NEUROPROTECTIVE POTENTIAL OF DIMETHYLTRIPTAMINE AND HARMINE, COMPONENTS OF AYAHUASCA, ISOLATED AND IN ASSOCIATION, IN SH-SY5Y NEUROBLASTOMA CELLS FACED BY COCAINE-INDUCED NEUROTOXICITY

• Grant number: 22/15813-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2023
• End date: December 31, 2024
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Raphael Caio Tamborelli Garcia
• Grantee: Gabriela Salles dos Santos
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Ayahuasca is a psychoactive tea used by the indigenous people of the Amazon in shamanic rituals as well as by religious groups such as União do Vegetal and Santo Daime in their rituals. This tea is traditionally made by infusing Psychotria viridis and Banisteriopsis caapi. While Psychotria viridis contains N,N-dimethyltryptamine (DMT), which is biotransformed by intestinal monoamine oxidase (MAO), Banisteriopsis caapi contains the beta-carbolines harmine, harmaline, and tetrahydroharmine, which inhibit MAO activity. This allows DMT to interact with serotonin receptors in the central nervous system, thus causing the psychedelic effects of tea. Several studies have investigated the pharmacological potential of ayahuasca in different scenarios, but the scientific literature lacks information about its toxicity and its neuroprotective role. This study aims to evaluate the neurotoxicity of different preparations of ayahuasca and its isolated active compounds (DMT and harmine) in SH-SY5Y human neuroblastoma cell culture, as well as to evaluate their possible neuroprotective effects in the same SH-SY5Y cells exposed to the lethal concentration 50 (LC50) of cocaine (2.5 mM). For that, we will generate the concentration-response curves of each batch of teas and their active compounds. Subsequently, the lowest concentration of each tea and actives in which no toxic effect is observed (NOAEL) will be incubated in the presence of cocaine's LC50. This study will be conducted using MTT cell viability assay and flow cytometry with 48 hours of exposure.