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Lysergide
LSD
The discovery of lysergide came after the isolation of ergot alkaloids grown of fungus on the rye and other cereal plants. The fungus Claviceps purpurea which infects rye and other cereal grains, it produces ergotism, an illness in people who eat bread made from infected grains.
LSD is a hallucinogenic substance produced from lysergic acid, a substance derived from the ergot fungus (Claviceps
purpurea) which grows on rye. LSD can also be derived from lysergic acid amide which is
found in morning glory seeds. LSD is also referred to as LSD-25 because it was the twenty-
fifth in a series of compounds produced by Dr. Albert Hofmann in Basel, Switzerland.
Morning glory (Ipomoea purpurea)
LSD is the most potent hallucinogenic substance known. Dosages of LSD are measured in micrograms (one microgram
equals one/one millionth of a gram). LSD is available in the form of very small tablets (“microdots”), thin squares of
gelatin (“window panes”), or impregnated on blotter paper (“blotter acid”). The most popular of these forms in the 1990s is blotter paper perforated into 1/4 inch squares. This paper is
usually brightly colored with psychedelic designs or lines.
Because of its high potential for abuse and no accepted medical use, it is classified as a schedule I substance (1471 convention on psychotropic substances)
Effects of LSD on the Nervous System
LSD is water soluble, odorless, colorless and tasteless - it is a very powerful drug - a dose as small as a single grain of salt (about 0.010 mg) can produce some effects. Psychedelic
effects are produced at higher doses of about 0.050-0.500 mg.
The effects of LSD depend on a user's mood and expectations of what the drug will do
and last several hours. The behavioral effects that LSD can produce include:
• Feelings of "strangeness" • Vivid colors • Hallucinations • Confusion, panic, psychosis, anxiety • Emotional reactions like fear, happiness or sadness • Distortion of the senses and of time and space • "Flashback" reactions - these are the effects of LSD
that occur even after the user has not taken LSD for months or even years.
• Increases in heart rate and blood pressure • Dilatation of the pupil• Chills • Muscle weakness
Tolerance to the effects of LSD develops quickly and users must increase their intake of LSD to get the same effects. The exact neural pathways that
are affected by LSD are not completely known.
LSD has a chemical structure that is very similar to the neurotransmitter called serotonin. It is thought that the effects of LSD are caused by
stimulation of serotonin receptors on neurons, perhaps in the brain area called the raphe nuclei. However, it is still not clear what produces all the
effects of LSD.
It is the most potent of all known hallucinogenic substances, the first produced and perhaps the best known of synthetic hallucinogens.
Chemically, lysergide is the d-lysergic acid diethyl amide (LSD). Or N,N-diethyl-d-lysergamide.
Pharmacology and mode of action:
Lysergide like most of the hallucinogens is almost always administered orally.
Because it is so potent, only tiny amount of lysergide (several doses can be placed on the head of a pin) need to be ingested to produce psychedelic effects (variety of psychological changes produced by hallucinogenic drugs).
It is rapidly absorbed from GIT and then distributed throughout the body.
Lysergide is similar in structure to neurotransmitter serotonin and produces psychedelic effects by interfering with the normal activity of this neurotransmitter.
It is metabolized in the liver to inactive compound 2-oxy-lysergic acid diethylamide and excreted. The half-life time (????) in the blood is about three hours. Its effects last an average of 6-9 hours but can last up to 12 hours.
The physiological changes include dilated pupils, increase temperature, increase heart rate, increase blood pressure and an elevation in blood glucose level.
Sometimes the users will also be suffered, sweating and chills, dry mouth, or excessive salivation, headache, nausea and vomiting.
These effects are usually midland short term and the user’s attention is soon directed to psychological effects.
It occurs 40 minutes after these physiological effects.
It produces mood changes, abnormal perceptions of color, space and time.
Lysergide experiences may be positive (expansive) or negative (constrictive) depends on one’s mind-set and the social setting in which the drug is taken.
•Positive sensation includes feeling of creativity, deep understanding of self and universe, and feeling of grandeur.
•Negative feelings, collectively referred to as bad trip include fear, feeling of persecutions and paranoia
•Bad trips sometimes caused by other material such as phencyclidine (PCP) that were sold to user as lysergide.
•Careful studies of these using lysergide under experimental and therapeutic conditions have revealed that serious negative reactions, such as attempted suicide, are very infrequency.
•The margin for safety between effective and toxic doses is extremely high, there has never been documented overdose death from lysergide.
•The death occurs as a result of abnormal behavior after taking lysergide.
Illicit production:
Lysergide can be produced by several different methods.
The majority of which use lysergic acid as starting material.
Lysergic acid itself is produced in clandestine using either ergometerine or ergotamine tartarate as starting material.
lysergic acid+
lithium hydroxide
lithium lyserg. complex
sulfur-trioxide- DMF
diethyl aminelysergide productA-
B- Lysergic acid +N,N-carbonyl diimidazoleDiethylamine
lysergide
C- Lysergic acid+ trifluro acetic anhydridediethylamine
lysergide
•From lysergic acid:
•From Ergot alkaloids:
Ergot alkaloidhydrazine
hydratelysergic acid hydrazide
sodium nitrite Azidediethylamine
lysergide
All above methods produce products which contain large amount of isolysergic acid and other by-products as
lysergic acid, ergotamine, ergometerine and lysergic acid monoethyl amide.
