Cannabinoids as Antibacterial Agents: A Systematic and Critical Review of In Vitro Efficacy Against Streptococcus and Staphylococcus

Abstract

Background: Two major bacterial pathogens, Staphylococcus aureus and Streptococcus pyogenes, are becoming increasingly antibiotic-resistant. Despite the urgency, only a few new antibiotics have been approved to address these infections. Although cannabinoids have been noted for their antibacterial properties, a comprehensive review of their effects on these bacteria has been lacking.

Objective: This systematic review examines the antibacterial activity of cannabinoids against S. aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains, and S. pyogenes.

Methods: Databases, including CINAHL, Cochrane, Medline, Scopus, Web of Science, and LILACS, were searched. Of 3510 records, 24 studies met the inclusion criteria, reporting on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration of cannabinoids.

Results: Cannabidiol (CBD) emerged as the most effective cannabinoid, with MICs ranging from 0.65 to 32 mg/L against S. aureus, 0.5 to 4 mg/L for MRSA, and 1 to 2 mg/L for VRSA. Other cannabinoids, such as cannabichromene, cannabigerol (CBG), and delta-9-tetrahydrocannabinol (Δ9-THC), also exhibited significant antistaphylococcal activity. CBD, CBG, and Δ9-THC also showed efficacy against S. pyogenes, with MICs between 0.6 and 50 mg/L. Synergistic effects were observed when CBD and essential oils from Cannabis sativa when combined with other antibacterial agents.

Conclusion: Cannabinoids' antibacterial potency is closely linked to their structure-activity relationships, with features like the monoterpene region, aromatic alkyl side chain, and aromatic carboxylic groups enhancing efficacy, particularly in CBD and its cyclic forms. These results highlight the potential of cannabinoids in developing therapies for resistant strains, though further research is needed to confirm their clinical effectiveness.

Keywords: Staphylococcus; Streptococcus; antibacterial; antimicrobial resistance; cannabinoids; dermatological conditions; infection; infectious skin diseases; medicinal cannabis; skin infections.

Figure 9

Four main sites for structurally and biologically diverse cannabinoids.

Figure 1

Study selection flow diagram.

Figure 2

A comparison of cannabinoids demonstrating in vitro activity against S. aureus (MIC values < 16 mg/L) in a blood-free medium. Cannabidiol (CBD) also reported an MIC of 32 mg/L [64]. The mean and standard error of the mean (excluding outliers) are shown for compounds with multiple MIC values. Abbreviations used in this Figure are listed at the end of this article.

Figure 3

A comparison of cannabinoids with in vitro MIC values (<16 mg/L) against MRSA. Compounds such as CBDA, CBNA, and THCV with MIC values ≥ 16 mg/L were excluded from the graph. Mean MIC and standard error are shown for compounds with multiple values. Abbreviations are listed at the end of the article.

Figure 4

Comparison of cannabinoids demonstrating in vitro activity against S. pyogenes (CBD MIC: 32–50 mg/L; THC MIC: 50 mg/L). The mean and standard error are presented for compounds with multiple MIC values, excluding outliers. Abbreviations used in this Figure are provided at the end of the article.

Figure 5

Structures of cannabinoids active against S. aureus, MRSA, and S. pyogenes; CBD is also active against VRSA. The list of abbreviations used in this Figure are given at the end of this article.

Figure 6

Structures of cannabinoids active against both S. aureus and MRSA (but not S. pyogenes). The list of abbreviations used in this Figure are given at the end of this article.

Figure 7

Structures of cannabinoids active against S. aureus. The list of abbreviations used in this Figure are given at the end of this article.

Figure 8

Structures of cannabinoids active against MRSA only. The list of abbreviations used in this Figure are given at the end of this article.