Chapter 1
LSD's Origins

LSD is the most potent hallucinogen known to science. Consuming an amount in weight equal to a few grains of salt can produce wide-ranging effects, including rich and vivid hallucinations and visions. The effects of LSD often vary from person to person, and the intensity of the effects depends on how much of the drug is taken.

What Is LSD?

LSD is often classified as a synthetic drug because it is produced only in a laboratory. Although most hallucinogenic drugs, such as marijuana and peyote, come from plants, LSD is not derived completely from a natural biological source, that is, a plant or an animal. LSD is more accurately called a semisynthetic hallucinogen because it has both natural and synthetic components.

Diethylamide is LSD's synthetic ingredient. It is part of a group of chemical compounds called amides. Diethylamide and other amides are used in drugs because of their ability to bond with molecules in the body, primarily proteins. In the case of LSD, diethylamide allows LSD to bond with certain molecules in the brain, helping the body to process the drug. LSD's hallucinogenic effects, however, come from lysergic acid, which is found in morning glory seeds and more commonly in an ergot fungus called Clavica pupurea that grows on rye and certain other grains. The lysergic acid is derived from a substance in the fungus that is used to make many drugs, including effective medicines for treating migraine headaches.

How Was LSD Discovered?

LSD was discovered in the 1930s as a result of research at Sandoz Pharmaceuticals in Switzerland into possible medical uses for the ergot fungus. Scientists at the Rockefeller Institute in New York had isolated a chemical compound found in the ergot fungus and named it lysergic acid. A young chemist at Sandoz named Albert Hofmann began working with lysergic acid derivatives. He was trying to develop a strong stimulant that would act on the human respiratory and circulatory systems and help breathing for people who had respiratory diseases or suffered from respiratory failure. In 1938 Hofmann synthesized lysergic acid diethylamide and gave it the lab name LSD-25 because it was the twenty-fifth compound he synthesized in his series of experiments. (The abbreviation LSD comes from the drug's German name, lyserg saeure diathylamid.)

Sandoz researchers tested LSD-25 in animals and concluded that the drug held little promise for medical use. Hofmann halted his research but returned to studying LSD five years later, in 1943. After resuming his investigations, Hofmann accidentally contaminated himself with the drug. Although he was not sure exactly how the contamination occurred, Hofmann believed he had absorbed it through the skin of his fingertips during the laboratory process of producing a crystallized form of LSD. Before long Hofmann began to feel a strange sense of restlessness and dizziness, and he decided to go home to rest. In his 1980 book LSD: My Problem Child, Hofmann described his experience this way:

At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away.⁵

Hofmann believed the experience was related to his experiments. Intrigued, he intentionally took LSD-25 three days later. Hofmann took only 0.25 milligrams of the substance, which is a very small dose compared to the dosages required for most drugs to have an effect. He again experienced a variety of unusual sensory experiences, some horrifying and others pleasant. The experience confirmed that LSD-25 had a powerful effect on humans.

LSD's Potency

LSD is extremely potent. The amount needed to produce an effect is measured in mere micrograms. A microgram is equal to about one-millionth (1/1,000,000) of a gram. In comparison, dosages of most drugs are measured in milligrams, with one milligram equaling about one-thousandth (1/1,000) of a gram. According to the DEA, LSD is so potent that one gram of the powder form of LSD could be sold as twenty thousand individual units.

The dosage of LSD needed to produce a hallucinogenic effect depends, in part, on a person's body weight. For example, a dosage of only 17.5 micrograms can produce mild effects in a person who weighs approximately 155 pounds but can cause more noticeable effects in someone who weighs less. In general, LSD dosages begin at 25 micrograms, and the average oral dose of LSD is 50 to 100 micrograms.

Scientific Names for LSD and Hallucinogens

The original term for the class of drugs now called hallucinogens was phantastica. This scientific term was created by a renowned pharmacologist and toxicologist named Louis Lewin in his 1924 book Phantastica. The book is considered a classic study on the use of drugs that affect the mind, mood, or other mental processes. Based largely on research with LSD, the psychiatric community later named hallucinogens psychotomimetics or psychosomimetics, meaning that people taking them sometimes act as though they have a true psychosis, such as paranoia and schizophrenia.

In the 1960s Humphrey Osmond, a British psychiatrist who worked with LSD as a therapy for alcoholics and schizophrenics, came up with the term that would apply to LSD and all other hallucinogens. Convinced that mimicking mental illness was not the main characteristic of LSD, Osmond suggested that the group of drugs be called psychedelic, which means "mind-manifesting." Following this line of thought, scholars created the name entheogen in 1979. The word entheogen comes from the Greek word entheos, meaning "god within" and the Greek root gen, which denotes the act of becoming. Thus, entheogen can be translated as "producing the divine within." This name reflects the spiritual and mystical experiences many people have claimed to experience while taking LSD and other hallucinogens.

The strength of LSD dosages varies widely, however, and cannot be guaranteed. The Food and Drug Administration (FDA) regulates legal drugs. In addition to conducting a thorough review and approval process to determine a drug's safety, the FDA monitors and approves a legal drug's contents and establishes manufacturing standards for making the drug. Because manufacturing LSD is illegal and unregulated, its users have no practical way of determining exactly how much LSD they are taking.

Another problem associated with LSD is its unknown purity. Laboratory tests have revealed some LSD to be mixed with other drugs or substances, including phencyclidine (PCP) and amphetamines. These drugs can have serious side effects. For example, high dosages of PCP can cause seizures, respiratory failure, stroke, and heart problems. Amphetamines can also cause heart problems and even lead to heart attacks. At one time, many believed that strychnine, which is a rat poison, was used to manufacture LSD. Although strychnine was once found in a batch of LSD when it began to be illegally manufactured more than three decades ago, large-scale lab analyses of street samples have failed to find strychnine in LSD. Nevertheless, the bottom line is that any unregulated drug, such as LSD, may include other potentially harmful drugs.

