Dimethyltryptamine and harmine, components of ayahuasca, prevented cocaine-induced apoptosis in SH-SY5Y human neuroblastoma cells.

Ayahuasca is a psychoactive brew traditionally used in religious rituals by indigenous Amazonian populations and South American syncretic religions such as Santo Daime and União do Vegetal. Its psychoactive effects are primarily due to N,N-dimethyltryptamine (DMT), while harmine (HRE), a β-carboline alkaloid, inhibits monoamine oxidase (MAO), enabling DMT's oral bioavailability. Recent studies demonstrate Ayahuasca's therapeutic potential in treating substance use disorders, including cocaine use disorder, which involves neurotoxic effects. However, no in vitro studies to date have evaluated the neuroprotective potential of Ayahuasca compounds in this context. This study investigated the effects of DMT and HRE, isolated and combined, on cocaine-induced toxicity in human SH-SY5Y neuroblastoma cells. Cells were exposed for 48 h to various concentrations of DMT and HRE (0.1-1000 µM), cocaine (0.5-5 mM), and DMT:HRE combinations (10:10 to 10:100 µM). The non-toxic concentrations of DMT (10 µM) and HRE (10 µM), both isolated and combined (10:20 µM DMT:HRE), were co-incubated with the lethal concentration 50 (LC