Albert Hofmann

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One of the most important practical applications of chemistry is in medicine and drugs. Without the developments of modern chemistry, we would still be ³curing´ headaches by drilling holes in skulls and performing crude operations without medical gloves! However, before the influence of modern chemistry, some primitive drugs, made primarily from plants, were used successfully. One such category that was had a role in many societies is that of the mind- or consciousness-altering drugs. In Mexico,
  One of the most important practical applications of chemistry is in medicine and drugs.Without the developments of modern chemistry, we would still be ³curing´ headaches by drillingholes in skulls and performing crude operations without medical gloves! However, before theinfluence of modern chemistry, some primitive drugs, made primarily from plants, were usedsuccessfully. One such category that was had a role in many societies is that of the mind- or consciousness-altering drugs. In Mexico, since before the Aztec civilization, psylocybemushrooms, peyote cactus and morning glory seeds were used to induce a state of alteredconsciousness. Opium has been used for centuries in the orient, cannabis has been used sinceancient times in parts of Europe, Africa and India and its use has now spread to most parts of theglobe. Other drugs, like caffeine and alcohol, have been widely used for years and continue to beso today.One of, if not the most important modern figures in the field of consciousness-alteringdrugs is undoubtedly the organic chemist Albert Hofmann. Nicknamed ³the Father of LSD´,Hofmann is best known for his work with psilocin, psilocybin, the American morning glory plant, and, of course, LSD. Hofmann was born in Switzerland in 1906, where he carried out hiswork and lived until his death earlier this year (April 29 th , 2008) at the age of 102. Before hiswork, little or nothing was known about the active ingredients in psilocybe mushrooms, themorning glory plant and the ergot fungus. He changed all of that, beginning with research onergot which led to perhaps his most important discovery: the synthesis of lysergic aciddiethylamide. LSD had enormous social implications and was researched by the CIA in the1950s before becoming a driving force in the social revolution of the sixties and seventies. It alsosparked Hofmann¶s interest in such drugs and led to his research on hallucinogenic mushroomsand morning glory.The discovery of LSD also had implications in chemistry and science in general. As themost potent psychedelic drug currently known to man, it demonstrates the possibility of intenseeffects from even tiny doses, and through its use in CIA programs and medicine, has stimulatedinterest in the chemical functioning of the brain and central nervous system, as well as thechemistry of psychedelic drugs. Earlier research showed indications that it could be used as a powerful tool in psychiatric therapy because of its ability to bring up and facilitate expression of repressed memories or feelings. However, it has been misused both scientifically and  recreationally, and unfortunately, it has not been explored fully as its current status as an illegaldrug in most countries inhibits serious modern research.The magnitude of its effect on science and society, and its unexplored potential, make itan important development in modern chemistry and have made its ³father´, Albert Hofmann, animportant figure, not only in chemistry, but also in the psychedelic subculture spawned in thesixties as a (partial) result of his discovery.Before Hofmann, little official research had been done on the mechanisms and possibleuses of known psychedelics and hallucinogens. Of course, these substances had long had a placein hundreds of societies since the beginning of recorded history, but their chemistry, their ³how¶s´ and ³why¶s´, had been little explored. This was simply not an active area of scientificresearch, and indeed when Hofmann began his studies on ergot, the synthesis of the most powerful hallucinogenic drug in history was nowhere in his plans.Ergot is a fungus that grows on rye and was the subject of much interest because of itsstrange effects on the mind and the body. In the middle ages it was the cause of ergot poisoning,or ergotism, which brought on epidemics of madness that affected whole villages throughout theMiddle Ages and, less frequently, in more recent times. These bouts of madness were also oftenaccompanied by St Anthony¶s Fire, a gangrenous blackening of the fingers and toes caused bysevere vasoconstriction that led to tissue damage of the extremities. It is also thought to havecaused miscarriages in pregnant women who were exposed to it. These ³epidemics´ usuallyoccurred after a wet summer had caused the growth of the fungus on rye, which was then groundinto flour to make bread. Ergotism is one of the theories for the strange behaviour that resulted inthe Salem witch hunt. The first known incidence of ergot use for a medicinal purpose was in the16 th century. Ergot is an ecbolic, meaning it promotes uterine contractions (which would explainthe miscarriages by pregnant women with ergot poisoning), and it was used by midwives anddoctors up until the 18 th century. Dosage was hard to regulate though, due to variations in theconcentration of active ingredients in a given sample of ergot, and it was abandoned because itwould lead to uterine spasms if the dosage was too high. Some doctors continued to use it to stop bleeding after childbirth but it wasn¶t until its first active ingredient was isolated that it came intowidespread use.  