Cannabis and Microbiome: A Systematic Review and Meta-Analysis

Background Cannabis is being legalized in many countries for therapeutic and recreational purposes. The cannabinoid compounds are mainly involved in the host metabolism under the endocannabinoid system, and they regulate the intestinal microbiota via an immunomodulatory mechanism leading to obtaining positive effects on the gastrointestinal and immunological systems. Objective The review is to systematically evaluate their association and the impact of the microbiome on cannabis treatment to support further clinical trials. Methods Utilizing online sources like PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library , a literature search was carried out up to July 20, 2022. The search was restricted to adults with clinical abnormalities and the use of English. An examination of predetermined subgroups under various disease conditions was carried out. The data was combined quantitatively. Result The study comprised 9 studies with 2526 participants; two were clinical trials and the others were observational studies. One significant factor influencing microbiota variation was marijuana (MJ) usage [R2=0.01, p=0.14]. In HIV patients who used MJ, there were elevated levels of Fusobacterium and Anaerotruncus and lower concentrations of Dorea . The genus Rothia was dominant, but Capnocytophaga, Fusobacterium , and Porphyromonas were low at the tongue site, whereas high Selenomonas and low Streptococcus were detected at the oral pharynx region in MJ users in oral cancer patients. Following cannabis use, Lactobacilli and S. mutan were increased in patients with musculoskeletal discomfort. Increases in the circulation of endocannabinoids are associated with an increase in SCFA-producing bacteria and a decrease in the proinflammatory species Collinsella in patients with knee arthritis. Lower Prevotella:Bacteroides ratios were more frequently linked to higher lifetime MJ consumption in those with cognitive impairments (p=0.052). Increased PEA excretion correlated with decreased microbial diversity, which caused anhedonia/amotivation to worsen. A. muciniphila was substantially more prevalent in obese patients after OEA administration. Conclusion Data from a systematic review suggest that cannabis usage and supplementation of medical cannabis in a variety of clinical problems had links with altering the human microbiome on gut, oral, rectal, and vaginal discharge. It must be taken into consideration in future research on the therapeutic effects of cannabis on patients. Short Summary As cannabis use is being legalized in more and more countries, it is important to observe how the use of cannabis affects the human body, particularly in those suffering from various clinical conditions. Using the qualitative data collected from the systematic review, it was found that cannabis use in adults with a range of different clinical conditions has associations with altering the human microbiome, a factor that must be considered in future studies of cannabis treatment for beneficial or detrimental effects on patients. Registration ID PROSPERO 2022 CRD42022354331 ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Department of Thai Traditional and Alternative Medicine (DTAM). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript as supplementary files. * CENTRAL : Cochrane Central Register of Controlled Trials CIs : Confidence intervals GRADE : Grading of Recommendation Assessment, Development and Evaluation NOS : Newcastle - Ottawa Quality Assessment Scale PRISMA-P : Preferred Reporting Items for Systematic review and Meta-analysis Protocols RCTs : Randomized controlled trials ROBINS-I : Risk Of Bias In Non-randomized Studies - of Interventions US : United States