“Antimicrobial resistance remains a critical global health threat, driving the urgent need for novel therapeutic agents. Cannabinoids, bioactive secondary metabolites derived from Cannabis sativa, have gained attention for their promising antimicrobial properties.
This review presents the latest advances in the antimicrobial properties of cannabinoids, emphasizing their activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and selected Gram-negative bacteria.
We summarize their antibacterial and antifungal effects, along with insights into structure-activity relationships that reveal the critical roles of functional groups such as the resorcinol moiety and alkyl side chain.
Mechanistic studies suggest that membrane disruption, metabolic interference, and reactive oxygen species generation contribute to their antimicrobial action. Moreover, we summarize the synergistic potential of cannabinoids when used in combination with conventional antibiotics, highlighting both promising outcomes and notable limitations.
Despite these advances, challenges such as poor solubility, limited in vivo data, and regulatory barriers persist. Addressing these gaps through focused medicinal chemistry and translational research will be essential to harness the full potential of cannabinoids as next-generation antimicrobial agents.”
“Non-psychotropic Cannabis sativa L. chemotypes have gained increasing interest due to their diverse profiles of bioactive compounds. While cannabinoids such as cannabidiol (CBD), cannabigerol (CBG), are known for their biological effects, the role of other cannabinoids such cannabichromene (CBC) remains underexplored as for chemotype V, which lacks in cannabinoids but is characterized by other minor phytochemicals.
This study aimed to evaluate the individual and combined contributions of cannabinoids and non-cannabinoid phenolics to the antioxidant, antimicrobial, and anti-inflammatory properties of extracts derived from four C. sativa chemotypes, including a cannabinoid-free variant as a comparison.
Ethanolic extracts were obtained from four hemp chemotypes: CBD-rich (CS1), CBG-rich (CS2), CBC-rich (CS3), and cannabinoid-free (CS4). Phytochemical profiling was conducted using UHPLC-HRMS. Antioxidant properties were assessed via DPPH, ABTS, and FRAP assays. Antimicrobial activity was tested against Gram-positive and Gram-negative bacteria through MIC, MBC, and time-kill assays. Anti-inflammatory activity was evaluated in LPS-stimulated RAW 264.7 macrophages via gene expression analysis of pro- and anti-inflammatory mediators (IL1b, IL6, Cox2, IL10, IL1Ra).
Phytochemical analysis confirmed the chemotype-specific profiles, with CS3 showing the highest levels of canniprene and the early discovered 5-methoxy-dihydrodenbinobin. Antioxidant assays revealed that cannabinoids were the main contributors to radical scavenging capacity, though CS3 exhibited additional ferric ion reducing power likely due to non-cannabinoid phenolics. Antibacterial activity was confined to Gram-positive bacteria, where CS1 showed the highest efficacy, and CS4 showed no activity, highlighting the critical role of cannabinoids. All extracts reduced LPS-induced Il1b, Il6, and Cox2 gene expression, but only cannabinoid-rich extracts upregulated the anti-inflammatory cytokines IL10 and IL1Ra, indicating a cannabinoid-dependent effect.
Both cannabinoids and non-cannabinoid phenolics contribute to the biological activity of Cannabis sativa extracts, with cannabinoids playing a central role in antimicrobial responses and stronger anti-inflammatory effect as a pure cannabinoid or as an extract. From this point of view, the cannabinoid-free chemotype V could be a valuable functional control for isolating the effects of cannabinoids, reinforcing the need for integrative analyses in evaluating the therapeutic potential of cannabis-derived formulations.”
