Psychedelic Research

In a paper in the latest issue of Science, Dominique Fontanilla and colleages have just reported that the psychedelic DMT acts as a regulator at the sigma-1 receptor. (Previously, research on the mechanisms of tryptamine psychedelics has focused primarily on serotonin receptors.) Among other things, they show that mice who have no sigma-1 receptor fail to show increased motor activity after DMT injection. This is fascinating for many reasons. The Sigma-1 receptor does not have a known endogenous neurotransmitter. Because DMT has been detected in human biofluids a couple times, the authors suggest DMT might be an endogenous modulator of the receptor. Whether DMT and related compounds turn out to have a significant biological role in mammals, this finding undeniably opens new vistas for understanding the mechanisms of psychedelics and may ultimately lead to novel treatments for mental illness.
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For some reason, this article by Stephen Szára only recently appeared on PubMed, despite having a 2007 publication date. It gives a brief overview of the author’s perspective on DMT research. Szára is from the first generation of psychopharmacology researchers and did key experiments on the pharmacology of psychoactive tryptamines, first in Hungary and then in the U.S. where he worked with Julius Axelrod, among others. Szára was the first to scientifically study DMT in humans.
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Jörg Daumann and colleagues have published a functional magnetic resonance imaging (fMRI) study comparing the effects of N,N-Dimethyltryptamine (DMT) and S-Ketamine on fMRI-measured neural activity and performance during an attention task. Although the main findings aren’t dramatic, this paper is noteworthy in another way: I believe it is the first publication to combine fMRI and serotonergic hallucinogen administration in humans. This makes their use of ultra-short-duration DMT impressive.
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