April 19, 1943

“Everything in my field of vision wavered and was distorted as if seen in a curved mirror.”

Albert Hofmann's laboratory journal for April 19, 1943 holds three short entries. In his later account of that day he says the notes end there, and that he managed the last words only with great effort.

Hofmann was a chemist at a Basel drug company, working on ergot alkaloids. In 1938 he had made the twenty-fifth compound in a series of lysergic acid derivatives, LSD-25, hoping for a circulatory and respiratory stimulant. The pharmacologists recorded a strong effect on the uterus and noted that the test animals grew restless, but they showed no special interest, and testing stopped. Five years later, in the spring of 1943, a hunch that the substance might have properties the first tests had missed led him to make it again.

On Friday, April 16, in the middle of the afternoon, he had to stop work. He felt restless and slightly dizzy, went home and lay down. In the report he sent to Professor Stoll at the company, he described an "uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors." The state faded after about two hours. He suspected that a trace of the solution had touched his fingertips during crystallization and been absorbed through the skin.

Three days later, on Monday, April 19, Hofmann decided to test that guess with a deliberate self-experiment. The date is now marked by enthusiasts as Bicycle Day. He chose what he believed was the smallest amount that could produce any effect, judging by what was then known about ergot alkaloids, and took it at 4:20 in the afternoon, diluted in water. It proved too much. The volunteers Werner Stoll tested in Zurich a few years later received substantially less, and Hofmann himself wrote that the grave side effects of his session came from overdosage.

Forty minutes later his journal records "dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh." A supplement dated April 21 adds that he went home by bicycle and that the worst of the crisis ran from six to about eight that evening. He asked his laboratory assistant to escort him, and with no automobile available because of wartime restrictions, they rode. His field of vision wavered as if seen in a curved mirror. He felt unable to move from the spot, although the assistant told him afterward that they had traveled very fast.

At home he could barely ask his companion to summon the family doctor and to ask the neighbors for milk, which he chose as a general antidote for poisoning. The neighbor who brought it was, to him, "a malevolent, insidious witch with a colored mask." He feared he was going insane. He asked himself, "Was I dying?"

By the time the doctor arrived, the worst had passed. The doctor found extremely dilated pupils and nothing else abnormal. Pulse, blood pressure and breathing were normal. Slowly the terror gave way, and Hofmann began to watch the colors and shapes behind his closed eyes. This was the first documented deliberate LSD experience, and for several hours it was frightening.

He slept, and woke refreshed. Walking in the garden after a spring rain, he wrote, "everything glistened and sparkled in a fresh light. The world was as if newly created."

Hofmann could only guess at the mechanism. After serotonin was identified in the brain, early researchers suspected that LSD acted through it. David Nichols's 2016 review in Pharmacological Reviews reports a consensus that psychedelics act as agonists or partial agonists at the serotonin 5-HT2A receptor, with particular importance for receptors on pyramidal cells in layer V of the cortex. In a 2018 study, Preller and colleagues gave LSD to 24 healthy volunteers. It changed connectivity across the brain, including the thalamus, and a drug that blocks the 5-HT2A receptor fully blocked those effects. Huxley, writing in 1954 about mescaline, described the brain as a "reducing valve" that filters what reaches awareness, borrowing the image from C. D. Broad's reading of Bergson. The thalamus findings can be read as consistent with that picture. That reading is an interpretation, and the picture remains a metaphor.

Hofmann lived to 102 and died in 2008. He named his memoir LSD: My Problem Child, and in it he describes how his joy at having fathered the compound was tarnished when it spread as an inebriant. He asked himself, "Would LSD become a blessing for humanity, or a curse?"

Werner Stoll published the first scientific description of its effects in 1947, in a Swiss neurology and psychiatry journal. Psychiatrists in Switzerland, Germany, Britain, Czechoslovakia and the United States then used it in therapy. Lester Grinspoon wrote in 1981 that between 1950 and the mid-1960s more than a thousand clinical papers discussed 40,000 patients, with problems that included alcoholism and obsessional neurosis. Hofmann also describes its use with dying patients. The 40,000 figure is a retrospective count, and the evidence is uneven. A 2012 meta-analysis by Krebs and Johansen pooled six randomized trials of LSD for alcoholism, with 536 participants, and found a beneficial effect on alcohol misuse.

The law closed in during the 1960s. On August 23, 1965, the company announced it would stop producing and distributing LSD, citing misconceptions spread by publicity, the absence of adequate legislation, and wider availability after the last patent expired in 1963. Licensed researchers could still obtain it by special permit, and Hofmann wrote that the paperwork discouraged many of them. Public Law 90-639, signed on October 24, 1968, raised the penalties for unlawful acts involving LSD and extended the federal possession offense to it. The Controlled Substances Act of 1970 later placed it in Schedule I, a category defined by high potential for abuse and no currently accepted medical use in treatment in the United States. Grinspoon attributed the end of most clinical work to legal and financial obstacles as much as to any loss of interest.

Hofmann lived to see human research with psychedelics resume. Strassman and Qualls published dose-response studies of DMT in 1994, and a Johns Hopkins group led by Griffiths published a psilocybin study in 2006. A Swiss pilot study of LSD-assisted psychotherapy, by Gasser and colleagues, appeared in 2014, six years after his death.

The journal stops after those few lines. The literature that followed has now run for more than eight decades.

Sources

• Hofmann, LSD: My Problem Child (1979)
• Nichols, D.E. Psychedelics. Pharmacological Reviews, 68(2):264-355 (2016)
• Preller et al., Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor, eLife (2018)
• Huxley, The Doors of Perception (1954)
• Grinspoon, L. LSD Reconsidered: Should clinical research be resumed? The Sciences (January 1981)
• Krebs & Johansen, Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials, J Psychopharmacol (2012)
• Public Law 90-639, 82 Stat. 1361 (October 24, 1968)
• Controlled Substances Act, 21 U.S.C. 812 (1970); 21 CFR 1308.11
• Strassman & Qualls, Dose-response study of N,N-dimethyltryptamine in humans I, Arch Gen Psychiatry (1994)
• Griffiths et al., Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance, Psychopharmacology (2006)
• Gasser et al., Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases, J Nerv Ment Dis (2014)
• Albert Hofmann (1906 to 2008), University of Zurich Department of Chemistry symposium page