“In this study, we provided a phytochemical characterization and biological activity of non-psychoactive Cannabis sativa L. extracts from III, IV, V and the emerging CBC chemotype. The phytochemical profile confirmed the distinct percentage of cannabinoid and non-cannabinoid composition of each chemotype, with the CS3 sample exhibiting the highest levels of canniprene and 5-methoxy-dihydrodenbinobin. Antioxidant assays demonstrated that cannabinoids significantly contribute to the radical scavenging capacity of the extracts, with an additional support from non-cannabinoid phenolics as testified by the CS4. Antimicrobial assays showed that only the cannabinoid-containing extracts exhibited potent bactericidal activity against Gram-positive pathogens, including drug-resistant MRSA, while the cannabinoid-free extract lacked such activity. Furthermore, all extracts, including the cannabinoid-free one, were able to suppress LPS-induced pro-inflammatory gene expression in macrophages. However, only the cannabinoid-rich extracts promoted the anti-inflammatory cytokines IL-10 and IL-1Ra, underscoring a cannabinoid-dependent immunomodulatory effect.
Taken together, these results highlight the importance of cannabinoid in the biological properties of Cannabis sativa with a contribution apported by non-cannabinoid phenolic compounds. Moreover, the anti-inflammatory, antimicrobial, and antioxidant effects observed with both pure cannabinoids and cannabinoid-containing extracts support their potential use in topical formulation for the treatment of chronic inflammatory skin disorders, such as atopic dermatitis and psoriasis. These conditions are often exacerbated by skin dysbiosis and colonization by Gram-positive bacteria like Staphylococcus aureus, which contribute to skin barrier dysfunction and amplify immune dysregulation (Zhang et al. 2025). Therefore, while the cannabinoid-free chemotype V serves as a valuable control for dissecting the specific contributions of individual cannabinoids within CS extracts, our findings pave the way for future investigations into the therapeutic potential of selected cannabis-derived products—particularly in the context of antimicrobial resistance and inflammatory diseases associated with dysbiosis.”
“Cannabis compounds are well-known for their therapeutic applications in the treatment of various health issues.
These substances, mainly cannabinoids, are known for their antimicrobial properties and ability to interact with various cells through endocannabinoid receptors. However, the limitations of cannabis extract, particularly its viscosity, stickiness, and low bioavailability when applied topically, limit its use in dermatology.
To enhance topical applications for treating bacterial infections and dermatophytosis, cannabis extracts were encapsulated in chitosan nanoparticles, an easily accessible and cost-effective. Cannabis extracts were prepared from three cannabis strains differing in content of major cannabinoids, namely Chocolope (THCA-A), Jonas 1 (CBDA), and Hemp G (CBGA), and subsequently were encapsulated in chitosan nanoparticles. The resulting particles were characterized, and antimicrobial and cytotoxic activity was evaluated. The mean size of particles ranged from 89.1 ± 24.8 nm for empty nanoparticles to 355.6 ± 101.6 nm for particles containing Hemp G extract. Considering the extract:chitosan ratio (1:10 w/w, 1:20 w/w respectively) and the encapsulation efficiency (EE) range from 44.65 ± 4.39% to 94.44 ± 0.93%, total amount of extracts encapsulated in chitosan nanoparticles ranged from 2.96 ± 0.05 to 5.61 ± 0.19% in 1 g of chitosan nanopowder.
Most significant antimicrobial effect was observed against the fungi Nannizzia fulva CCF 6025, where the MIC80 of the pure extract from Jonas 1 variety was 256 μg/mL while the encapsulated extract in chitosan nanoparticles (1:10 w/w extract:chitosan ratio) inhibited growth at a concentration of 256 μg/mL of nanoparticles (corresponding to 13.05 ± 0.13 μg/mL of extract).
Overall, encapsulation reduced the amount of extract required to inhibit the growth of pathogenic microorganisms by up to several times, notably in case of dermatophytes, compared to non-encapsulated extracts. Encapsulation also reduced the cytotoxic effects of the extracts on human keratinocytes. Furthermore, pure high-THCA-A extract and encapsulated extract in chitosan nanoparticles slightly increased cell viability after 72 h exposure in low concentrations compared to control.
