Introduction: Cannabis has a historical role for pharmacological analgesia/anaesthesia, as well as for dental anxiety.Fast-forward to today's scientific literature, there are many considerations regarding the role of cannabis in dentistry.We examine the role of the endocannabinoid system and its modulation from the dental perspective.Whilst cannabis smoking has been associated with poor dental health, and tetrahydrocannabinol (THC) intoxication can result in tachycardia and acute hypertension, (which could cause drug-drug interaction with sedation and anaesthesia), some cannabinoids seem to be useful for a promising therapy for a range of different conditions of the oral cavity, such as peri-operative analgesia, several neurologic orofacial disorders, like burning mouth syndrome, or even dental anxiety and mouth inflammations.Aims: The aim of this study is to review the potential for applications of cannabis-based medications for the dental clinic as well as the risks for the oral cavity associated with cannabis consumption.Methods: Literature searches were conducted in MEDLINE/PubMed, Cochrane Central Register of Controlled Trials and Google Scholar from inception to February 2022.Study selection, data extraction, and quality assessment were conducted for references on cannabis in dentistry and endocannabinoid system in the oral cavity.Results: As a substantial proportion of adolescents and young adults are exposed to opioids through dental clinicians, it is important to consider that cannabis has also been proposed as a valuable tool for management of the «opioid epidemic», as it does not share the fatal risks such as respiratory depression associated with opioids, whilst providing many of the desired pain-relieving and sedative effects.Cannabinoid receptors not only mediate immunologic as well as pain signals, but are also expressed in periodontal and gingival tissues, as well as in both osteoblast and osteoclasts, making them potential targets for a number of new technologies: from implantology to anti-plaque mouthwashes.See Table 1 for some of the most researched potential uses.