Ayahuasca is a psychedelic plant brew originating from the Amazon Rainforest. It is formed from two basic components, the Banisteriopsis caapi vine, and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. There has been a dramatic increase in interest surrounding ayahuasca since the turn of the millennium. Increasing numbers of tourists are travelling to the Amazon rainforest to drink the brew, with various media outlets, celebrities, and researchers describing benefit from its consumption. Ayahuasca is now present in every continent and retreat centres offering plant medicine experiences in the Amazon rainforest has become a thriving business. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. This thesis comprises five studies investigating Amazonian ayahuasca use. Initially, the pharmacology of the brew is explored in the form of a systematic review, concluding complex synergistic mechanisms may be present, although further research is needed. The remaining studies utilise observational methodology, investigating the impact of ayahuasca retreats following a traditional Shipibo lineage adapted for ayahuasca tourists in the Peruvian Amazon. The effects of the brew on personality, mental health outcomes, epigenetics, and nature relatedness are documented. Further, a phenomenological analysis of the ayahuasca experience is included. The research in this thesis is amongst the first to investigate Shipibo-style ayahuasca retreats in the Peruvian Amazon. Various ethical issues surrounding the increasing popularity of the brew and potential medicalisation are also discussed. It is hoped that this research will add to the growing body of knowledge surrounding the potential therapeutic effects of ayahuasca, whilst considering risks, ethics, and wider applications.