Abstract

Oral Tongue Squamous Cell Carcinoma (OTSCC) represents one of the most aggressive and challenging forms of head and neck cancers, often associated with poor prognosis and significant functional impairment. Despite advancements in surgery, radiotherapy, and chemotherapy, remains a need for supportive and integrative approaches that may enhance therapeutic outcomes and patient quality of life. Herein, we present a case report describing the use of an integrative therapeutic regimen combining medical cannabis, melatonin, and oxygen-ozone therapy in a patient with OTSCC. In 2021 the patient, a 43-year-old woman with a diagnosis of aggressive non-keratinizing squamous cell carcinoma of the left side of the tongue, underwent conventional oncological treatment, including surgical resection and adjuvant radiotherapy. Three months later, the clinical condition deteriorated, and neck, right arm, lung and liver metastasis were detected. Thus, an integrative protocol based on medical cannabis (standardized THC/CBD formulation), melatonin, oxygen-ozone therapy and Boswellia was introduced. Five months later, positron emission tomography scan detected no visible lesions.

In 2022, palmitoylethanolamide was introduced to the integrated therapy while the last cycle of oxygenozone was performed. Three months later, chemotherapy was discontinued because of a multi-resistant Staphylococcus Aureus infection. In 2023, a diagnostic follow-up evidenced a dimensional and metabolic increase of a pulmonary consolidation and the patient underwent localized radiotherapy. In 2024, there was no evidence of lesions. To date, the patient is considered cured and continues with the integrated therapy. No significant adverse effects were observed. The multimodal approach appeared to contribute positively to the patient’s functional recovery and psychological resilience during and after standard treatments. This case highlights the potential role of selected integrative therapies in the supportive care of patients with oral cancers. While further studies are required to evaluate the efficacy and safety of such approaches in larger cohorts, our experience suggests that medical cannabis, melatonin, and oxygenozone therapy may be valuable adjuncts in a multidisciplinary treatment strategy for OTSCC.

Keywords:Oral tongue squamous cell carcinoma; Medical cannabis; Melatonin; Oxygen-ozone therapy; Boswellia; Palmitoylethanolamide; Case report

Abbreviations:ACF: Aberrant Crypt Foci; C: Squamous Cell Carcinoma; CBD: Cannabidiol; CT: Chemotherapy; EGFR: Epidermal Growth Factor Receptor; EMT: Epithelial-Mesenchymal Transition; GPR: G-Protein-Coupled Receptors; FGF19: Fibroblast Growth Factor 19; GBM: Glioblastoma; HGF: Hepatocyte Growth Factor; HN : Head and Neck; HPV: Human Papillomavirus Infections; IGF-1: Insulin-Like Growth Factor 1; MMP-9: Matrix Metallopeptidase 9; MLT: Melatonin; OT: Oral Tongue; PEA: Palmitoylethanolamide; PPAR-α : Peroxisome Proliferator-Activated Receptor Alpha; PET: Positron Emission Tomography; ROS: Reactive Oxygen Species; RT: Radiotherapy; TERT: Telomerase Reverse Transcriptase; THC: Tetrahydrocannabinol; TMZ: Temozolomide; TP53: Tumor Protein 53; TRPV: Transient Receptor Potential Channels; OSCC: Oral Squamous Cell Carcinoma; VEGF: Vascular Endothelial Growth Factor; US: Ultrasound