, with the acetone extract demonstrating a potency five times greater than the ethanolic extract. Binary combinations of <i>C. sativa</i> extracts with major terpenes showed dose-dependent interactions against <i>T. infestans</i>, ranging from strong synergy (e.g., AE + <i>β</i>-caryophyllene, CI = 0.06-0.17) to marked antagonism (e.g., AE + <i>E</i>-ocimene, CI = 1.60-4.80). Furthermore, the acetone extract showed a more effective repellent action compared to the ethanol extract, even outperforming N,N-Diethyl-meta-toluamide (DEET, positive control). At a concentration of 25 µg/cm² for 60 min, the acetone extract achieved a 100% repellent effect, whereas DEET required a concentration of 50 µg/cm² to achieve the same effect. Unlike imidacloprid (positive control), neither extract showed toxicity to adult <i>A. mellifera</i> at the evaluated doses.