University of Belgrade

Faculty of Chemistry

LSD

Mentor Pavelka iri

Student Stefan Golubovi HE03/2012

Lysergic acid diethylamide (molecular formula C20H25N2O), abbreviated LSD or LSD25, also known as lysergide (INN) and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synesthesia, an altered sense of time and spiritual experiences, as well as for its key role in 1960s counterculture. It is used mainly as an entheogen, recreational drug, and as an agent in psychedelic therapy. LSD is non-addictive, is not known to cause brain damage, and has extremely low toxicity relative to dose. However, adverse psychiatric reactions such as anxiety, paranoia, and delusions are possible. LSD was first synthesized by Albert Hofmann in 1938 from ergotamine, a chemical derived by Arthur Stoll from ergot, a grain fungus that typically grows on rye. The short form "LSD" comes from its early code name LSD-25, which is an abbreviation for the German "Lysergsure-diethylamid" followed by a sequential number. LSD is sensitive to oxygen, ultraviolet light, and chlorine, especially in solution, though its potency may last for years if it is stored away from light and moisture at low temperature. In pure form it is a colorless, odorless, tasteless solid. LSD is typically delivered orally, usually on a substrate such as absorbent blotter paper, a sugar cube, or gelatin. In its liquid form, it can also be administered by intramuscular or intravenous injection. LSD is very potent, with 2030 g (micrograms) being the threshold dose. New clinical LSD experiments in humans started in 2009 for the first time in 40 years. IUPAC name of LSD is (6aR,9R)- N,N- diethyl- 7-methyl- 4,6,6a,7,8,9- hexahydroindolo[4,3-fg] quinoline- 9-carboxamide. Half-life of LSD is 35 hours. Routes of administration in human body are oral, intravenous, ocular, intramuscular. Molecular mass of LSD is 323,43 g/mol, its melting point is at 8085 C (176185 F).

Structure LSD is a chiral compound with two stereocenters at the carbon atoms C-5 and C-8, so that theoretically four different optical isomers of LSD could exist. LSD, also called (+)-D-LSD, has the absolute configuration (5R,8R). The C-5 isomers of lysergamides do not exist in nature and are not formed during the synthesis from D-lysergic acid. Retrosynthetically, the C-5 stereocenter could be analysed as having the same configuration of the alpha carbon of the naturally occurring amino acid L-tryptophan, the precursor to all biosynthetic ergoline compounds.

However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of bases, as the alpha proton is acidic and can be deprotonated and reprotonated. Non-psychoactive iso-LSD which has formed during the synthesis can be separated by chromatography and can be isomerized to LSD. A totally pure salt of LSD will emit small flashes of white light when shaken in the dark. LSD is strongly fluorescent and will glow bluish-white under UV light.

Synthesis LSD is an ergoline derivative. It is commonly synthesised by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride and peptide coupling reagents. Lysergic acid is made by alkaline hydrolysis of lysergamides like ergotamine, a substance usually derived from the ergot fungus on agar plate, or theoretically possible, but impractical and uncommon from ergine (lysergic acid amide, LSA) extracted from morning glory seeds. LSD (lysergic acid diethylamide) is one of the major drugs making up the hallucinogen class. LSD was discovered in 1938 and is one of the most potent mood-changing chemicals. It is manufactured from lysergic acid, which is found in ergot, a fungus that grows on rye and other grains. LSD, commonly referred to as "acid", is sold on the street in tablets, capsules, and, occasionally, liquid form. It is odorless, colorless, and has a slightly bitter taste and is usually taken by mouth. Often LSD is added to absorbent paper, such as blotter paper, and divided into small decorated squares, with each square representing one dose. The Drug Enforcement Administration reports that the strength of LSD samples obtained currently from illicit sources ranges from 20 to 80 micrograms of LSD per dose. This is considerably less than the levels reported during the 1960s and early 1970s, when the dosage ranged from 100 to 200 micrograms, or higher, per unit.

