LSD is a chiral molecule with two stereocenters at carbon atoms C-5 and C-8, allowing for the existence of four distinct optical isomers of LSD. LSD, also known as (+)-D-LSD, has the absolute configuration (5R,8R). The C-5 isomers of lysergamides do not exist in nature and cannot be synthesised from d-lysergic acid. The C-5 stereocenter might be analysed retrosynthetically as having the same configuration as the alpha carbon of the naturally occurring amino acid L-tryptophan, which is the precursor of all biosynthetic ergoline molecules.
However, because the alpha proton is acidic and may be deprotonated and reprotonated, LSD and iso-LSD, the two C-8 isomers, readily interconvert in the presence of bases. The non-psychoactive iso-LSD generated during the synthesis can be isolated via chromatography and isomerized to LSD.
When pure LSD salts are shaken in the dark, they create brief flashes of white light. LSD paper is highly fluorescent and will glow bluish-white when exposed to UV light.
LSD from synthesis is an ergoline derivative. It is frequently produced by combining diethylamine and an activated form of lysergic acid. Phosphoryl chloride and peptide coupling reagents are examples of activating reagents. Lysergic acid is produced through the alkaline hydrolysis of lysergamides such as ergotamine, which is often derived from the ergot fungus on an agar plate; or, theoretically conceivable but impractical and seldom, from ergine (lysergic acid amide, LSA) isolated from morning glory seeds. Lysergic acid can also be synthesised, albeit due to low yields and great complexity, these procedures are not used in clandestine production.
Dosage
White on White (WoW) blotters for sublingual administration
A single dose of LSD could range between 40 and 500 micrograms—roughly one-tenth the mass of a grain of sand. With as low as 25 micrograms of LSD, threshold effects can be felt. Microdosing is the process of administering sub-threshold doses. LSD dosage is measured in micrograms (g), or millionths of a gramme. Most drugs, both recreational and therapeutic, have dosages measured in milligrammes (mg), or thousandths of a gramme. An active dose of mescaline, for example, of 0.2 to 0.5 g, provides effects comparable to 100 g (0.0001 g) or less of LSD.
The most important black market LSD manufacturer (Owsley Stanley) delivered LSD at a standard concentration of 270 g in the mid-1960s, whereas street samples from the 1970s comprised 30 to 300 g. By the 1980s, the amount had dropped to between 100 and 125 g, then further in the 1990s to 20-80 g, and even further in the 2000s.
Degradation and reactivity
“LSD is an extraordinarily fragile molecule,” writes chemist Alexander Shulgin. “As a salt, in water, cold, and away from air and light exposure, it remains stable indefinitely.”
LSD contains two labile protons in the tertiary stereogenic C5 and C8 locations, which makes these centres susceptible to epimerisation. The electron-withdrawing carboxamide attachment makes the C8 proton more labile, but the inductively withdrawing nitrogen and pi electron delocalisation with the indole ring help remove the chiral proton at the C5 location (which was originally an alpha proton of the parent molecule tryptophan).
Because of the electron-donating actions of the indole ring, LSD also has enamine-type reactivity. As a result, chlorine kills LSD molecules on contact; even if chlorinated tap water includes only a trace of chlorine, the small amount of chemical typical of an LSD solution will most likely be removed when dissolved in tap water. Because it is conjugated with the indole ring, the double bond between the 8-position and the aromatic ring is vulnerable to nucleophilic assaults by water or alcohol, especially in the presence of UV or other types of light. LSD frequently transforms to “lumi-LSD,” which is inactive in humans.
To test the stability of LSD in pooled urine samples, a controlled investigation was conducted. LSD concentrations in urine samples were tracked over time at various temperatures, storage containers, exposure to different wavelengths of light, and pH values. These tests found no substantial reduction of LSD concentration at 25 °C after four weeks. After four weeks of incubation, there was a 30% drop in LSD concentration at 37 °C and up to a 40% loss at 45 °C. Under whatever light condition, urine fortified with LSD and held in amber glass or nontransparent polyethylene containers exhibited no change in concentration. The stability of LSD in transparent containers under light was affected by the distance between the light source and the samples, light wavelength, exposure time, and light intensity. 10 to 15% of the parent LSD epimerized to iso-LSD after extended heat exposure in alkaline pH settings. Less than 5% of the LSD was converted to iso-LSD in acidic conditions. It was also shown that tiny levels of metal ions in buffer or urine can catalyse the degradation of LSD, and that this process can be avoided by adding EDTA.
Detection
LSD can be measured in urine as part of a drug misuse testing programme, plasma or serum to confirm a poisoning diagnosis in hospitalised patients, or whole blood to aid in a forensic investigation of a traffic or other criminal infraction or a case of sudden death. Because both the parent drug and its primary metabolite are unstable in biofluids when exposed to light, heat, or alkaline conditions, specimens are protected from light, stored at the lowest feasible temperature, and examined as soon as possible to minimise losses.
With a plasma half-life of 2.6 hours, maximum plasma concentrations were determined to be 1.4 and 1.5 hours after oral administration of 100g and 200g, respectively (ranging from 2.2–3.4 hours among 40 human test subjects).
LSD can be identified with Ehrlich’s and Hofmann’s reagents.