These results may suggest the chitosan nanoparticles-encapsulated formulations as a suitable topical delivery form of cannabis extracts, offering a possible adjunctive treatment of dermatophytosis and wound healing.”
“Aims: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired pneumonia with resistance against beta-lactam antibiotics. New, potent antibiotics against MRSA with other mechanisms of action are thus urgently needed. Recently, cannabinoids have been evaluated for antimicrobial activity in the ongoing search for new anti-infective agents, but their anti-biofilm effect has not been extensively studied. In this study, five main phytocannabinoids – canndibidiol (CBD), delta-9-tetrahydrocannabinol (THC), cannabinol (CBN), cannabigerol (CBG), and cannabichromene (CBC) were examined for their activity against a MRSA biofilm.
Methods and results: The anti-biofilm activity was assessed by crystal violet staining, resazurin metabolic assay, reactive oxygen species (ROS) assay, and propidium iodide membrane integrity test. The minimum inhibitory concentrations of all tested cannabinoids were between 1-2 µg/mL. CBN showed the most potent anti-MRSA biofilm activity, significantly reducing biofilm biomass and bacterial viability. It also induced the highest intracellular ROS levels. In contrast, CBD was the least effective among the tested cannabinoids in most of the anti-biofilm assays, yet it caused the greatest membrane damage to bacteria within the biofilm.
Conclusions: This study showed that despite being chemically similar, the cannabinoids demonstrated different potency and potentially different mechanisms of action against MRSA. More research is needed to investigate how they act on this pathogen and its biofilm.”
“Extensively drug-resistant (XDR) Acinetobacter baumannii poses a serious clinical challenge due to its resistance to nearly all available antibiotics, including carbapenems and colistin. Cannabidiol (CBD), a non-psychoactive phytochemical from Cannabis sativa L., has recently shown promising antimicrobial activity.
This study evaluates the antibacterial and anti-biofilm effects of CBD against XDR A. baumannii isolates and explores its mechanism of action and potential as an adjunct therapeutic agent.
Twenty-six A. baumannii isolates collected from ICU medical devices were identified using MALDI-TOF/MS. Antimicrobial susceptibility was assessed by disk diffusion and broth microdilution to determine MICs and MBCs for CBD and standard antibiotics. Synergistic effects were evaluated via checkerboard assays and FICI values. Biofilm inhibition and eradication were assessed using crystal violet and MTT assays. Time-kill studies, membrane integrity assays (DNA/protein leakage, NPN uptake, membrane depolarization), and scanning electron microscopy (SEM) were employed to investigate bactericidal kinetics and membrane-disruptive mechanisms.
CBD exhibited activity against antimicrobial resistance isolates (MIC: 3.9 to > 500 µg/mL). Remarkably, CBD synergized with gentamicin, meropenem, and colistin, reducing their effective concentrations by up to 1,000-fold. Combination therapy significantly inhibited and eradicated biofilms. Time-kill assays demonstrated rapid, concentration-dependent killing, with complete bacterial clearance at 4× MIC within 2 h. Mechanistic assays and SEM confirmed that CBD induces extensive membrane damage.
These findings highlight CBD’s potential as an effective adjunct to conventional antibiotics for treating XDR A. baumannii infections, offering a novel strategy to counteract antimicrobial resistance.”
“Acinetobacter baumannii is an opportunistic, Gram-negative bacterium that has emerged as a major cause of hospital-associated infections (HAIs) worldwide, with no standard therapeutic recommendation for its management and control. It primarily affects critically ill and immunocompromised patients, leading to severe infections such as ventilator-associated pneumonia, bloodstream infections, urinary tract infections, meningitis, and wound infections. A. baumannii’s remarkable ability to survive in hospital environments, resist desiccation, and persist on medical equipment—particularly in intensive care units (ICUs)—makes it a persistent challenge in healthcare settings.”
