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.

The authors have declared no competing interest.

This study was funded by the Department of Thai Traditional and Alternative Medicine (DTAM).

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