Ibogaine, a psychoactive compound from a West African shrub, can damage brain cells in rats even after a single dose. In rats given 100 mg/kg, the cerebellum showed clear signs of neurodegeneration, specifically in Purkinje neurons. Similar damage occurred in all rats given 75 mg/kg, though the affected areas were narrower. At 50 mg/kg, only 2 of 6 rats showed damage, but those affected had patches of astrocyte activation. No damage was seen in rats given 25 mg/kg, suggesting this dose may be a safe threshold with no observable adverse effects. The findings highlight ibogaine's potential neurotoxicity, which is relevant given its use in addiction treatment.
Ayahuasca, a traditional Amazonian brew containing DMT from Psychotria viridis and harmine from Banisteriopsis caapi, produces psychoactive effects because harmine inhibits monoamine oxidase-A, preventing DMT's metabolism and increasing its systemic bioavailability. The brew shows potential therapeutic benefits for depression, anxiety, and substance use disorders. Researchers developed physiologically based pharmacokinetic (PBPK) models for DMT and harmine in rats and humans, accounting for multiple administration routes and harmine's inhibition of DMT metabolism in the liver and lungs. The models reasonably predicted plasma concentrations across dosing conditions. Simulations suggest that maintaining plasma concentration above a threshold may be more relevant for therapeutic effects than peak levels, offering a framework for safer dosing.