Ayahuasca, a psychoactive brew made from Banisteriopsis caapi and Psychotria viridis plants and used ancestrally by Amazonian populations and more recently by religious groups, causes developmental toxicity and behavioral changes in zebrafish embryos and larvae. Over 96 hours of exposure at concentrations from 0 to 1000 mg/L, the LC50 was 236.3 mg/L. Exposure led to hatching delay, loss of equilibrium, edema, and red blood cell accumulation, mainly at the highest concentration. Locomotor activity in larvae decreased at the highest concentration tested. These results align with mammal studies and highlight possible risks of uncontrolled ayahuasca use.
25I-NBOMe is significantly more cytotoxic than 2C-I in differentiated SH-SY5Y cells and primary rat cortical cultures, likely due to its higher lipophilicity. Both drugs cause severe mitochondrial dysfunction, including decreased ATP levels and mitochondrial membrane depolarization, without significant changes in reactive oxygen or nitrogen species. 25I-NBOMe also elevates intracellular calcium levels. Apoptosis occurs with both drugs, but 2C-I additionally induces autophagy and strong caspase-3 activation, suggesting caspase-3-dependent apoptosis, while 25I-NBOMe may trigger caspase-3-independent apoptosis through calcium dysregulation and direct mitochondrial damage. Mitochondrial dysfunction and calcium dysregulation are central to the neurotoxicity of these NPS.