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 .alpha.4.beta.2-nAChR-mediated currents induced by nicotine. THB also shows predominant inhibition on homologously expressed .alpha.7-nAChR function. Thus, according to the disclosed method, THB is used to simultaneous blockade midbrain DA system function, the brain reward center, and neuronal .alpha.4.beta.2- and .alpha.7-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.