“Our study demonstrates that CBD exhibits potent antibacterial and anti-biofilm properties against XDR A. baumannii, particularly when used in combination with conventional antibiotics such as gentamicin, meropenem, and colistin. Notably, its ability to disrupt membrane integrity represents a key mechanism in overcoming drug tolerance.
These findings provide a strong foundation for further investigation of CBD as a novel therapeutic strategy to combat antimicrobial resistance in clinical settings.”
“Background: The accumulation of agri-food waste is a major environmental and economic challenge and converting these by-products into bioactive compounds fits within the circular bioeconomy. This study aimed to evaluate the antimicrobial potential of extracts derived from Cannabis sativa L. leaves (CSE), Crocus sativus tepals (CST), and Prunus avium L. cherry waste (VCE) against four key bacterial species (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa).
Methods: Minimum inhibitory concentration (MIC) assays were performed to assess antibacterial activity, while a bioinformatic pipeline was implemented to explore possible molecular targets. Full-proteome multiple sequence alignments across the bacterial strains were used to identify conserved, strain-specific proteins, and molecular docking simulations were applied to predict binding interactions between the most abundant compounds in the extracts and their targets.
Results: CSE and CST demonstrated bacteriostatic activity against S. aureus and B. subtilis (MIC = 15.6 mg/mL), while VCE showed selective activity against B. subtilis (MIC = 31.5 mg/mL). CodY was identified as a putative molecular target for CSE and CST, and ChaA for VCE. Docking results supported the possibility of spontaneous binding between abundant extract constituents and the predicted targets, with high binding affinities triggering a strong interaction network with target sensing residues.
Conclusions: This study demonstrates the antimicrobial activity of these agri-food wastes and introduces a comprehensive in vitro and in silico workflow to support the bioactivity of these agri-food wastes and repurpose them for innovative, eco-sustainable applications in the biotechnology field and beyond.”
“Given the observed antimicrobial activity against foodborne and surface-associated pathogens, the findings suggest that these extracts may hold promise for use in natural food preservation or environmental hygiene applications.The approach and the evidence adopted here and provided in this study could be useful for future for more eco-friendly and cost-effective strategies to develop waste-derived bioproducts for different purposes.”
“Innovative topical drug delivery systems, such as film forming systems, aim, among other objectives, to offer new application possibilities, enhance patient compliance, and provide prolonged therapeutic effects.
This study presents the development and comprehensive characterization of a novel chitosan-based film-forming system incorporating cannabidiol for antimicrobial topical treatment.
While chitosan and cannabidiol have been separately explored for their pharmaceutical properties, their combination within an in situ film-forming matrix remains largely unreported. Chitosan was chosen for its film-forming, mucoadhesive, and inherent antimicrobial properties. Ethanol-water ratios enabling optimal solubilization of chitosan were determined, and a suitable cannabidiol solubilizer was identified to ensure its homogeneous incorporation into the polymer matrix. The resulting films were characterized using differential scanning calorimetry, rheological analysis, Raman spectroscopy, optical microscopy, and scanning electron microscopy.
In vitro studies demonstrated sustained cannabidiol release, favorable mechanical properties, and excellent antimicrobial efficacy against both Gram-positive and Gram-negative bacteria, as well as fungi.
These results highlight the developed film-forming system as a novel and promising platform for the localized treatment of bacterial and fungal skin infections.”
“Shrimp aquaculture plays a crucial role in global food production but is increasingly threatened by viral and microsporidian pathogens such as White Spot Syndrome Virus (WSSV), Enterocytozoon hepatopenaei (EHP) and Infectious Hypodermal and Haematopoietic Necrosis Virus (IHHNV). Conventional reliance on antibiotics to combat these infections has raised serious concerns regarding antimicrobial resistance, environmental contamination and food safety. Additionally, environmental stressors such as salinity shifts and poor water quality exacerbate disease outbreaks, leading to severe production losses across Asia and Latin America.
