Synthesis and Discovery of LSD
On November 16, 1938, as part of a systematic study of lysergic acid derivatives, Hofmann synthesized lysergic acid diethylamide---the 25th compound in his series of ergot alkaloid variants, hence the laboratory designation LSD-25. The compound was initially tested on animals by Sandoz pharmacologists, who noted restlessness in the test subjects but found nothing of particular interest. LSD-25 was shelved.
Five years later, on April 16, 1943, Hofmann returned to LSD-25, driven by what he later described as "a peculiar presentiment" that the compound deserved further investigation. While re-synthesizing it, he inadvertently absorbed a minute quantity through his fingertips. That afternoon he experienced dizziness, restlessness, and a remarkable stream of vivid imagery upon closing his eyes---"an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors." Realizing the compound must be extraordinarily potent, he resolved to conduct a deliberate self-experiment.
Bicycle Day
On April 19, 1943---a date now celebrated worldwide as Bicycle Day---Hofmann ingested 250 micrograms of LSD, a dose he assumed would be a threshold amount. (He could not have known that the true threshold is roughly 20 micrograms; what he took was a strong dose.) Within 40 minutes, he noted the first effects in his laboratory journal: "slight dizziness, unrest, difficulty in concentration, visual disturbances, marked desire to laugh..."
The effects intensified rapidly. Hofmann asked his laboratory assistant, Susi Ramstein, to accompany him home. Because wartime restrictions prohibited automobiles, they made the journey by bicycle. During the ride, Hofmann's condition took on what he described as "threatening forms": objects appeared distorted, his neighbor seemed to transform into a malevolent witch, and he felt convinced he was going insane or dying. A house physician was summoned but found nothing physically abnormal beyond extremely dilated pupils. By evening the terror subsided and gave way to a profound sense of well-being and gratitude, accompanied by synesthetic perceptions: "Every sound generated a vividly changing image, with its own consistent form and color."
