The Development of levo-Tetrahydropalmatine as a Treatment for Nicotine Addiction

Abstract

The negative consequences of nicotine use are well known and documented, however, abstaining from nicotine use and achieving abstinence poses a major challenge for the majority of nicotine users trying to quit. l-Tetrahydropalmatine (l-THP), a compound extracted from the Chinese herb Corydalis, has been used clinically in China for over 40 years as a sedative and analgesic. l-THP has also displayed utility in the treatment of drug addiction, particularly cocaine and heroin addiction. The objective of this dissertation was to investigate if the utility of l-THP could be extended to include treatment of nicotine addiction. As such, the effect of l-THP treatment on abuse-related effects of nicotine was assessed in various behavioral models of nicotine addiction. Once the utility of l-THP was determined, the efficacy of l-THP was tested against varenicline and bupropion, FDA approved treatments for nicotine addiction. To better understand neurochemical changes that occur with l-THP administration, microdialysis experiments were performed where it was found that l-THP interacts with the mesolimbic dopamine system, a prominent pathway of drug addiction. The efficacy of l-THP in the treatment of various models of nicotine addiction and its interaction with the mesolimbic dopamine system make l-THP an attractive compound to study concerning nicotine addiction. Given the long standing safe use of l-THP in China and this new preclinical data, l-THP warrants further study and development for the treatment of nicotine addiction.