Analysis of the relationship of altered states of consciousness (ASC) to culture and human psychobiology provides guidance for new approaches for addressing substance abuse and dependence. While Western cultures have a long history of repressing ASC, cross-cultural research illustrates the ubiquitous human drive to alter consciousness and the near universality of institutionalized healing practices based on ASC. These may reflect adaptive mechanisms that do not operate in contemporary societies as they did in the human past. Effectiveness of ASC procedures in treating substance dependence is found in ethnomedical treatments of addiction, the addiction literature, Alcoholics Anonymous, and the physiological effects of shamanistic practices. A review of shamanic therapeutic mechanisms illustrates their applicability to addressing the psychodynamics of drug addiction. The utility of natural ASC practices to reduce substance dependence problems is illustrated by clinical research on the treatment of drug dependence through the use of meditative practice and models of their psychobiological dynamics. Shamanistic practices induce the relaxation response, enhance theta-wave production, and stimulate endogenous opioid and serotonergic mechanisms and their mood elevating effects. Directions of a shamanic based ASC therapy for drug dependence are suggested.