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The widespread use of Ayahuasca is not restricted to the indigenous peoples of the Amazon; it can also be found in the mestizo populations in the rural and urban areas of countries like Colombia, Peru and Brazil. In such places, Ayahuasca is used for the purpose of healing and other ritualistic activities where the boundaries that divide indigenous traditions from elements of other cultures, often become blurred. 

Approximately eighty years ago, non-indigenous groups who incorporated the use of Ayahuasca into their religious rituals began appearing in Brazilian cities in the Acre and Rondônia State. Santo Daime, União do Vegetal, and Barquinha are the most representative religions that first appeared in the Brazilian Amazonian cities and later expanded across the main Brazilian cities as well as Europe, the United States and Asia. The religious use of Ayahuasca by these groups is characteristically syncretic, where elements from Christianity, afro-Brazilian religiosity and indigenous shamanism are blended.

Today, a growing number of Europeans and North Americans make the pilgrimage to Amazonian countries like Brazil, Peru and Colombia, searching for their own, personal experience with Ayahuasca in a traditional ritualistic setting. Other Western seekers often search for South American shamans and curanderos who offer traditional Ayahuasca sessions within their own countries. 

More recently, the role of Ayahuasca in psychotherapy is found in contemporary society, where traditional ceremonial practice with Ayahuasca is accompanied by a preparation and integration process based on modern, psychotherapeutic methodology. In these groups, the focus lies on personal growth, psychotherapy and addiction recovery. Other groups integrate elements of Occidental psychotherapy directly into the Ayahuasca session itself, creating a neo-shamanistic ritual setting which often incorporates Eastern philosophies.

There are anecdotal reports, as well as preliminary studies in animals and in humans, suggesting therapeutic potentials for Ayahuasca or for some of its alkaloids. Some studies suggest that Ayahuasca can improve mental health, especially in problems such as drug dependence and depression.