DOSAGE : 60 to 200 micrograms, orally
DURATION : 8 - 12 hrs
QUALITATIVE COMMENTS : In the case of LSD, it seems presumptuous to attempt to select typical comments for quotation. Literally thousands of reports are in the literature, from early exploratory research, to clinical applications for treatment of autism, of alcoholism, or mental illness, to assisting in psychotherapy and in the dying process, to the adventures of the military in both intelligence and chemical warfare, to innumerable anecdotal tales of pleasure and pain. Dozens of books have been devoted to these topics.
EXTENSIONS AND COMMENTARY : LSD is an unusually fragile molecule and some comments are in order as to its stability and storage. As a salt, in water, cold, and free from air and light exposure, it is stable indefinitely. There are two sensitive aspects of its structure. The position of the carboxamide attachment, the 8-position, is affected by basic, or high pH, conditions. Through a process called epimerization, this position can scramble, producing isolysergic acid diethylamide, or iso-LSD. This product is biologically inactive, and represents a loss of a proportionate amount of active product. A second and separate point of instability is the double bond that lies between this 8-position and the aromatic ring. Water or alcohol can add to this site, especially in the presence of light (sunlight with its ultraviolet energy is notoriously bad) to form a product that has been called lumi-LSD, which is totally inactive in man. Oh yes, and often overlooked, there may be only an infinitesimal amount of chlorine in treated tap water, but then there is only an infinitesimal amount of LSD in a typical LSD solution. And since chlorine will destroy LSD on contact, the dissolving of LSD in tap water is not appropriate.
There are many synthetic methods developed and reported for the preparation of LSD. All of them start with lysergic acid, and for that reason it has been listed as a Schedule III controlled drug, as a depressant, under Federal law. The amide lysergamide, a component of several varieties of morning glory seed, is also a controlled drug and, by law, a depressant. The earliest syntheses of LSD involved the used of an azide intermediate (the original Hofmann process, 1955), mixed anhydrides with trifluoroacetic anhydride (1956) or sulfuric anhydride (SO3-DMF on the lithium salt, 1959), with the peptide condensation agent N,N'-carbonyldiimidazole (1960), or with the acid chloride as the active intermediate with POCl3, PCl5 or thionyl chloride (1963) or just phosphorus oxychloride (1973). Most methods are faulted due to excessive moisture sensitivity, generation of side-products, or epimerization or inversion at the 8-position carbon to form d-iso-LSD. The POCl3 procedure is clean and fast, and is the preferred process today for the synthesis of a wide variety of substituted lysergamides.
The term LSD comes from the initials of the German for lysergic acid diethylamide, or Lysersäure Diethylamid. The number "25" following it has many myths attached to it, such as it was the 25th form of LSD that Hofmann tried, or it was his 25th attempt to make LSD. From my own experience with chemical companies that are allied with pharmaceutical houses, I had assumed that the chemical name (which might be a mouthful for the pharmacologist) was simply replaced with a pronounceable code number equivalent. But the answer here is yet simpler. Hofmann, in his LSD, My Problem Child wrote: "In 1938, I produced the twenty fifth substance in a series of lysergic acid derivatives: lysergic acid diethylamide, abbreviated LSD-25 ... for laboratory usage."
Within a few years of the discovery of the extraordinary potency of LSD, a large number of close analogues were synthesized by Hofmann and his allies at Sandoz. Over the following decade many were tested in humans, both in patients and healthy subjects, with the qualitative descriptions and dosages published in the medical literature.
