Can LSD be kept green on its clinical path?



A glorious bike ride can be found floating on the front pages of LSD’s history. Underneath the immediate front page is the context of wartime experiments, and chemical and psychological weapons. As judgement surrounding LSD finally evolves back into peaceful experimentations, should we steer the hallucinogen down a green path towards its clinical future?

Psychedelics are a multiplex of various industries each with different nuances. Two denominators are hanging in the balance to be mindful of — money and the pharmaceutical giants banking on anti-depressants. Pharma has fought against many psychedelics for decades, only recently upturning any corporate strategies to accept their hallucinogenic competition. As microdosing grows common across cultures, can LSD be kept green on its clinical path without becoming obtusely pharmaceutical?

History of rye and LSD

Some substances have been with humans long enough that our documents are within fossil records or ancient text. Caffeine pills sold over the counter at a pharmacy instead of the tradition of brewed coffee? Whereas LSD, as the famously active chemical, is not even a century old. Lysergic acid stirred down from alkaloids derived from a fungus, and chemically affixed with a diethylamide group, first appeared artificially on November 16, 1938.

Human consumption of ergot-containing substances on another hand is rich in our history. Old rye bread eaten amongst impoverished citizens caused mass poisoning during the Middle Ages. Yet, by 1582, the medicinal properties of ergot were documented.

LSD is derived from ergot and was intended as a clinical heart medication.
Claviceps purpurea grows on rye, for example and produces a conical shaped spore (sclerotium) known as ergot.

A diethylamide group for failed clinical heart medicine, LSD

Albert Hofmann never intended to create a molecule that was so potent by combining ergotamine with different indole groups. Rather, Hofmann was working as a chemist on alkaloids derived from ergot, a spore found in a fungus that grows on rye. Research in the 1930s was intended to continue work conducted by Arthur Stroll in 1917. Stroll was the first to isolate pure ergotamine alkaloids, whereas W.A. Jacobs and L.C. Craig first elucidated the chemical structure of lysergic acid in 1934.

Nicotinic acid diethylamide was a cardiovascular drug under the name, Coramine. After lunch during his work with ergot alkaloids in 1938, Hofmann decided to build a similar compound using lysergic acid. His goal was to create a likewise cardiovascular drug.

In its final form then, LSD was designed to be a medicine, but derived from nature. In essence, however, LSD failed as a pharmaceutical. Preclinical tests on animals would never have determined the new compounds’ endless potential. That potential remained hidden until an accidental chemical exposure forced Hofmann to evacuate his lab one day via a euphoric bicycle ride back home.

Considering past failures, should pharmaceutical industries be allowed to rake in any green on mental health therapies with LSD?

Fully synthetic LSD is more viable for clinical applications, regardless its less than green origins.

A chemical fork in the road

Chemists are often presented with choices when synthesizing molecules. Different methodologies can lead to the synthesis of the same molecule. In the case of LSD, one can start with lysergic acid from ergot, slowly extracting the alkaloids into a viable filter cake.

Otherwise, skipping a few reagants and hours of magnetic stirring, lysergic acid can be produced from synthetic ergotamine. Based on substances in ergot, the second method employs full chemical synthesis and saves on the use of natural fungus. We established the benefits and potential impacts synthetic MDMA has on the environment. What about different psychedelics? Should chemists take a green or synthetic path while producing LSD for a complex and clinical industry?

Let us know in the comments what you think about the future of LSD in any clinical space?

Sources

  1. Hagenbach, D. and Werthmuller, L. 2013. Turn On, Tune In, Drop Out–and Accidentally Discover LSD [Excerpt]. Scientific American. Accessed: April 19, 2022.





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