Drug addiction is an epidemic problem affecting millions worldwide with high rates of morbidity and mortality. Although the number of pharmacological options available to treat addiction has increased, these treatments demonstrate only modest efficacy. New treatments with improved efficacy rates and favorable side effect profiles are needed. Ayahuasca is a medicine that is increasingly being utilized to treat addictions. However, despite its growing popularity, the mechanisms underlying ayahuasca’s effectiveness as a treatment for addictions remain unknown. We propose biochemical, physiological, psychological, and transcendent hypotheses to explain how ayahuasca treats addictions.