Health Hazards The effects of LSD are unpredictable. They depend on the amount taken; the user's personality, mood, and expectations; and the surroundings in which the drug is used. Usually, the user feels the first effects of the drug 30 to 90 minutes after taking it. The physical effects include dilated pupils, higher body temperature, increased heart rate and blood pressure, sweating, loss of appetite, sleeplessness, dry mouth, and tremors. Sensations and feelings change much more dramatically than the physical signs. The user may feel several different emotions at once or swing rapidly from one emotion to another. If

taken in a large enough dose, the drug produces delusions and visual hallucinations. The user's sense of time and self changes. Sensations may seem to "cross over," giving the user the feeling of hearing colors and seeing sounds. These changes can be frightening and can cause panic. Users refer to their experience with LSD as a "trip" and to acute adverse reactions as a "bad trip." These experiences are long - typically they begin to clear after about 12 hours. 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. LSD is usually sold in tablets or capsules, but sometimes in liquid form. The liquid is sometimes applied to absorbant paper, called "window pane" or "blotter" acid, which is cut up into individual doses. When this system is disrupted by taking LSD, it can cause profound distortions in the user's perception of reality, or in other words, hallucinations. LSD users see images, hear sounds and feel sensations that seem to be very real, but they are not real at all. These sensory hallucinations can be accompanied by rapid and intense emotional swings. Consequently, an LSD "trip" can go from being a pleasant experience to a very unpleasant one very quickly, making the effect of the drug extremely unpredictable.

The Effects of LSD Some of the most dramatic effects of LSD reported by researchers in smaller or case studies include:

Dramatic changes in sensations and feelings.

Feeling several different emotions at once.

Swing rapidly from one emotion to another.

Altered sense of time. Altered sense of self. Crossover senses, synesthesia (hearing colors, seeing sound)

These altered perceptions and sensations can cause panic in LSD users. Some experience terrifying thoughts, feelings of despair, fear of losing control, fear of insanity and fear of death. These experiences are what is known as having a "bad trip." Scientists have also not been able to explain why some LSD users have flashbacks - a sudden recurrence of aspects an LSD trip without warning. These flashbacks can happen within a few days of the original use of the drug or sometimes more than a year later. The problem for LSD users is that all of these effects, pleasant or unpleasant, are unpredictable. The same dose of the same batch of LSD can affect one person completely differently from another person. Moreover, a user can be affected differently from one trip to the next taking the same amount and same kind of LSD. You never know when you might have a bad trip. Fortunately, LSD is not addictive and most users eventually get tired of it and simply quit voluntarily, or decrease their use over time. However, users can build up a tolerance to the drug, requiring them to take higher amounts to achieve the same state the previously achieved, which can be dangerous due to the unpredictability of the drug. The precise mechanism by which LSD alters perceptions is still unclear. Evidence from laboratory studies suggests that LSD, like hallucinogenic plants, acts on certain groups of serotonin receptors designated the 5-HT2 receptors, and that its effects are most prominent in two brain regions: One is the cerebral cortex, an area involved in mood, cognition, and perception; the other is the locus ceruleus, which receives sensory signals from all areas of the body and has been described as the brain's "novelty detector" for important external stimuli.

Why do people take hallucinogenes? Hallucinogenic drugs have played a role in human life for thousands of years. Cultures from the tropics to the arctic have used plants to induce states of detachment from reality and to precipitate "visions" thought to provide mystical insight. These plants contain chemical compounds, such as mescaline, psilocybin, and ibogaine, that are structurally similar to serotonin, and they produce their effects by disrupting normal functioning of the serotonin system. Historically, hallucinogenic plants were used largely for social and religious ritual, and their availability was limited by the climate and soil conditions they require. After the development of LSD, a synthetic compound that can be manufactured anywhere, abuse of hallucinogens became more widespread, and from the 1960s it increased dramatically. All LSD manufactured in this country is intended for illegal use, since LSD has no accepted medical use in the United States.

References
1. Papac, DI; Foltz, RL (May/June 1990). "Measurement of lysergic acid diethylamide (LSD) in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry" (PDF). Journal of Analytical Toxicology 14 (3): 189190. 2. The Good Drugs Guide. "LSD psychedelic effects". 3. Buckholtz, NS; Zhou, DF; Freedman, DX; Potter, WZ (1990). "Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain". Neuropsychopharmacology 3 (2): 137148. 4. Alexander and Ann Shulgin. "LSD", in TiHKAL (Berkeley: Transform Press, 1997). 5. Monte AP, Marona-Lewicka D, Kanthasamy A, Sanders-Bush E, Nichols DE (March 1995). "Stereoselective LSD-like activity in a series of d-lysergic acid amides of (R)- and (S)-2-aminoalkanes". J. Med. Chem. 38 (6): 95866. 6. Nichols DE, Frescas S, Marona-Lewicka D, Kurrasch-Orbaugh DM (September 2002). "Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD)". J. Med. Chem. 45 (19): 43449.