To explore eco-friendly therapeutic alternatives, this study assessed the antiviral potential of cannabidiol (CBD), a bioactive compound extracted from Cannabis sativa seed oil, identified through GC-MS analysis.
Using molecular docking techniques, we evaluated CBD’s interactions with key viral proteins: VP28 of WSSV, the tubulin β-chain of EHP and the capsid protein of IHHNV. The docking results revealed strong binding affinities of -6.61 kcal/mol (EHP), -6.72 kcal/mol (IHHNV) and -5.38 kcal/mol (WSSV), indicating stable and potentially inhibitory interactions. Structural models were retrieved from RCSB PDB and SwissModel, while ligand preparation and docking were performed using AutoDock 4.2.
CBD also demonstrated favourable pharmacokinetic and safety profiles, with predictions indicating no mutagenicity, hepatotoxicity or cardiotoxicity, and acceptable drug-likeness characteristics.
Compared to other plant-derived compounds previously tested in shrimp disease models, CBD exhibited superior binding stability, more interaction residues and better bioavailability scores.
These findings highlight CBD as a promising dual-function agent, capable of both modulating shrimp immunity and directly inhibiting key viral pathogens.
These findings highlight cannabidiol (CBD) as a promising dual-action compound, with the potential to both enhance shrimp immune responses and exert direct antiviral effects against key pathogens. This study lays a robust groundwork for future in vivo validations, formulation strategies and regulatory frameworks, ultimately supporting the development of sustainable, precision-based aquaculture health management.”
“The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a critical threat to global health, creating an urgent need for novel antimicrobial agents.
In this study, we evaluated a small library of natural and semisynthetic phytocannabinoids against a broad panel of MDR Gram-positive bacterial strains, evidencing very good activity in the low µM range.
We provide evidence of the antibacterial activity of the two separated enantiomers of cannabidiol, offering novel insights into the stereochemical aspects of their bioactivity.
To investigate the possible molecular targets and clarify the mechanism of action, we employed Inverse Virtual Screening (IVS), a computational approach optimized for predicting potential protein-ligand interactions, on three selected MDR bacterial species. Interestingly, key targets belonging to important bacterial metabolic pathways and defense mechanisms were retrieved, and the results were used to rationalize the observed biological activities.
To the best of our knowledge, this study marks the first application of IVS to microorganisms, offering a novel strategy for identifying bacterial protein targets. The results pave the way for future experimental validation, structure-based drug design, and the development of novel antibacterial agents.”
“These findings suggest that these phytocannabinoids likely exert their antibacterial effects via multi-target inhibition, interfering with multiple essential bacterial pathways.”
“Objective: Cannabis sativa L. is aware of a rich source of bioactive substances with various structures that exhibit pharmacological activity in the central nervous system, cardiovascular, cerebrovascular, respiratory, reproductive, and gastrointestinal systems.
Materials and methods: In this study, cannabis sugar leaves were soaked in 99% ethanol, followed by evaporation. The antibacterial effect of the cannabis sugar leaf extract was then evaluated using the disc diffusion method. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined using broth dilution.
Results: The results of this study indicated that the cannabis sugar leaf extract inhibited Bacillus cereus, Vibrio cholerae, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis when compared to tetracycline, but it did not inhibit Pseudomonasaeruginosa. The MIC and MBC of the cannabis sugar leaves extract against B. cereus, V. cholerae, E. coli, S. aureus, and S. epidermidis were 0.977, 1.953, 31.25, 62.5, 125, 250, 250, 500, 250, and 500 mg/ml, respectively. The bioactive compounds in cannabis sugar leaf extract were identified using high-performance liquid chromatography.
Conclusion: The results indicated that the major bioactive compounds were Δ-9- tetrahydrocannabinol (THC) and cannabidiol (CBD). While minor bioactive compounds included gallic acid and tannic acid. These results support the benefits of cannabis sugar leaf extract, which has been used for its pharmacological properties and may be useful as an alternative antimicrobial agent in medicine.”
