Nanomaterials are promising for addressing the major health challenges faced globally due to their particular characteristics, based primarily on their size, distribution, and morphology [1,2]. Metallic nanoparticles (MNPs) are widely used in biomedical fields including drug delivery, imaging, cancer treatment, sensing and gene manipulation [3,4,5]. This widespread use is due to their unique properties, such as a high surface area-to-volume ratio and their ability to be conjugated with antibodies, ligands, and drugs [6,7]. Among all MNPs, silver nanoparticles (AgNPs) stand out in the field of nanotechnology, sparking unlimited interest due to their chemical stability, and most importantly, their antibacterial, antiviral, antifungal, and anti-inflammatory activity [8,9]. They can be part of wound dressings, topical creams, or antiseptic formulations, as their antimicrobial action is explained by generating alterations in the unicellular membranes of bacteria, disrupting their enzymatic activities [10,11]. However, chemically synthesized AgNPs (cAgNPs) used in these products, along with their by-products, can be toxic and harmful to humans and the environment [12]. In an effort to counter these limitations, green synthesis methods have been employed to produce biogenic AgNPs that are more biocompatible with less collateral toxic effects [13,14,15].

Researchers are actively seeking sustainable, eco-friendly alternatives to conventional chemical synthesis. This has significantly advanced green synthesis procedures, particularly plant-mediated synthesis, where plant extracts act as both reducing and stabilizing agents [16,17]. This innovative approach has gained importance as a highly efficient, convenient, fast, ecological, and non-toxic technique for the synthesis of AgNPs [18,19,20]. Various plant components, including barks, roots, stems, fruits, seeds, calluses, peels, leaves, and flowers have been used for nanoparticle synthesis [21,22,23,24,25,26]. The key to this methodology lies in the crucial role of the phytochemicals produced by the plant [27,28]. These natural compounds, mostly water-soluble, include terpenes, polyphenols, flavones, carboxylic acids, carbohydrates, alkaloids, phenolic acids, and proteins, and are responsible for the bioreduction of silver ions during synthesis. Reported studies have emphasized the importance of specific functional groups within these phytochemicals, particularly alkaloids, flavones, and anthracenes, characterized by their –C=C–, –C–O, –C–O–C–, and –C=O– groups, to produce AgNPs [24,29].

In many cases, the reducing agents found in plant extracts serve both protective and stabilizing functions. This eliminates the need to add potentially toxic external chemical compounds [30,31]. AgNPs synthesized from plant extracts are usually more stable and tend to exhibit a wide range of shapes and sizes. Different parameters can be tested during synthesis, including temperature, pH, reaction time, and the concentration of plant extract and silver precursor. This technique also offers an efficient and rapid route, with a higher yield of nanoparticle synthesis, avoiding the complex and slow processes associated with maintaining cell cultures, as often required in other biological methods [13].

Particularly, AgNPs synthesized employing plants exhibit distinct advantages for biomedical applications, owing to the therapeutic properties of secondary metabolites present in the plant extracts used for their synthesis [32,33,34]. For Cannabis sativa L., numerous green syntheses of nanoparticles have been reported along with their promising biological activities [35,36,37,38]. The biological activity of AgNPs can be enhanced by the therapeutic properties contributed by C. sativa, such as analgesic, antioxidant, and anti-inflammatory properties, but also by the inherent antimicrobial properties of the cannabinoids. It has been reported that cannabinoids, terpenes, and phenolic compounds contribute to antibacterial activity through complementary mechanisms. Cannabinoids, like cannabidiol (CBD), are known to affect bacterial membrane integrity, particularly in Gram-positive strains, leading to increased permeability and cell damage [39]. Terpenes, due to their lipophilic nature, can also disrupt membrane structures and enhance the penetration of other bioactive compounds. Phenolic compounds, including flavonoids and phenolic acids, exhibit antibacterial effects via multiple pathways, such as enzyme inhibition, protein denaturation, and induction of oxidative stress. Overall, the combined presence of these compounds may result in an enhanced therapeutic effect of the green synthesized AgNPs [40,41,42]. However, the aqueous extract used as a reducing agent does not contain cannabinoids or terpenes, which are the most relevant lipophilic molecules of the plant. This is because the parts used for synthesis are not the inflorescences but other plant organs such as roots, bark, seeds, or even leaves [43,44,45].

This study aims to investigate the phytochemical potential of three distinct chemovars of C. sativa for the efficient green synthesis of AgNPs using ethanolic extracts from their inflorescences. In contrast to previous research that predominantly employed leaf material or other organs [43,44,45], this work focuses on inflorescences due to their richer content of cannabinoids and other bioactive secondary metabolites. This approach pursues to emphasize the relevance of full-spectrum compositions in cannabis extracts, particularly considering the reported ‘entourage effect’ [46], where synergistic interactions among metabolites may enhance biological activity.

In this context, the selection of C. sativa inflorescences is based on their unique phytochemical diversity. Specifically, cannabinoids like CBD possess phenolic hydroxyl groups that efficiently reduce silver ions (Ag⁺) to metallic silver (Ag⁰), while the complex chemical structure of these metabolites and associated terpenes provides natural capping and steric stabilization. As a recognized medicinal plant, utilizing these inflorescence-derived compounds imparts an intrinsic therapeutic ‘added value’ to the nanoparticles. By leveraging the synergistic potential between the plant’s bioactive constituents (e.g., anti-inflammatory or analgesic properties) and the antimicrobial silver core, this method offers an enhanced potential for biomedical applications compared to traditional chemical synthesis. Ultimately, the objective of this comprehensive profiling is to identify which chemovar presents the most promising phytochemical profile for the sustainable and efficient production of bioactive nanomaterials.