A method for decreasing
nicotine and other
substance use in humans is disclosed. Tetrahydroberberine (THB) and its analogs, l-
Tetrahydropalmatine (l-THP) and l-Stepholidine (l-SPD), are present in and can be isolated from several plants in the Magnoliidae superorder. According to the disclosed method, THB and its analogs are used to block
nicotine-induced DA release, and modulate
heterologous or homoeric expression of human nicotinic
acetylcholine receptors (nAChR) in humans. Specifically, THB exhibits bi-
directory modulation of α4β2-nAChR-mediated currents induced by
nicotine. THB also shows predominant inhibition on homologously expressed α7-nAChR function. Thus, according to the disclosed method, THB is used to simultaneous
blockade midbrain DA
system function, the brain reward center, and neuronal α4β2- and α7-nAChR function, the major nicotine targets in the brain. Therefore, THB and its analogs serve as a novel class of natural compounds to decrease nicotine dependence in humans. Furthermore other substances, such as
alcohol, cocaine, and opiates, also operate by triggering the brain reward center, resulting in a cycle of substance or
alcohol abuse. THB and its analogs can be used to decrease use of substances such as
alcohol, cocaine, and opiates. Finally, because THB and its analogs are DA antagonists, THB and its analogs can also be used as a treatment for Parkinson's
Disease, Alzheimer's
Disease and
Schizophrenia.