Dennis McKenna’s research has focused on the interdisciplinary study of Amazonian ethnopharmacology and plant hallucinogens. He has conducted ethnobotanical fieldwork in the Peruvian, Colombian, and Brazilian Amazon. His doctoral research (University of British Columbia, 1984) focused on the ethnopharmacology of ayahuasca and oo-koo-hé, two tryptamine-based hallucinogens used by indigenous peoples in the Northwest Amazon.

He is a founding board member of the Heffter Research Institute, and was a key organizer and participant in the Hoasca Project, the first biomedical investigation of ayahuasca use by the UDV, a Brazilian religious group. He was an adjunct professor in the Center for Spirituality and Healing at the University of Minnesota, and is the president and founder of the McKenna Academy of Natural Philosophy.