Eric Stachurski

Natural Products

10-02-02

Shared Homework #3

LSD - lysergic acid diethylamide

1) Structure and structural futures

a) What is its structural and chemical formula?

b) What are its physical and chemical characteristics such as boiling point, melting point, density, refractive index, optical rotation, and solubility?

Name	Boiling point (◦C)	Melting point (◦C)	density	Refractive index	Optical rotation	Solubility
LSD - lysergic acid diethylamide	80-85	----	----	------	-------	Slightly soluble

c) What heterocyclic rings does it contain such as puridine, indole, or quinoline?

2) Source and isolation

a) What plant/organism produces the alkaloid? Where does the plant grow? Under what conditions does it grow?

One of the most commonly known plants that produces ergot is the rye (Secale cereale) To be exact the medicinal ergot is the dried sclerotium of the fangus Claviceps pupures that is being developed in the ovary of the rye itself. This parasitic fungus is also to be found in other growing kinds of cereal grasses. It appear as a blackish-purple club- shaped growth [sclerotia] on the tops of the rye where the seeds are, and are referred to as "heads of ergot"; from these heads sprout the Claviceps purpurea fungal fruiting bodies. They have long stems with bulbous heads when seen under a strong glass or microscope.

Most of the medicinal ergot is cultivated in Czech Republic, Germany, Hungary, Switzerland, Austria and Poland where the field of red rye are artificially infected with spores cultures of Clavicps purpurea.

The growth conditions: moderate climate, direct and indirect sun light, rain-fall 450-750mm annually.

b)

What part of plant or organism is the best source of the alkaloid?

The fungal fruiting bodies (“heads of ergot”) of the Claviceps purpurea.are the best sources of the alkaloids.

c) In what form is the alkaloid used?

LSD (lysergic acid diethylanine) as one of the ergot’s derivatives was discovered in 1938 by a Swiss chemist Albert Hofman. While LSD issued almost exclusively as recreational drug with practically no use in conventional medicine, it is widely abused as a hallucinogen, known as “acid”. It is the most active and specific psychotomimetic known that is a mixed agonist-antagonist at 5-HT receptors, strongly interfering with the neurotransmitter serotonin and other normal processes.

There are several forms of this particular drug known on the market. It exists in three major forms:

3) Related Alkaloids

a) What other alkaloids are in the same “family?” i.e. they are produced by the same species or they have common structural characteristics.

Naturally ergot produces a large variety of different chemical compounds known as “Ergot Alkaloids. All of these compounds have some degree of psychoactivity. Another very dangerous side effect that is being caused by the above mentioned alkaloids is vasoconstriction [narrowing of blood vessels], which, if severe, can lead to gangrene of the extremities. Most of the compounds are synthesized in the laboratories, whereas others like ergomertrine if being synthesized by a plant commonly known as a Morning Glory. Seeds are the part of the plant that contains this hallucinogenic drug used by Mexican Indians in religious and other ceremonies in order to provide a contact with gods.

b) What is a common structural characteristic of this family?

The common characteristic of this family of alkaloids is the presence of the (+)-lysergic acid.

Family of the “Ergot Alkaloids”

c) How has the alkaloid been synthetically modified of mimicked to enhance its activity?

LSD is a synthetic chemical derived from ergot alkaloids. Synthesis methods begin with tryptophan that is used in the synthesis of indole - Lysergic Acid. As of today there has been no modification of the final product LSD (D-lysergic acid diethylamide ) of such a synthesis.

3) Discovery and traditional use

a) How did the alkaloid become internationally renown?

Albert Hofmann – chemist who developed synthesis of LSD was also its promoter. After several articles about the experiences that he encountered while using small dosages of the drug it was obvious that the usage and popularity of the “new discovery” will dramatically increase. In late 1960’s compound is being widely abused as a hallucinogenic drug.

b) What is the history of its use?

