Concomitant consumption of marijuana, alcohol and tobacco in oral squamous cell carcinoma development and progression: Recent advances and challenges

Oral squamous cell carcinoma (OSCC) corresponds to 95% of all malignant tumours of the mouth. The association between alcohol and tobacco is the major risk factor for this disease, increasing the chances for the development of OSCC by 35-fold. The plant, Cannabis sativa is smoked as cigarettes or blunts and is commonly used in association with tobacco and alcohol. Any type of smoking habit exposes individuals to a wide range of carcinogens or pro-carcinogens, such as polycyclic aromatic hydrocarbons, as well as some ethanol derived substances such as acetaldehyde (AA), and all are genotoxic in the same way. In addition, ethanol acts in the oral mucosa as a solvent and therefore increases the cellular membrane permeability to carcinogens. Carcinogens found in tobacco are also concentrated in marijuana, but the latter also contains high levels of cannabinoids, bioactive compounds responsible for several effects such as euphoria and analgesia. However, Δ9-tetrahydrocannabinol (Δ9-THC), the major psychotropic cannabinoid found in plants, causes a reduction of cellular metabolism and induction of apoptosis, both of which are anti-neoplastic properties. Apart from limited epidemiologic and experimental data, the effects of concomitant chronic exposure to marijuana (or Δ9-THC), tobacco and alcohol in OSCC development and progression is poorly known. This paper reviews the most recent findings on the effects of marijuana over cellular proliferation, as well as in the risk for OSCC, with emphasis on its interaction with tobacco and ethanol consumption.