The discovery of a number of hallucinogens in the 1950's and observations of their effects on perception, affect and behavior prompted hypotheses that the syndrome known as schizophrenia might be caused by an error in metabolism that produced such hallucinogens in the human brain, forming a schizo- or psycho-toxin (Osmond and Smythies, 1952).
This sequence of events formed the link between modern science and the historical use of many DMT-containing plants as a cultural and religious ritual sacrament (McKenna et al., 1998), their effect on the psyche and the chemical structure of N, N-dimethyltryptamine. DMT's hallucinogenic properties were not discovered until 1956 when Stephen Szara, a pioneering Hungarian chemist and psychiatrist, extracted DMT from the Mimosa hostilis plant and administered the extract to himself intramuscularly (Szára, 1956). In 1946 the microbiologist Oswaldo Gonçalves de Lima discovered DMT's natural occurrence in plants (Goncalves de Lima, 1946). In terms of Western culture, DMT was first synthesized by a Canadian chemist, Richard Manske, in 1931 (Manske, 1931) but was, at the time, not assessed for human pharmacological effects. Taking results from these and more classical studies of DMT biochemistry and pharmacology together, this report examines some of the past and current data in the field and proposes several new directions and experiments to ascertain the role of endogenous DMT. Recent research has stimulated a renewed interest in further study of this compound as a neuro-regulatory substance and, thus, a potential neuro-pharmacological target. With the discovery of the endogenous hallucinogen N, N-dimethyltryptamine (DMT, 1, Figure Figure1), 1), perhaps, as with the endogenous opioids, we have a similar opportunity to understand perception and consciousness. Such may also be the case for understanding perception and consciousness. We came to better understand the common human experience of pain through examining the pharmacology of administered opiates and the subsequent discovery of endogenous opioid ligands, receptors and pathways that are predominantly responsible for and regulate the experience and perception of pain. Perhaps the science behind the discovery of endogenous opioids offers us a corollary. Given their status as “psychedelics” (mind-manifesting substances), increased study of the hallucinogens, particularly with advanced brain imaging and molecular biology approaches, may provide a better understanding of the “common” biochemistry that creates mind. Nonetheless, it is conceivable that attaining an explanation for these related natural human phenomena may lie in resolving the biochemical mechanisms involved in the more dramatic pharmacology of hallucinogens, recognizing that the complexities and intensity of the “administered” experience are, essentially, an overdose relative to corresponding natural regulatory controls.
By comparison, the natural biochemical processes for our related “hallucinatory” experiences are obviously far more highly regulated, occurring as an orchestrated and inherent function of the “normal” brain. However, the experience of administered hallucinogenic substances is far more intense, robust and overwhelming than the subtlety of mere dreams. The experiences derived from the administration of hallucinogens are often compared to dream states. And it is troubling that we have not sufficiently turned the scientific method on these latter subjects despite the profound role they have played in the evolution of our science, philosophy, psychology and culture. This is also true for extraordinary states of consciousness such as “visions” or spontaneous hallucinations or phenomena such as near-death experiences (NDE). We do not understand the basic biochemical mechanisms of some of our most common experiences, such as the many human aspects of creativity, imagination or dream states. For that matter, we do not fully understand the biochemistry of perception itself or how we live such a vivid and complex internal life in the absence of external stimulation. It is the only class of compounds that efficiently and specifically does so. Despite their presence in the human pharmacopeia for millennia, we have yet to resolve the biochemical mechanisms by which the hallucinogens (psychedelics) so dramatically alter perception and consciousness.
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