Intranasal Terpene Treatment for Glioblastoma: the Neuro-Oncological Potential of Perillyl Alcohol

Abstract

Glioblastoma is the most aggressive and fatal primary brain tumor in adults, characterized by poor prognosis and limited treatment efficacy due to the impermeability of the blood-brain barrier (BBB) and its treatment-resistant nature. This review aims to evaluate the potential of intranasal terpene treatment (ITT) as a novel and non-invasive strategy to bypass the BBB and improve glioblastoma treatment outcomes. A review of recent preclinical and clinical studies on intranasally administered compounds (especially terpenes such as Perillyl alcohol (POH)) is presented in terms of their molecular mechanisms, bioavailability, and clinical effects in the central nervous system (CNS). © 2025 Elsevier B.V., All rights reserved.