1938	Albert Hofmann, a chemist working for Sandoz Pharmaceutical, synthesizes LSD-25 for the first time in Basel, Switzerland while looking for a blood stimulant. LSD research is not continued until 5 yrs later.
Apr 16, 1943	Albert Hofmann accidentally experiences a small amount of LSD for the first time. This is the first human experience with pure LSD-25. He reports seeing "an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscope like play of colors." The experience lasted just over two hours.
Apr 19, 1943	Bicycle Day - Albert Hofmann intentionally takes (250 ug) LSD for the first time. This is the first intentional us of LSD. 1
1949	Dr. Max Rinkel brings LSD to the United States from Sandoz Pharmaceuticals in Switzerland and initiates work with LSD in Boston; Nick Bercel commences LSD study in Los Angeles. 2
1951	CIA becomes aware of and begins experimenting with LSD.
1953	First LSD clinic opened to the public in England under Ronald Sandison. Separately, unwitting subjects in the United States were given LSD in the CIA funded Project MK-Ultra to test the effects of the drug.
1953	Dr. Humphrey Osmond begins treating alcoholics with LSD. 2
1955	First conferences focusing on LSD and mescaline take place in Atlantic City and Princeton, N.J.
1960	Harvard University's Timothy Leary establishes the Psychedelic Research Project.
1962	Congress passes new drug safety regulations and the FDA designates LSD an experimental drug and restricts research. The first LSD related arrests are made by the FDA. 2
1963	LSD first appears on the streets (liquid on sugar cubes). Articles about LSD first appear in mainstream media (Look, Saturday Evening Post). 2
1966	Leary founds the League of Spiritual Development, with LSD as the sacrement. 3
Mar 25, 1966	Life publishes cover article on LSD. "LSD: The Exploding Threat of the Mind Drug that Got Out of Control".
Apr 1966	Sandoz Pharmaceutical recalled the LSD it had previously distributed and withdrew its sponsorship for work with LSD. 3
Oct 6, 1966	LSD becomes illegal in California. 4
1967	LSD banned federally in the U.S.
Summer 1969	Orange sunshine acid first appears. 2
1970	An estimated 1-2 million Americans have used LSD.
Oct 27, 1970	The Comprehensive Drug Abuse Prevention and Control Act is passed. Part II of this is the Controlled Substance Act (CSA) which defines a scheduling system for drugs and places most of the known hallucinogens (LSD, psilocybin, psilocin, mescaline, peyote, cannabis, MDA) in Schedule I.
Early 1970s	LSD impregnated paper ("blotter") first hit the streets. Very quickly the paper began being printed with colorful art.
mid 1970's	Blotter paper begins to emerge as the most common form of LSD sold on the street. Previously it had been tablets and powder, but blotter and gel-tabs proved more consistent in purity and potency. 5
1979	Albert Hofmann publishes "LSD: My Problem Child." 1

c) What effects does the alkaloid have on the human body?

LSD is currently known as one of the most potent mood-changing chemicals. The effects of this drug are known to be almost unpredictable. They depend on the amount taken; the user's personality, mood, and expectations; and the surroundings in which the drug is used. The user may feel several different emotions at once or swing rapidly from one emotion to another. Sensations may seem to "cross over," giving the user the feeling of hearing colors and seeing sounds. Some LSD users experience severe, terrifying thoughts and feelings, fear of losing control, fear of insanity and death, and despair while using LSD. Some fatal accidents have occurred during states of LSD intoxication. Many LSD users experience flashbacks, recurrence of certain aspects of a person's experience, without the user having taken the drug again. A flashback occurs suddenly, often without warning, and may occur within a few days or more than a year after LSD use. Currently the LCD is known as a not addictive drug but it can lead to schizophrenia.

References:

http://165.112.78.61/Infofax/lsd.html

http://chemfinder.cambridgesoft.com/result.asp

http://www.whitehousedrugpolicy.gov/drugfact/lsd/

http://www.erowid.org/chemicals/lsd/lsd.shtml

http://www.erowid.org/psychoactives/psychoactives.shtml - interesting

http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml - synthesis of the LSD provided step by step!!! (although it requires an experienced organic chemist to produce) – the dark side of the internet.

http://leda.lycaeum.org/Chemicals/LSD.10.shtml

http://www.nida.nih.gov/Infofax/lsd.html

http://www.erowid.org/chemicals/lsd/lsd_timeline.php3 - the timeline and history