Lysergide (LSD) is a semi-synthetic hallucinogen, and is one of the most potent drugs known. Recreational use became popular between the 1960s to 1980s, but is now less common. It is generally believed that most LSD is produced outside Europe, but secondary preparation of dosage units by dipping or spotting paper squares is more widespread. These dosage units usually bear coloured designs featuring cartoon characters, geometric and abstract motifs. LSD is related to other substituted tryptamines, and is under international control.
The International Non-proprietary Name (INN) is (+)- lysergide. The abbreviation LSD is derived from its German name LysergSäureDiethylamid (Lysergic acid diethylamide) (CAS-50-37-3). Lysergide belongs to a family of indole alkylamines that includes numerous substituted tryptamines such as psilocin (found in ‘magic’ mushrooms) and N,N-dimethyltryptamine (DMT). The IUPAC name for LSD is 9,10-didehydro-N,N-diethyl-6-methylergoline-8β-carboxamide. The (R) stereoisomer is more potent than the (S) form.
Molecular formula: C20H25N3O
Molecular weight: 323.4
LSD is normally produced as tartrate salt, which is colourless, odourless and water soluble. The common street dose forms are ‘blotters’ or ‘paper squares’ — sheets of absorbent paper printed with distinctive designs and perforated so they may be torn into single small (typically 7 mm) squares each containing a single dose. Each sheet typically contains 100 or more doses. LSD is less commonly seen as small tablets (‘microdots’) that are 2–3 mm in diameter, as thin gelatine squares (‘window panes’) or in capsules. Solutions of LSD in water or alcohol are occasionally encountered. LSD is light sensitive in solution, but more stable in dosage units.
LSD was first synthesised by Albert Hoffman while working for Sandoz Laboratories in Basel in 1938. Some years later, during a re-evaluation of the compound, he accidentally ingested a small amount and described the first ‘trip’. During the 1950s and 1960s, Sandoz evaluated the drug for therapeutic purposes and marketed it under the name Delysid®. It was used for research into the chemical origins of mental illness. Recreational use started in the 1960s and is associated with the ‘psychedelic period’.
Physical effects (e.g. dilated pupils, mild hypertension and occasionally raised body temperature) appear first. Sensory-perceptual changes are the outstanding features of LSD. Visual disturbances are perceived with eyes closed or open and may consist of geometric shapes or figures in patterns. Flashes of intense colour are seen and stable objects may appear to move and dissolve. Cross-sensory perception (synaesthesia) such as ‘coloured hearing’ can occur where sounds such as voices or music evoke perception of particular colours or shapes. The perception of time may appear to slow down.
The mode of action of LSD is not well understood. It is thought to interact with the serotonin system by binding to and activating 5–hydroxytryptamine subtype 2 receptor (5-HT2), which interferes with inhibitory systems resulting in perceptual disturbances. It is amongst the most potent drugs known, being active at doses from about 20 micrograms. Typical doses are now about 20 to 80 micrograms although in the past, doses as high as 300 micrograms were common. Like other hallucinogens, dependence does not occur.
When taken orally, the effects become apparent within about 30 minutes and may continue for 8 to 12 hours or more. The duration and intensity of effects are dose-dependant. The plasma half-life is about two-and-a-half hours. Following a dose of 160 micrograms to 13 subjects, plasma concentrations varied considerably up to 9 micrograms/L. In humans, LSD is extensively transformed in the liver by hydroxylation and glucuronide conjugation to inactive metabolites. Only about 1 % is excreted unchanged in the urine in 24 hours. A major metabolite found in urine is 2-oxylysergide.
Panic reactions (‘bad trips’) may be sufficiently severe to require medical support. Patients usually recover within a few hours but occasionally hallucinations last up to 48 hours and psychotic states for 3–4 days. The effects are greatly affected by the set (an individual’s mental state) and the setting (surroundings) in which the drug is taken. Sensory disturbances known as ‘flashbacks’ sometimes occur. Serious side effects often attributed to LSD such as irrational acts leading to suicide or accidental deaths, are extremely rare. Deaths attributed to LSD overdose are virtually unknown.
