Turn On, Tune In, Drop Out

October 22, 2010

Rheanna Sand


On this day in 1920, Timothy Leary was born. While his career in psychology brought him a PhD from Berkeley and a professorship at Harvard, his experiences in the world of recreational drugs brought him the most fame (not to mention a spot in John and Yoko's bed). His public experimentation with the psychedelic drug LSD made Leary a very influential figure in the counterculture revolution of the 1960's, as he urged his fellow citizens to, as the saying goes, "turn on, tune in, drop out."

Which begs the question: how could one molecule convert a perfectly respectable Harvard professor into a hippie messiah?

LSD, or lysergic acid diethylamide (now called simply "lysergide") belongs to the family of ergolines, which are secreted by fungus that grows on cereal grains. Moldy grains, in fact, are listed as a "medical explanation of bewitchment" and were a major player in the witch hunts of colonial Massachusetts in the late 1600s. People would eat moldy bread, ingest the ergolines, and start behaving… strangely.

This is because ergolines, along with phenylethylamines, like 2-CI, or the related MDMA, and tryptamines like psilocybin, the active ingredient in "magic mushrooms," all act at a similar place, at a receptor called 5HT2A. This receptor responds to serotonin, a neurotransmitter important in digestion and blood clotting, but most importantly in the brain, where it controls feelings of well-being.

The first person to synthesize LSD was Albert Hofmann, in 1938 when he was working for Sandoz Pharmaceuticals. He accidentally absorbed some through his fingertips and reported being:

"... affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away."

Since the experimental days of Hofmann and Leary, a bit more has been revealed about the action of hallucinogens like LSD. One study traced the action to a very specific place: the apical dendrites of pyramidal cells in prefrontal cortex - in other words, the top branches of triangular neurons in the very front of your brain. Because of this specific action, LSD has been touted as a treatment for depression, alcoholism, and cluster headaches, a type of migraine.

So, one molecule changed the course of a man's life, and the mindset of an entire generation. Does that mean that tinkering with a few apical dendrites is all it takes to change the world?



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