This active ingredient turned out to be ergotamine, isolated by Professor Arthur Stoll in1918. It was used to stop post-partum bleeding and as a treatment for migraines, but despite itssuccess, professor Stoll did not continue to work on the other possible active ingredients in ergot.Professor Stoll worked at Sandoz Laboratories in Switzerland at the time and would becomeHofmann¶s supervisor when he started there in 1929. Not long after he began, Hofmannexpressed an interest in continuing Stoll¶s work on ergot and his request was approved.When Hofmann first undertook his research on ergot, hisgoal was to determine its active ingredients and explore their  possible medicinal uses. It had been determined in the early1930s, by W. A. Jacobs and L. C. Craig of the Rockefeller Institute of New York, that all ergot alkaloids have a commonnucleus, which was named lysergic acid (molecular structure infigure 1). Following this discovery was the isolation of ergobasine (molecular structure in figure 2), an importantdevelopment in medicine because of its effectiveness as auterotonic (gives tone to the smooth muscle of the uterus) and ahaemostatic (stops bleeding). Through the process of chemicaldegradation, Jacobs and Craig found that the constituents of thisalkaloid were lysergic acid and the amino acid popanolamine.By looking at the molecular structures, the similarity betweenergobasine and lysergic acid is immediately apparent. Hofmanndecided to try to work the process backwards and synthesizeergobasine from lysergic acid and propanolamine. The first successful synthesis of ergobasinewas important because it enabled more efficient production than the isolation from ergot. It alsohelped verify the chemical structure of ergobasine. From there, Hofmann continued his researchwith ergobasine, substituting different amino alcohols in the place of propanolamine. This lead tothe discovery of an even more effective form of ergobasine, synthesized from lysergic acid and butanolamine.Hofmann also continued his research on another front: synthesizing other lysergic acidcompounds in the search for new pharmaceutical products. He began going through its  derivatives and in 1938 he first synthesized what would becomeknown on the street as acid. He called it lysergic acid diethylamide,or LSD-25 for short, because it was the 25 th derivative to besynthesized. He expected it to have respiratory and circulatorystimulation effects because of its structure (shown in figure 3), butwhen it was sent to the pharmacological department for testing, theresults were disappointing. In some tests done on mice, it appearedto make them restless, but none of the expected therapeutic effectswere observed. It was discarded and Hofmann moved on to other research involving compoundsin ergot.It was not until five years later, in the spring of 1943, that Hofmann would return to work on LSD-25. Hofmann decided to take another look at the compound after apparently having felta strong premonition about it, a feeling that perhaps he missed something the first time around.He set out to produce another sample of the compound for testing by the pharmacologicaldepartment. What happened next was, and still is, somewhat of a mystery. It was believed by Dr.Hofmann that he absorbed a small amount of LSD through his fingers while working with thecompound. He soon began to feel a strange sensation of restlessness and anxiety, and had toleave the lab to go home and rest. He was experiencing the first ³acid trip´ in history (albeitmild), and the effects he felt, such as some mild visual distortions and mood swings, confirmedhis earlier premonition about LSD.A few days later, on April 19 th , 1943, he had his first intentional experience with LSD.He had some trouble determining dosage, as he knew the substance must be extremely potent tohave produced such significant effects from the small amount that would have been absorbedthrough his skin. He based his decision on the potency of other ergot alkaloids and took a dose of 250 µg. Considering that common modern recreational doses range from 50 ± 150 µg, one cangain some insight into the intensity of his experience. Not long after having taken the LSD at the lab, Hofmann decided that he needed to gohome, and asked his laboratory assistant to accompany him. As they rode home on their bicycles,Hofmann began to experience the intense effects of the drug. His condition worsened when hegot home, and he experienced fairly extreme visual disturbances, such as the faces of those
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