CINC-PSR

Inhibiting CYP2A6 with 1,8-Cineole: A Proof-of-Concept study for Smoking Reduction

Project Overview

This project aims to generate pre-clinical in vivo proof-of-concept that 1,8-cineole (CN)—an authorized herbal medicine—inhibits the nicotine-metabolizing enzyme CYP2A5 (mouse orthologue of human CYP2A6), prolonging systemic nicotine exposure and reducing voluntary nicotine intake in mice. By converting previous in vitro laboratory findings into an in vivo efficacy package, the project seeks to validate CN as a candidate adjunct for smoking reduction and cessation. Because 1,8-cineole has an established human safety profile, positive findings will facilitate accelerated translation into clinical evaluation. Considering that 1.2 billion are smokers, smoking is responsible for 7 million deaths per year, and that many people try to quit, but cannot due to genetic predisposition that makes current NRT ineffective, such herbal medicine can potentially enhance smoking reduction,

Objectives:

• Enzyme Inhibition in Mice: Determine in vivo whether 1,8-cineole inhibits the nicotine-metabolizing enzyme CYP2A5 in mice.
• Human-Equivalent Dose Evaluation: Assess whether 1,8-cineole, administered at the maximum daily human-equivalent dose, sufficiently inhibits nicotine metabolism to support smoking reduction applications.
• Behavioral Efficacy Assessment: Evaluate using a two-bottle choice paradigm whether administration of 1,8-cineole significantly decreases voluntary nicotine consumption in mice, and decreases nicotine metabolism.

The Project “Inhibiting CYP2A6 with 1,8-Cineole: A Proof-of-Concept study for Smoking Reduction/ CONCEPT/0525/035” is implemented through the «Proof of Concept for Technology / Knowhow Applications» Programme, under the programme of social cohesion “THALIA 2021-2027”, co-funded by the European Union through Research and Innovation Foundation.