People have long sought meaning and significance in their lives through a variety of spiritual practices including prayer, fasting, chanting, solitude, and meditation. Historically, some of these practices have included the use of certain psychoactive plants. A common theme of these experiences, with or without the aid of psychoactive agents, has been to free oneself of the bounds of everyday perception and thought in a search for universal truths and enlightenment. To a large extent, this type of subjective and uniquely human experience has enjoyed little credibility in the mainstream scientific world and, thus, has been given little scientific attention. However, it may be time now to recognize these extraordinary subjective experiences, even if they are, at present, not directly verifiable by objective measures and even if they sometimes involve claims about ultimate realities that lie outside the purview of science. The article by Griffiths et al. describes one of the first attempts to study these experiences in a systematic scientific investigation of the reportedly profound and sometimes lifealtering experiences induced by the powerful hallucinogen psilocybin. Their study is unique in several ways. First, it applies rigorous, modern methods of psychopharmacological research, including use of controlled, double-blind drug administration with a positive control drug and counterbalanced orders, standardized and replicable testing conditions, and sensitive outcome measures. Second, the study was conducted in specially designed environment, where the drug effects could be experienced safely yet unconstrained by an unnecessarily impersonal laboratory or clinical setting. Third, this is the first modern psychopharmacology study to focus, with healthy volunteers, upon experiences of deeply meaningful insights and understanding. Finally, the study is unique in that the investigators have also begun to study the lasting, life-changing effects that have been attributed to such experiences, using systematic follow-up assessments of mood and overt behavioral changes in the participants’ lives. The Editors invited commentaries from four experts to put this study in a larger context. These commentaries by Drs. Solomon Snyder, Charles R. Schuster, Herbert Kleber, and David Nichols provide a context for the study in terms of the history, policy, psychiatry, and future research. They relate this study historically to previous studies with hallucinogens and discuss the implications for drug and drug research policy. They discuss this class of drugs in terms of potentially adverse psychiatric consequences and also in terms of potential therapeutic applications. The commentaries identify important future directions for research on the neurochemistry and neurobiology of these drugs and these experiences. Taken together, these commentaries indicate that the Griffiths et al. study will likely take an important place in the history of human psychopharmacology research. It is time for psychopharmacologists to open their minds and their laboratories to the full domain of human drug experience. We would do well to be wary of our own preconceptions and prejudgments, and to be prepared to consider the entire scope of human experience and behavior as legitimate targets for systematic and ethical scientific investigation. Griffiths et al. set an excellent example for such a venture. Psychopharmacology (2006) 187:267 DOI 10.1007/s00213-006-0462-8