Cannabidiol: an alternative therapeutic agent for oral mucositis?

Abstract

SUMMARYWhat is known and objective: Chemo-and radiotherapy are therapeutic modalities often used in patients with malignant neoplasms. They kill tumour cells but act on healthy tissues as well, resulting in adverse effects. Oral mucositis is especially of concern, due to the morbidity that it causes. We reviewed the literature on the etiopathogenesis of oral mucositis and the activity of cannabidiol, to consider the possibility of its use for the prevention and treatment of oral mucositis. Methods: We searched the PubMed database and selected complete articles published in English that met the inclusion criteria for the period 1998-2016. The search terms 'cannabinoids', 'cannabidiol', 'oxidative stress', 'antioxidants' and 'oral mucositis' were used. Results and discussion: The control of oxidative stress may prevent and alleviate oral mucositis. Studies have demonstrated that cannabidiol is safe to use and possesses antioxidant, antiinflammatory and analgesic properties. What is new and conclusions: The literature on the use of cannabidiol in dentistry is still scarce. Studies investigating the use of cannabidiol in oral mucositis and other oxidative stressmediated side effects of chemotherapy and radiotherapy on the oral mucosa should be encouraged. WHAT IS KNOWN AND OBJECTIVEWith an increase in life expectancy and an ageing population, the frequency of chronic non-communicable diseases such as cancer has been increasing. Consequently, there is a greater demand for antineoplastic treatments, which are responsible for major adverse effects. Oral mucositis (OM) is a complication commonly observed, particularly with radiotherapy (RT) of the head and neck area and with chemotherapy (CT). It is a painful and debilitating condition of varying severity. It is characterized by the presence of ulcerated lesions in the oral cavity, which usually leads to difficulty in eating and consequential loss of weight and malnutrition, and susceptibility to opportunistic infections. OM affects the quality of life of patients and can become a dose-limiting factor in treatment. [1][2][3][4][5][6] There is considerable evidence that the cytotoxic effects of CT and RT result from physico-chemical reactions that lead to excessive production of free radicals (FR), which favours an oxidant-antioxidant imbalance and oxidative stress (OS). This could mediate the development of oral lesions and OM. 4,5,[7][8][9][10][11] However, despite our understanding of the pathogenesis of this condition, its prevention and treatment are still considered a challenge to the dentist.The use of cannabinoids, components of Cannabis sativa, in the treatment of complex diseases has been extensively investigated in different medical areas. Among the cannabinoids, cannabidiol (CBD) is the non-psychotropic cannabinoid of greatest abundance in the plant.12 According to reported studies, CBD has antioxidant, anti-inflammatory and immunomodulatory properties and is devoid of psychoactive properties, and its minimal side effects make it safe for use in humans. [12][...

Double‐blind placebo‐controlled randomized clinical trial evaluating doxycycline effects on chemotherapy‐induced oral mucositis

“…The preventive and therapeutic role of antioxidant agents such as cannabidiol has been recently suggested. 37 It is probable that the complexity OM pathogenesis requires the incorporation of more than one intervention.…”

Cannabidiol on 5‐FU‐induced oral mucositis in mice

“…Many investigators have noted that the action of CBD on OS may be more potent than with classic anti-oxidants, such as α-tocopherol (Cuba et al, 2017;Klein et al, 2018;Koohi-Hosseinabadi et al, 2017). Considering that the increase in free radicals, evidenced by cellular damage caused by CT, is capable of generating an imbalance in OS and the production of pro-inflammatory mediators responsible for the tissue damage in OM, suggest that CBD is capable of acting both in OS control and in the suppression of the inflammatory response, playing a protective role in relation to OM.…”

“…Recent studies point to CBD as a promising alternative to conventional cancer treatment due to its ability to inhibit the proliferation, adhesion, migration, invasion, and angiogenesis of neoplastic cells. However, the molecular mechanisms involved in these properties are not well established and they depend on which neoplasms are to be treated and their drug (Cuba et al, 2017).…”

“…Cannabidiol (CBD) is a component of Cannabis sativa (marijuana), a plant that exerts potent anti-inflammatory, immunomodulatory, anti-oxidant, anti-emetic, and analgesic effects through the activation of cannabinoid receptors (CB1 and CB2) located in the central nervous system and immune cells (Lafaye, Karila, Blecha, & Benyamina, 2017;MacCallum & Russo, 2018). Studies have reported that CBD does not have psychotropic activity and exerts beneficial effects in neuropsychiatric diseases and inflammatory disorders (Booz, 2011;Burstein, 2015;Cassol-Jr et al, 2010;Cuba, Salum, Cherubini, & Figueiredo, 2017;Elbaz et al, 2015;Pan et al, 2009;Rajesh et al, 2010;Yang et al, 2014).…”

The effects of cannabis use on oral health

“…The anti-oxidant, anti-inflammatory, and analgesic properties of CBD have recently been reported as therapeutic and safe for use in oral mucositis (Cuba, Salum, Cherubini, & Figueiredo, 2017), despite the lack of evidence for the use of CBD in dentistry. Studies on the use of cannabinoids in oral mucositis and other oral mucosal diseases caused by oxidative stress, chemotherapy, or radiotherapy should be encouraged.…”