Cannabis-Microbiome Interactions in Varied Clinical Contexts: A Comprehensive Systematic Review

Background As cannabis legalization extends to numerous countries, encompassing both medicinal and recreational applications, understanding its impact on human body is crucial. The endocannabinoid (eCB) system, regulated by naturally occurring (endogenous) and externally derived (exogenous) cannabinoid compounds, plays a pivotal role in the host’s metabolism. This system, in conjunction with the host’s immunomodulatory mechanisms, influences the composition of the gut microbiota, resulting in beneficial outcomes for the gastrointestinal (GI) and immunological systems. Objective This systematic review aims to evaluate the association between cannabis treatment and the gut and oral microbiome, supporting further clinical trials in this area. Methods A comprehensive literature search was conducted on online platforms such as PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library . The search encompassed studies published until July 20, 2022, focusing on adult populations with clinical abnormalities. Only English language studies were included. Identified studies were analyzed, considering predetermined subgroups based on different disease conditions. A random-effects meta-analysis was employed to qualitatively and quantitatively combined and assess the data. Result The study comprised 9 studies with 2526 participants, including 2 clinical trials and several observational studies. The research explored the impact of marijuana (MJ) use on the microbiota across various clinical categories, such as HIV infection, pain/inflammation, systemic aspergillosis, obesity, cognitive deficits, and oral diseases. Qualitative analysis of the included studies revealed diverse and condition-specific effects of MJ use on the microbiota, such as decreased microbial diversity and increased cannabinoid excretion. Conclusion These findings shed light on the complex effects of cannabis use on the human microbiota, underscoring the need for furture research on the therapeutic potential of cannabis. This review provides valuable insights to guide future investigations in this field. Funding None ![Figure][1] Short Summary With the global expansion of cannabis legalization, understanding the effects of cannabis on the human body, particularly among individuals with diverse clinical conditions, is of paramount importance. Through a meticulous systematic review utilizing comprehensive data, our findings uncover that cannabis consumption in adults with varied clinical conditions leads to discernable alterations in the human microbiome. These noteworthy modifications necessitate careful consideration in future investigations exploring the potential beneficial or adverse effects of cannabis treatment on patients. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### 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 [1]: pending:yes