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      Cannabinoids Drugs and Oral Health—From Recreational Side-Effects to Medicinal Purposes: A Systematic Review

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          Abstract

          Background: marijuana, the common name for cannabis sativa preparations, is one of the most consumed drug all over the world, both at therapeutical and recreational levels. With the legalization of medical uses of cannabis in many countries, and even its recreational use in most of these, the prevalence of marijuana use has markedly risen over the last decade. At the same time, there is also a higher prevalence in the health concerns related to cannabis use and abuse. Thus, it is mandatory for oral healthcare operators to know and deal with the consequences and effects of cannabis use on oral cavity health. This review will briefly summarize the components of cannabis and the endocannabinoid system, as well as the cellular and molecular mechanisms of biological cannabis action in human cells and biologic activities on tissues. We will also look into oropharyngeal tissue expression of cannabinoid receptors, together with a putative association of cannabis to several oral diseases. Therefore, this review will elaborate the basic biology and physiology of cannabinoids in human oral tissues with the aim of providing a better comprehension of the effects of its use and abuse on oral health, in order to include cannabinoid usage into dental patient health records as well as good medicinal practice. Methods: the paper selection was performed by PubMed/Medline and EMBASE electronic databases, and reported according to the PRISMA guidelines. The scientific products were included for qualitative analysis. Results: the paper search screened a total of 276 papers. After the initial screening and the eligibility assessment, a total of 32 articles were considered for the qualitative analysis. Conclusions: today, cannabis consumption has been correlated to a higher risk of gingival and periodontal disease, oral infection and cancer of the oral cavity, while the physico-chemical activity has not been completely clarified. Further investigations are necessary to evaluate a therapeutic efficacy of this class of drugs for the promising treatment of several different diseases of the salivary glands and oral diseases.

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          Most cited references156

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          The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.

          The PRISMA statement is a reporting guideline designed to improve the completeness of reporting of systematic reviews and meta-analyses. Authors have used this guideline worldwide to prepare their reviews for publication. In the past, these reports typically compared 2 treatment alternatives. With the evolution of systematic reviews that compare multiple treatments, some of them only indirectly, authors face novel challenges for conducting and reporting their reviews. This extension of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement was developed specifically to improve the reporting of systematic reviews incorporating network meta-analyses. A group of experts participated in a systematic review, Delphi survey, and face-to-face discussion and consensus meeting to establish new checklist items for this extension statement. Current PRISMA items were also clarified. A modified, 32-item PRISMA extension checklist was developed to address what the group considered to be immediately relevant to the reporting of network meta-analyses. This document presents the extension and provides examples of good reporting, as well as elaborations regarding the rationale for new checklist items and the modification of previously existing items from the PRISMA statement. It also highlights educational information related to key considerations in the practice of network meta-analysis. The target audience includes authors and readers of network meta-analyses, as well as journal editors and peer reviewers.
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            Molecular characterization of a peripheral receptor for cannabinoids.

            The major active ingredient of marijuana, delta 9-tetrahydrocannabinol (delta 9-THC), has been used as a psychoactive agent for thousands of years. Marijuana, and delta 9-THC, also exert a wide range of other effects including analgesia, anti-inflammation, immunosuppression, anticonvulsion, alleviation of intraocular pressure in glaucoma, and attenuation of vomiting. The clinical application of cannabinoids has, however, been limited by their psychoactive effects, and this has led to interest in the biochemical bases of their action. Progress stemmed initially from the synthesis of potent derivatives of delta 9-THC, and more recently from the cloning of a gene encoding a G-protein-coupled receptor for cannabinoids. This receptor is expressed in the brain but not in the periphery, except for a low level in testes. It has been proposed that the nonpsychoactive effects of cannabinoids are either mediated centrally or through direct interaction with other, non-receptor proteins. Here we report the cloning of a receptor for cannabinoids that is not expressed in the brain but rather in macrophages in the marginal zone of spleen.
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              Structure of a cannabinoid receptor and functional expression of the cloned cDNA.

              Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS) in a complex and dose-dependent manner. Although CNS depression and analgesia are well documented effects of the cannabinoids, the mechanisms responsible for these and other cannabinoid-induced effects are not so far known. The hydrophobic nature of these substances has suggested that cannabinoids resemble anaesthetic agents in their action, that is, they nonspecifically disrupt cellular membranes. Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids. Here we report the cloning and expression of a complementary DNA that encodes a G protein-coupled receptor with all of these properties. Its messenger RNA is found in cell lines and regions of the brain that have cannabinoid receptors. These findings suggest that this protein is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                03 August 2021
                August 2021
                : 22
                : 15
                : 8329
                Affiliations
                [1 ]INSERM, U1215 NeuroCentre Magendie, Endocannabinoids and Neuroadaptation, University of Bordeaux, 33063 Bordeaux, France
                [2 ]Department of Interdisciplinary Medicine, University of Study “Aldo Moro”, Policlinico, 70124 Bari, Italy; ad.inchingolo@ 123456libero.it (A.D.I.); angeloinchingolo@ 123456gmail.com (A.M.I.); giuseppinamalcangi@ 123456libero.it (G.M.); luigi.santacroce@ 123456uniba.it (L.S.); denisahazballa@ 123456gmail.com (D.H.); mtdoria51@ 123456gmail.com (M.T.D.); drciroisacco@ 123456gmail.com (C.G.I.); giannadipalma@ 123456tiscali.it (G.D.); francesco.inchingolo@ 123456uniba.it (F.I.)
                [3 ]Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, 66100 Chieti, Italy; ascarano@ 123456unich.it
                [4 ]Department of Oral Rehabilitation, Faculty of Dentistry, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
                [5 ]Kongresi Elbasanit, Rruga: Aqif Pasha, 3001 Elbasan, Albania
                [6 ]Department of Medical and Biological Sciences, University of Udine, via delle Scienze, 206, 33100 Udine, Italy
                [7 ]Human Stem Cells Research Center HSC, Ho Chi Minh 70000, Vietnam
                [8 ]Embryology and Regenerative Medicine and Immunology at Pham Chau Trinh, University of Medicine, Hoi An 51300, Vietnam
                [9 ]Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania Luigi Vanvitelli, via Luigi de Crecchio, 680138 Naples, Italy; ludovica.nucci@ 123456unicampania.it (L.N.); rosario.serpico@ 123456unicampania.it (R.S.); maria.contaldo@ 123456unicampania.it (M.C.)
                [10 ]UOC Maxillo-Facial Surgery and Dentistry, Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, University of Milan, 20100 Milan, Italy; gianluca.tartaglia@ 123456unimi.it (G.M.T.); marco.farronato@ 123456unimi.it (M.F.)
                [11 ]Hospital A.O.S.G. Moscati, Contrada Amoretta, cap, 83100 Avellino, Italy; giovanniellodelia@ 123456gmail.com
                Author notes
                [* ]Correspondence: luigi.bellocchio@ 123456inserm.fr (L.B.); drlorussofelice@ 123456gmail.com (F.L.); roxana.bordea@ 123456ymail.com (I.R.B.); Tel.: +33646298623 (L.B.); +39-32-8213-2586 (F.L.); +40-74-4919319 (I.R.B.)
                [†]

                These authors contributed equally to this work as co-first authors.

                [‡]

                These authors contributed equally to this work as co-last authors.

                Author information
                https://orcid.org/0000-0002-6366-1039
                https://orcid.org/0000-0002-2660-9231
                https://orcid.org/0000-0001-9745-7506
                https://orcid.org/0000-0001-5671-8124
                https://orcid.org/0000-0003-1374-6146
                https://orcid.org/0000-0001-7166-9949
                https://orcid.org/0000-0002-8160-3342
                https://orcid.org/0000-0002-9376-8152
                https://orcid.org/0000-0002-4773-6694
                https://orcid.org/0000-0002-6209-9873
                https://orcid.org/0000-0002-5947-8987
                https://orcid.org/0000-0003-3797-5883
                Article
                ijms-22-08329
                10.3390/ijms22158329
                8347083
                34361095
                47232bd8-6a8b-4a06-9256-ad4e879644ca
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 15 July 2021
                : 02 August 2021
                Categories
                Review

                Molecular biology
                oral health,cannabis,therapeutic adjuvant,mouth diseases
                Molecular biology
                oral health, cannabis, therapeutic adjuvant, mouth diseases

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