*Review* **Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles**

**Ronit Vogt Sionov \* and Doron Steinberg**

> The Biofilm Laboratory, The Institute of Biomedical and Oral Sciences, The Faculty of Dentistry, The Hebrew University—Hadassah Medical School, Jerusalem 9112102, Israel; dorons@ekmd.huji.ac.il **\*** Correspondence: ronit.sionov@mail.huji.ac.il

**Abstract:** Antibiotic resistance has become an increasing challenge in the treatment of various infectious diseases, especially those associated with biofilm formation on biotic and abiotic materials. There is an urgen<sup>t</sup> need for new treatment protocols that can also target biofilm-embedded bacteria. Many secondary metabolites of plants possess anti-bacterial activities, and especially the phytocannabinoids of the *Cannabis sativa* L. varieties have reached a renaissance and attracted much attention for their anti-microbial and anti-biofilm activities at concentrations below the cytotoxic threshold on normal mammalian cells. Accordingly, many synthetic cannabinoids have been designed with the intention to increase the specificity and selectivity of the compounds. The structurally unrelated endocannabinoids have also been found to have anti-microbial and anti-biofilm activities. Recent data sugges<sup>t</sup> for a mutual communication between the endocannabinoid system and the gu<sup>t</sup> microbiota. The present review focuses on the anti-microbial activities of phytocannabinoids and endocannabinoids integrated with some selected issues of their many physiological and pharmacological activities.

**Keywords:** anti-microbial activity; anti-biofilm activity; *Cannabis sativa* L.; endocannabinoids; gu<sup>t</sup> microbiota; pathogens; phytocannabinoids
