This paper examines the use of psychoactive substances such as Psilocybin, Mescaline, and LSD as adjuncts to mystical, religious or spiritual experiences. There is an analysis of the psychological changes and the changes in perception that these substances cause and how these can be interpreted as contributing to religious or spiritual enlightenment. There is also a discussion on the nature of what could be considered a religious experience. An overview of the use of such ‘entheogenic’ drugs from an historical perspective follows, looking specifically at the use of Soma and its importance in the establishment of Hinduism; the Kykeon of the Eleusinian Mysteries in Ancient Greece; and the use of the sacred mushroom ‘teonanacatl’ and its place in Central and South American Cultural History. Current use of entheogens will be discussed, focusing on the use of Peyote by the Native American Church and the use of Ayahuasca by the Santo Daime and União de Vegetal (UDV) in Brazil. Walter Pahkne’s ‘Experimental Examination of the Claim that Psychedelic Drug Experience May Resemble Mystical Experience’ (also known as the ‘Good Friday Experiment’) into the use of psilocybin in facilitating religious experiences is described and evaluated. The results of Pahnke’s experiment are compared to Griffiths et al’s 2006 study that sought to evaluate whether psilocybin can occasion mysticaltype experiences having substantial and sustained personal meaning and spiritual significance. The paper ends with a critical evaluation of the validity of drug-induced mysticoreligious experiences and discusses and evaluates the objections to the use of entheogenic drugs particularly within the traditional religious framework of ‘Western Society’.