A substance extracted from the Amazonian vine Banisteriopsis caapi was shown in the 1920s to alleviate parkinsonism. These pioneering studies were criticized and forgotten for a number of reasons, including questions as to the identity of the active agent and failure to conduct strictly controlled studies. We now report the first double-blind, randomized placebo-controlled trial of a Banisteriopsis caapi (BC) extract for treatment of Parkinson’s disease (PD). A single dose of BC administered to de novo PD patients resulted in significant improvement in motor function evidenced by decline in the Unified Parkinson’s Disease Rating Scale (UPDRS) score. The beneficial e!ects were maximal by the second hour and persisted until the last evaluation of the patients at 4 hours. However, tremor was not improved and in some patients tremor was exacerbated. All patients also experienced a degree of transient nausea or vomiting. We measured the concentrations of the putative active agents (harmine, harmaline, and tetrahydroharmaline), and hypothesize that the beneficial e!ects were primarily due to glutamate receptor antagonist actions of the harmalines.