This article examines drug substitution with regard to hallucinogens (ayahuasca, ibogaine, peyote and LSD) set within the concept of redemption. The model examines both religious and secular approaches to the contemporary use of hallucinogens in drug substitution, both by scientists and in religious settings worldwide. The redemptive model posits that the proper use of one psychoactive substance within a spiritual or clinical context helps to free an individual from the adverse effects of their addiction to another substance and thus restores them as functioning members of their community or group.Data is drawn from the U.S., Brazil, Peru, and WestAfrica.Two principle mechanisms for this are proposed: the psychological mechanism of suggestibility is examined in terms of the individual reaching abstinence goals from addictive substances such as alcohol and opiates. Neurophysiological and neurochemical mechanisms to understand the efficacy of such substitution are highlighted from ongoing research on hallucinogens. Research by two of the authors with the Unaio do Vegetal (UDV) Church in Brazil is examined in terms of the model.