Catalyzing Solutions: the Chemistry of Psychedelics

By JOSE MONGE CASTRO

When our team first started working on “Catalyzing Solutions,” I thought: “Wouldn’t it be crazy if we talked about drugs in The Catalyst?” And well, since this is an independent publication and Llamapalooza is tomorrow, here we are. But before you get too excited, this is also not a how-to on homemade DMT. 

Naturally occurring and ubiquitous in nature, mind-altering substances have been used by cultures around the world for millennia. Often used as entheogens (substances with a religious/spiritual dimension), substances with this label have only recently entered the body of common western knowledge. 

From atomic bombs to the no less explosive but much less insidious quasi-magical discovery of lysergic acid diethylamide (LSD) in 1943, the last century witnessed unparalleled progress in all fields of science. With works such as the mycology-driven R. Wasson’s account of “magic mushrooms” to the more intentional work of Alexander Shuling, “psychedelic drugs” have followed a most dramatic arc. From “miracle drugs,” praised by avant-garde psychiatrists, to underground sacraments to sources of moral panic, many of these compounds made it from labs to schedule I in record time. 

Image Courtesy of David E. Nichols, PhD.

At the same time, neuroscience had recently discovered the role and structure of neurotransmitters; and that is exactly where the “magic” from these substances come from. For the most part, psychedelics are chemically simple compounds, no more complex than aspirin. 

Psychedelics are often synthesized by plants with natural chemical roles yet to be understood. Dozens of these compounds, mainly alkaloids (nitrogen-containing organic molecules), have been isolated. Psilocybin, mescaline (a now illegal cactus), and muscimol are some examples that, with small changes, can be transformed into new compounds with additional properties. Particularly important is their structure similarity with neurotransmitters, which explains why these substances are easily accepted by the brain: they have almost identical binding sites, similar pKas, and charges which translate into already-existing metabolic pathways. 

It is therefore understandable why compounds of this sort pose an opportunity to study and develop drugs to aid with brain-imbalances in cases of depression, addiction, anxiety, and trauma. Although research in this area has recently seen some progress after a hiatus on the second part of the century — most notably with the work done at John Hopkins University on Psilocybin — the legal and moral frameworks are not yet conducive to seeing potentially lifesaving medicines become a reality.  

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