270 KOPIN
of tuberculosis. The patients became euphoric, had boundless energies,
but their X-rays did not improve. Nathan Kline called this drug a “psychic
energizer” and suggested that it be used for the treatment of depression.
The results were so encouraging that by 1957 or 1958, hundreds of thou
sands of depressed patients were beginning to take this MAO inhibitor.
Iproniazid was withdrawn from the market because of toxic side effects,
but other less toxic MAO inhibitors were found and came into wide
use. The efficacy of these drugs provided a strong argument for linking
to amines to mental illlness.
Another link to amines resulted from the introduction of reserpine.
For many centuries, the root of Rauwolfia serpentina, snakeroot plant,
was used for treating snake bites, but it also was used for treating anxiety,
insomnia, and “general insanity.” In 1948, reserpine was isolated from
this source and CIBA put this drug on the market. It was first used as a
sedative and an antihypertensive agent, but its use declined when it was
found to induce depression. When it was discovered that reserpine was
a powerful means for depleting brain amines (serotonin and catechola
mines), another link of amines to brain function was established.
Also, in the 1950s, psychedelic agents were popularized by the
publication in 1954 of Aldous Huxley’s The Doors of Perception. The
hallucinogenic effects of agents such as mescaline or lysergic acid
diethylamide (LSD) were described as “mind expanders.” Mescaline was
the most active of the components of peyote, a cactus plant that had
been used in Mexico for centuries to induce a hallucinogenic, “mystic”
state. LSD, a derivative of ergot, was accidentally discovered to be an
hallucinogen in 1943 by Albert Hofmann in Switzerland, He had been
working on drugs related to ergot alkaloids that might be useful for
treatment of migraine headaches and had synthesized LSD. Infinitesimal
amounts of this material cause hallucinations and when Hofmann
inadvertently ingested or inhaled the chemical, he became sick and
developed hallucinations. Because the hallucinations were recognized
as similar to those experienced by schizophrenic patients, many investi
gators throughout the world, including at the NIH, began to study the
effects of LSD.