Identification of cannabinoid-sensitive and -resistant oral bacteria

Marijuana, an emerging risk factor for periodontitis, contains multiple potent antibacterials, particularly the phytocannabinoids. Microbial dysbiosis is a hallmark of this destructive oral disease. We examined a panel of oral bacteria for susceptibility to the major cannabinoid, cannabidiol (CBD), portended by an initial <i>in vivo</i> microbiome analysis of marijuana users and non-users with periodontitis. Multiple oral bacteria were found to be sensitive to physiologically relevant CBD doses-<i>Aggregatibacter actinomycetemcomitans</i>, <i>Fusobacterium nucleatum</i>, several strains of <i>Porphyromonas gingivalis</i>, <i>Streptococcus mutans</i>, <i>Streptococcus gordonii</i> and <i>Tannerella forsythia</i>. Other oral bacteria, however, were resistant to even superphysiological CBD concentrations-<i>Campylobacter gracilis, Corynebacterium durum, Haemophilus parainfluenzae</i>, several oral <i>Treponema</i> species and <i>Veillonella parvula</i>. Enrichment of phytocannabinoid resistant bacterial pathobionts may help explain increased periodontitis prevalence in cannabis users who, like tobacco smokers, may have distinct therapeutic and preventive needs. To this end, a library of membrane permeabilizing peptoids (<i>N</i>-substituted glycine oligomers), based on an endogenous mammalian antimicrobial peptide, cathelicidin, was screened for activity against <i>Treponema denticola</i>. This spirochete was sensitive to a sub-set of stable and inexpensive antimicrobial peptoids that, presumably due to peptoid-induced outer membrane instability, also rendered CBD toxic to normally resistant spirochetes. The tobacco-stable, cannabinoid-labile pathobiont, <i>P. gingivalis</i>, was also sensitive to specific antimicrobial peptoids. Electron micrographs clearly suggest altered ultrastructure in both CBD-treated <i>P. gingivalis</i> and peptoid-exposed <i>T. denticola</i>. In summary, cannabis use may promote specific oral bacteria while suppressing others. The associated dysbiosis may help explain marijuana-exacerbated periodontitis. While more comprehensive studies of cannabis-induced microbial fluxes are warranted, adjunctive antimicrobial agents, such as cathelicidin-mimicking peptoids, that target cannabis-promoted pathobionts may also be worth exploring for therapeutic potential.