Chemist Albert Hofmann, working at the Sandoz Corporation pharmaceutical laboratory in Switzerland, first synthesized LSD in 1938. He was conducting research on possible medical applications of various lysergic acid compounds derived from ergot, a fungus that develops on rye grass. Searching for compounds with therapeutic value, Hofmann created more than two dozen ergot-derived synthetic molecules. The 25th was called, in German, Lyserg-Säure-Diäthylamid 25, or LSD-25. Five years after he first created the drug, Hofmann accidentally ingested a small amount and experienced a series of frightening sensory effects: "My surroundings . . . transformed themselves in more terrifying ways. Everything in the room spun around, and the familiar objects and pieces of furniture assumed grotesque, threatening forms. They were in continuous motion, animated, as if driven by an inner restlessness . . . . Even worse than these demonic transformations of the outer world were the alterations that I perceived in myself, in my inner being. Every exertion of my will, every attempt to put an end to the disintegration of the outer world and the dissolution of my ego, seemed to be wasted effort. A demon had invaded me, had taken possession of my body, mind, and soul."

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.

Physical characteristics of LSD

LSD is a clear or white, odorless, water-soluble material synthesized from lysergic acid, a compound derived from a rye fungus. LSD is the most potent mood- and perception-altering drug known: oral doses as small as 30 micrograms can produce effects that last 6 to 12 hours.

LSD is initially produced in crystalline form. The pure crystal can be crushed to powder and mixed with binding agents to produce tablets known as "microdots" or thin squares of gelatin called "window panes"; more commonly, it is dissolved, diluted, and applied to paper or other materials. The most common form of LSD is called "blotter acid" - sheets of paper soaked in LSD and perforated into 1/4-inch square, individual dosage units. Variations in manufacturing and the presence of contaminants can produce LSD in colors ranging from clear or white, in its purest form, to tan or even black. Even uncontaminated LSD begins to degrade and discolor soon after it is manufactured, and drug distributors often apply LSD to colored paper, making it difficult for a buyer to determine the drug's purity or age.

LSD's effects

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.

LSD's effects typically begin within 30 to 90 minutes of ingestion and may last as long as 12 hours. Users refer to LSD and other hallucinogenic experiences as "trips" and to the acute adverse experiences as "bad trips." Although most LSD trips include both pleasant and unpleasant aspects, the drug's effects are unpredictable and may vary with the amount ingested and the user's personality, mood, expectations, and surroundings.

Users of LSD may experience some physiological effects, such as increased blood pressure and heart rate, dizziness, loss of appetite, dry mouth, sweating, nausea, numbness, and tremors; but the drug's major effects are emotional and sensory. The user's emotions may shift rapidly through a range from fear to euphoria, with transitions so rapid that the user may seem to experience several emotions simultaneously.

LSD also has dramatic effects on the senses. Colors, smells, sounds, and other sensations seem highly intensified. In some cases, sensory perceptions may blend in a phenomenon known as synesthesia, in which a person seems to hear or feel colors and see sounds.

Hallucinations distort or transform shapes and movements, and they may give rise to a perception that time is moving very slowly or that the user's body is changing shape. On some trips, users experience sensations that are enjoyable and mentally stimulating and that produce a sense of heightened understanding. Bad trips, however, include terrifying thoughts and nightmarish feelings of anxiety and despair that include fears of insanity, death, or losing control.

LSD users quickly develop a high degree of tolerance for the drug's effects: After repeated use, they need increasingly larger doses to produce similar effects. LSD use also produces tolerance for other hallucinogenic drugs such as psilocybin and mescaline, but not to drugs such as marijuana, amphetamines, and PCP, which do not act directly on the serotonin receptors affected by LSD. Tolerance for LSD is short-lived it is lost if the user stops taking the drug for several days. There is no evidence that LSD produces physical withdrawal symptoms when chronic use is stopped.

Two long-term effects persistent psychosis and hallucinogen persisting perception disorder (HPPD), more commonly referred to as "flashbacks"-have been associated with use of LSD. The causes of these effects, which in some users occur after a single experience with the drug, are not known.

Psychosis. The effects of LSD can be described as drug-induced psychosis-distortion or disorganization of a person's capacity to recognize reality, think rationally, or communicate with others. Some LSD users experience devastating psychological effects that persist after the trip has ended, producing a long-lasting psychotic-like state. LSD-induced persistent psychosis may include dramatic mood swings from mania to profound depression, vivid visual disturbances, and hallucinations. These effects may last for years and can affect people who have no history or other symptoms of psychological disorder.

Hallucinogen Persisting Perception Disorder. Some former LSD users report experiences known colloquially as "flashbacks" and called "HPPD" by physicians. These episodes are spontaneous, repeated, sometimes continuous recurrences of some of the sensory distortions originally produced by LSD. The experience may include hallucinations, but it most commonly consists of visual disturbances such as seeing false motion on the edges of the field of vision, bright or colored flashes, and halos or trails attached to moving objects. This condition is typically persistent and in some cases remains unchanged for years after individuals have stopped using the drug.

Because HPPD symptoms may be mistaken for those of other neurological disorders such as stroke or brain tumors, sufferers may consult a variety of clinicians before the disorder is accurately diagnosed. There is no established treatment for HPPD, although some antidepressant drugs may reduce the symptoms. Psychotherapy may help patients adjust to the confusion associated with visual distraction and to minimize the fear, expressed by some, that they are suffering brain damage or psychiatric disorder.