Cannabis-Linked Oral Bacteria Can Reach the Brain and Cause Anxiety in Mice

Actinomyces species, previously found to be enriched in chronic cannabis smokers' oral microbiome, induced anxiety-like behaviors in mice when inoculated orally. The bacteria produced metabolites (arginine and argininosuccinate) that increased in both oral swabs and brain tissue, causing mitochondrial dysfunction, oxidative stress, and reduced GABAergic neurotransmission. Notably, the bacteria themselves did not travel to the brain; their metabolites did.

Wild-type C57BL/6 mice received oral inoculation with cannabis use-associated Actinomyces species. Behavioral testing assessed anxiety. Brain analysis measured microglia activation, mitochondrial function, and GABA signaling. In vitro experiments tested Actinomyces-produced metabolites on neurons.

This is a novel oral-brain axis discovery. It suggests that some anxiety associated with chronic cannabis use might not be caused by cannabinoids directly but by changes in oral bacteria that cannabis smoking promotes. This opens an entirely new avenue for understanding cannabis-related neuropsychiatric effects.

The oral-brain metabolic axis is an emerging concept. This study suggests that cannabis's effects on mental health may extend beyond direct cannabinoid actions to include microbiome-mediated pathways. If confirmed in humans, it could explain some of the variability in cannabis-anxiety relationships.

Animal study with bacterial inoculation, not natural cannabis use. Preprint (not yet peer-reviewed). Cannot determine if findings apply to human cannabis users. Single bacterial genus tested. Cannot distinguish cannabis-specific effects from general oral microbiome effects.