The phylum Proteo bacteria were decreased in cannabis smokers compared with those of non-smoking controls

The effects of cannabis on human health have been extensively studied, and public acceptance of cannabis for medicinal and recreational use grows worldwide.However, numerous studies in both humans and animals have demonstrated that cannabis use impairs neural functioning in a variety of cognitive and performance tasks, such as memory, learning, attention, perception, and motor coordination . Frequent cannabis smoking is associated with lower white-matter integrity , blunted psychotomimetic effects,perceptual alteration, cognitive impairment, and increasing cortisol levels .Some psychoactive components of cannabis were found to affect both neural and immune systems. D9-Tetrahydrocannabinol , a primary psychoactive component of cannabis, can directly bind to cannabinoid receptors, which are distributed extensively in the brain vertical grow system. THC also exhibits a wide range of immunosuppressive effects,which may decrease host defense to infections .

The connection and interaction between the gut microbiome and CNS functionvia the microbiota-gut-brain axis have been studied , but the oralcavity also hosts a large community of different bacteria that interact with each other and with the host. Healthy oral microbiomes resist pathogen colonization in the mouth , and when the oral microbiomeis compromised, opportunistic pathogenic bacteria may colonize and lead to new translocation events to the circulation that contribute to systemic disease pathogenesis . Oral bacteria canenter into the systemic circulation through inflamed gingiva and thereby affect peripheral organs and the CNS . In mice, oral administration of Campylobacter jejuni activated visceral sensory nuclei in the brainstem that processed gastro-intestinal sensory information ; Porphyromon as gingivalis, an oral pathogen contributing to the development of chronic periodontitis, may be a risk factor for developing amyloid-beta  plaques, cognitive impairment, and dementia . Further, exposure to viral or bacterial pathogens up regulates neuronal Ab expression in non-transformed cell culture models and wild-type rat brains, which may represent a naive antimicrobial defense response.

Cannabis smoking alters the oral environment and produces numerous chemicals that directly interact with oral bacteria. Some ofthe chemicals are toxicants and may perturb the oral microbial ecology.Whether chronic cannabis use affects CNS function through dysbiosis of oral microbiome remains unknown. In this study, we found that saliva Actinomyces, Veillonella, Megasphaera, and Streptococcus bacteria were increased, and Neisseria bacteria were decreased in cannabis smokers compared to non-smokers. Two Actinomyces speciesbacteria and one control Neisseria species bacterium  were inoculated to the B6 mice viaoral inoculation. A. meyeri administration resulted in reduced global mouse activity, macrophage infiltration, and increased Ab 42 protein production in the brain. For individuals with cannabis use disorder, we assessed exclusion arypsychiatric diagnoses using appropriate modules of the Mini-International Neuropsychiatric Interview, cannabis grow equipment as described in our previous study . Briefly, The M.I.N.I., a brief structured interview, was to assess current Diagnostic and Statistical Manual of Mental Disorders,5th edition  diagnoses. Because the M.I.N.I. only assesses current diagnoses and a more thorough history of substanceuse is needed, the substance use module of the Structured Clinical Interview for DSM-V was used for substance use disorder diagnosis.

Drug screens were performed using the on Trak test cup, an in vitrodiagnostic test for the qualitative detection of drug or drug metabolite in the urine. Results of urine screenings were used to substantiate self-reports of cannabis use. The saliva microbiome was analyzed and compared between cannabis smoking individuals and non-smoking control individuals. We found that cannabis smoking was associated with decreased oralmicrobial diversity compared to those in the non-smoking control group. The oral microbial communities differed in the two study groups reflected by the b-diversity.Next, we examined the relative abundance of individual bacterial taxa.At the genus level, enrichment of Neisseria was lower in cannabis smokers than innon-smokers; in contrast, Actinomyces, Veillonella, Megasphaera, and Streptococcus were found to increase among cannabis smokers. At the species level, 36 species were significantly differentin cannabis smokers compared to non-smoking controls after adjusting for multiple comparisons , including 16 species that were decreased and 20 species that were increased in cannabis smokers compared to non-smoking controls .