Synthesis of Lysergic Acid:a) The most common method used for producing of lysergic acid in clandestine lab. is the conversion of ergotamine or ergometerine tartarate to lysergic acid
•Lysergic acid can also be produced by fermentation of cultures of Claviceps clavatus or through multistep process beginning with methyl-6-methyl nicotinate.
Illicit products:•The illicit market in 1960’s was common to apply it to a variety of substances by adding a drop of a lysergide solution to an adsorbent.
- LSD is produced in crystalline form and then mixed with excipients, or diluted as a liquid for production.
LSD is sold in tablet form (usually small tablets known as Microdots), on Sugar Cubes, in thin squares of gelatin (commonly referred to as Window Panes= in which the lysergide was incorporated into a gelatin matrix and the solidified gelatin cut into small squares), and most commonly, as blotter paper (sheets of absorbent paper soaked in or impregnated with LSD, covered with colorful designs and perforated into one-quarter inch square (individual dose units).
The content of the tablet was extremely variable, ranging from 20-500 µg of lysergide due to difficulty of obtaining a homogenous powder for tableting.
One of predominant types of tablet in particular the microdot, become prevalent in 1970’s.
•Microdots are round tablets approximately 1.6 mm in diameter and containing a reasonably uniform dose of 100 µg/tablet.
• In 1980’s, paper dosage forms became much more common. However unlike earlier paper forms, where the lysergide was dropped onto the paper and which are still used in several countries, the new paper dosage forms are produced by soaking preprinted paper, as stamps and stickers, in a solution of lysergide, thereby ensuring a more uniform product.
• Typically these sheets are perforated into squares of approximately 5 mm2 each containing a typical dose of 30-50 µg of lysergide.
Extraction of LSD Prior to Analysis
The extraction can simply be achieved by mixing the test sample for 30 s with sufficient methanol. Alternatively, a methanol/water (1:1) mixture has been reported to extract the LSD more efficiently .
If quantitative analyses are to be carried out, it is necessary to completely extract the LSD from the paper. This can be achieved by suspending the material in a large volume (15 ml is suggested) of 1% tartaric acid solution in a separatory funnel. The mixture is extracted three times with an equal volume of chloroform and then the aqueous layer is basified with 1 M NaHCO3. The resulting mixture should be extracted, three times, with an equal volume of chloroform, and the chloroform extracts combined, filtered or centrifuged, and evaporated under a stream of nitrogen.
Presumptive Tests: Due to high potency of lysergide, Care must be taken during all stages of analysis from handling of the sample when it is received to the final storage of the material after analysis.
•Many ergot alkaloids, many of which are legally used as pharmaceutical products and not subject to national or international control, will give similar results with these tests.
Fluorescence Test:
Examine the original sample dosage form under UV light at 366 nm, or alternatively, place a drop of its methanolic extract onto filter paper, dry and observe the spot again.
In both cases, the presence of lysergide is indicated by a blue fluorescence the detection limit of this method is less than 1 µg.
The negative control (methanol alone) demonstrates that the fluorescence, if observed, is due to the drug extracted into the methanol.
The positive control (methanolic solution of LSD) provides a reference colour reaction and gives an idea of the intensity of the fluorescence that might be observed.
Color Tests:
small amount of suspected material or its methanolic solution
blue to purple color indicates the presence of lysergideReagent Ehrlich R (P-DMAB/MeOH/ or thiophosphoric acid
Reagent Ehrlich = 1 g of the reagent ( p-dimethylaminobenzaldehyde) is dissolved in 10 ml of orthophosphoric acid.
Chromatographic analysis:Extraction Procedure:
•For qualitative analysis (TLC): mix test sample with alcohol Filter
•For quantitative determination (GLC, HPLC)
Sample+ 15 ml of 1% tartaric acid extract of non alkaloidal by CHCl3
neutralize with NaHCO3 Extract CHCl3
This acid-base extraction procedure is suitable for removal of lysergide impurities, but isolysergic cannot separate from lysergide by this method.
TLC: TLC with lysergide as standard solution system CHCl3: MeOH (90:10).
Visualization by physical method (UV at 254 (dark spot) and 366 nm (Blue fluorescence on dark back ground), then spray by Ehrlich Reagent (blue to purple color).
GLC: with derivatization by N,O-bis-trimethylsilylacetamide
Column: DB-1 fused silica capillary column
Carrier gas: N2
Detector: FID
Quantitation by peak area and internal standard method
HPLC: lysergide can be efficiently analyzed by isocratic technique, on both normal and reversed phase columns• Normal phase silica gel:Column: silicagelDetector: UV at 313 nm or fluorescence which provide better selectivity and sensitivity than UV detection although for most forensic work UV detection is satisfactory.Quantitation: by peak areas and external standard method.•Reversed phase:Column: Rp-18(octadecyl-silica)Mobile phase: MeOH: Na2HPO4 in H2O (65:35) at pH≈8.0 adjusted by 10% orthophosphoric acid.Detection: as above
