Ayahuasca is a brew made of two admixture plants containing dimethyltryptamine (DMT) and β-carbolines (harmine and tetrahydroharmine). The indigenous groups of the Amazonas basin have been using it for centuries as an ethnomedical substance in healing and spiritual-religious rituals. During the last two decades the brew has raised increased scientific and public interest worldwide about its healing effects. Present paper addresses the therapeutic potentials of ayahuasca use and outlines the cellular mechanisms behind – in focus of the σ-1 receptor mediated action of DMT. The scientific investigation of ayahuasca is complicated by methodical problems, legal issues, and sociocultural preconceptions. Key Words : ayahuasca, dimethyltryptamine, endoplasmic reticulum stress, ischemia-reperfusion injury, neurodegenerative diseases, neuroprotection, oxidative stress, serotonin receptor, σ-1 receptor