“Fungal infections pose a major threat to human health with increasing incidence of antifungal resistance globally. Despite the need for novel antifungal drugs, few are currently in clinical development.

Here we evaluate the antifungal activity of five phytocannabinoids against several clinically relevant fungal pathogens, with a focus on the priority pathogen Cryptococcus neoformans.

Our results demonstrate that Cannabidiol (CBD), and particularly Cannabidivarin (CBDV), have broad activity against C. neoformans and other fungal pathogens, including dermatophytes that cause common tinea. We found that both CBD and CBDV acted in a fungicidal manner and prevented biofilm formation in C. neoformans.

Phytocannabinoid treatment impeded factors important for virulence and antifungal resistance, including reduced capsule size and disruption of mature biofilms. Proteomics analysis revealed that the antifungal activity of CBD and CBDV was linked to destabilisation of the membrane, alterations in ergosterol biosynthesis, disruption of metabolic pathways, as well as selective involvement of mitochondrial-associated proteins. We next tested the ability of CBD to topically clear a C. neoformans fungal infection in vivo using the Galleria mellonella burn wound model, and we observed greatly improved survival in the CBD treated larvae.

This study illustrates the potential of phytocannabinoids as antifungal treatments and opens up new routes towards development of novel antifungal drugs.”

https://pubmed.ncbi.nlm.nih.gov/40470967/

“Fungal infections are a major public health issue affecting over a billion people globally. Current antifungal treatments are increasingly compromised by drug resistance and show adverse side effects, underscoring the urgent need for novel therapies.

Phytocannabinoids like Cannabidiol (CBD) and Cannabidivarin (CBDV), which have established safety profiles and are approved or under investigation for neurological conditions, may hold promise in this domain. Despite this, their antifungal properties remain underexplored.

Here we show that CBD and CBDV exhibit in vitro antifungal activity against various fungi, including common dermatophytes causing “jock itch” and “athlete’s foot”, as well as WHO Critical Priority pathogens, such as Cryptococcus neoformans. Further investigation in C. neoformans revealed that CBD and CBDV appear to work by disrupting biofilms, altering fungal cell morphology, and impacting metabolic pathways and membrane integrity, as observed through comparative proteomics. Further, in vivo experiments using Galleria mellonella infected with C. neoformans revealed significantly improved survival with CBD treatment.

The in vitro and in vivo antifungal efficacy of CBD and CBDV established in this study highlights the potential of phytocannabinoids to address the pressing need for effective and new treatments for fungal infections.”

“Overall, this study highlights promising antifungal properties of the phytocannabinoids CBD and CBDV against select fungal pathogens. We demonstrated not only their fungicidal activity against C. neoformans, but also their potential effectiveness against wider Cryptococcus strains, various other yeasts, and moulds including common dermatophytes, emphasizing their potential broader applicability in the clinic and the community.

We demonstrated that the phytocannabinoids appear to work via disrupting biofilms and altering cell morphology, while clear impacts on metabolism and membrane production could be observed with comparative proteomics. We finally showed that for the commonly available CBD, in vivo survival of G. mellonella was significantly boosted after C. neoformans infection, emphasizing the clear potential of CBD as an antifungal.

Taken together, the demonstrated efficacy of CBD and CBDV as broad antifungal agents, coupled with their established safety profile, makes them an exciting resource as a foundation for the development of future therapeutic interventions.”

https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013081