Methods for producing LSD are complex and require an experienced chemist. Several methods are known, but the majority use lysergic acid as the precursor. Lysergic acid itself is also often produced in clandestine laboratories using ergometrine or ergotamine tartrate as the starting material. Ergotamine occurs naturally in the ergot fungus (Claviceps purpurea), a common parasite on rye. Depending on the method used, other essential reagents include N,N-carbonyldi-imidazole, diethylamine or hydrazine. Absorbent paper doses (blotters) are prepared by dipping the paper in an aqueous alcoholic solution of the tartrate salt, or by dropping the solution onto individual squares.
Ergometrine (also known as ergonovine), ergotamine and lysergic acid are listed in Table I in the Annex to the United Nations 1988 Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. The corresponding EU legislation is set out in Council Regulation (EEC) No 3677/90 and its amendments, which governs trade between the EU and third countries.
LSD is taken orally. Paper doses are placed on the tongue, where the drug is rapidly absorbed. Tablets or capsules are swallowed. LSD is not absorbed through dry skin.
Synonyms include N,N-diethyl-lysergamide, lysergic acid diethylamide, LSD, and LSD-25. There are many street names including acid, blotter, dots, tabs, tickets, trips and many others related to the particular designs on the paper dosage forms.
LSD may be detected in paper doses after extracting the drug into methanol. The extract is spotted onto filter paper, dried and examined under ultraviolet light (360 nm); LSD gives a strong blue fluorescence. Ehrlich’s reagent (p-dimethyl-aminobenzaldehyde) gives a blue/purple colour and may be applied after thin layer chromatography. HPLC with fluorescence detection or gas chromatography/mass spectrometry are used for confirmation or quantification. The major ions in the mass spectrum are m/z = 323, 221, 181, 222, 207, 72, 223 and 324. Commercial immunoassays are available for the detection of LSD in urine at concentrations at or above 0.5 micrograms/L.
Many ergot alkaloids can interfere with LSD analysis, e.g. ergometrine, methylergometrine, dihydroergotamine, ergocornine, ergocristine, methysergide, and ergotamine. LSD degrades readily, particularly in biological specimens, unless protected from light and elevated temperatures; it may also bind to glass containers in acidic solutions. The only analogue of LSD to have received widespread interest is the N-methylpropylamide of lysergic acid (LAMPA), and any analytical technique should be capable of separating LAMPA from LSD.
Because LSD is so potent, there is no need for it to be adulterated. Laboratories rarely encounter the drug as a powder so rarely measure purity. As mentioned earlier, the drug decomposes in light and at high temperatures.
LSD is listed in Schedule I of the United Nations 1971 Convention on Psychotropic Substances.
Overall consumption levels of LSD in Europe have been low and somewhat stable for a considerable time.
Lifetime prevalence of LSD among adults in Europe ranged from 0 % (Romania, 2007) to 5.3 % (UK (England and Wales) 2009/10) with 14 of 19 countries reporting, having rates between 0.3 % and 2 % (Table GPS-1 part (ii)).
Among young adults (15–34 years), lifetime prevalence of LSD use ranged from 0 % (Romania, 2007) to 5.5 % (UK (England and Wales) 2009/10), and among the 15–24 age group, it varied from 0 % (Romania, 2007) to 2.7 % (Hungary) (Table GPS-1 parts (iii) and (iv)).
Last year use of this drug was very low. In the 15–24 age group, last year use of LSD exceeded 1 % in only one country (Estonia) (Table GPS-2 part (iii)).
In 2009, the average (mean) cost to users of a unit of LSD ranged from EUR 4 (Netherlands) to EUR 28 (Italy) (Table PPP-4 part (i)). The mean price of LSD, corrected for inflation, slightly decreased at European level 2004–09 (Figure PPP-4).
Although once used in psychotherapy, LSD has no current medical use.
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