LSD Comes in Various Forms

Making LSD is a complex chemical process that requires sophisticated lab equipment and an experienced organic chemist. Although the resulting synthesized product is a crystallized white, odorless powder, LSD is seldom seen in the crystal form. Rather, the powder, which is water soluble, is diluted and distributed in other forms.

As a liquid, LSD may be dropped directly in the mouth. It can also be ingested orally by either sucking on sugar cubes containing LSD or swallowing extremely small tablets of LSD called "microdots." One of the most popular forms of illegal LSD is "blotter," that is, small squares of paper that have been soaked in liquid LSD. Another form of LSD is small, clear gelatin squares, which are known as "windowpanes" or "gel tabs."

LSD is most often taken orally. However, it can be inhaled through the nose in powder form and injected intravenously via a needle. Because the drug is so powerful, few people take LSD in these ways.

Blotter Acid

Although LSD comes in several forms, the paper form, called blotter acid, is the most common way LSD is sold on the streets. Blotter is made when an absorbent paper is soaked and diluted in LSD. The amount of acid diluted into the paper can vary greatly, depending on the batch. This means it is difficult for someone taking the illegal drug to know the strength of the dose or the powerful effects that will be experienced. The paper sheets are also perforated so that individual "tabs" can be sold or taken. These tabs are extremely small because it takes only a small dose of LSD to produce its effects. Blotter LSD is also often imprinted with some type of art, such as cartoon characters like Bart Simpson and Daffy Duck, or other designs, such as flowers or rainbows.

How Does LSD Work?

After taking LSD, a person experiences its effects within thirty to ninety minutes. Several factors can influence how quickly the drug is absorbed. For example, it takes longer to affect someone who has eaten a big meal as opposed to someone who ingests LSD on an empty stomach. The effects continue for six to twelve hours.

Once LSD is ingested, it is absorbed rapidly from the stomach and intestines into the bloodstream, where it is distributed throughout the body's many tissues. Although LSD's exact mechanism of action is unknown, scientists believe that it stimulates certain brain cells to produce its effects.

LSD and Serotonin

In the brain, nerve cells called neurons use a variety of chemical molecules called neurotransmitters to send signals to each other. Between each neuron is a small gap called the synapse. Neurotransmitters are released from one neuron and then cross the synapse, where they may be accepted by the next neuron at a special site called a receptor. The neurotransmitter carries nerve impulses across the synapse, helping to relay various messages to different parts of the brain. There are many different types of neurotransmitters in the brain. Some play a large role in many of our sensory and emotional responses, including hunger, thirst, pleasure, and pain.

In the case of LSD, scientists believe that the drug interferes with a neurotransmitter called serotonin. This interference occurs because the molecular structures of LSD and serotonin are very similar. As a result, LSD is believed to interfere with serotonin's normal action at the receptor sites of some neurons.

Serotonin helps regulate behavior and normal body functions. For example, changes in serotonin production in the brain can affect mood, sleep, and appetite. Scientists also know that lowered levels of serotonin in the brain play a key role in causing depression in some people. Because LSD affects serotonin in the brain, someone under the influence of LSD may experience various changes in their moods and emotions, such as depression or euphoria.

Due to LSD's interference with serotonin, LSD may work as a pain reliever, or analgesic. Scientists believe this effect occurs because most serotonin neurons are located in the middle of the brain stem, which is involved in the regulation of pain. As a result, LSD may somehow interfere with the transfer of pain messages across neurons.

What Are LSD's Effects?

Clearly, LSD affects the brain in many ways. The most important aspects of LSD are its psychological and sensory effects. For example, scientists know that LSD primarily affects neurons that play a large role in people's perceptions and various other mental processes, including awareness and judgment.

Someone taking LSD often experiences an intensified perception of colors, smells, sounds, and other sensations. Sometimes the sensations become mixed, which is a phenomenon called synesthesia. As a result, a person may believe he or she can hear or feel colors and taste sounds. Many scientists believe that this phenomenon is due to LSD's effects on a part of the brain called the locus coeruleus, which helps to interpret sound, touch, smell, and taste. Because sensory perceptions are greatly altered, the LSD user often experiences time as slowing down.

LSD also affects areas of the brain dealing with vision. As well as causing the physical dilation of pupils, LSD distorts electrical messages sent to and from various parts of the brain that regulate and interpret visual information. As a result, a common effect of LSD are visual illusions that distort or transform shapes and movements. Visual illusions may include intensified color, flashing lights, and brightly colored geometric designs.

In addition to causing visual and perceptual distortions, LSD has other temporary physiological effects. It can increase a person's blood pressure and heart rate and cause nausea, increased salivation, tremors, and muscle weakness. Dry mouth, sweating, and loss of appetite can also occur, as can tingling and numbness of the skin.

Tolerance

Although the effects produced by LSD can be extreme and unpleasant, some people continue to use the drug. When a drug or substance is used over and over again, a condition known as tolerance can occur.

Tolerance is a state in which a person's body adjusts to repeatedly taking a drug. As a result, the person becomes less responsive to the drug's physical or mental effects. The more tolerant someone becomes to a drug, the weaker the effect of a single dose on that person. As a result, the person may take more of the drug to obtain the desired effect, whether it is to eliminate pain or to produce intoxication, the feeling of being "high."

LSD users develop a rapid tolerance to the drug's effects. As a result, users must take larger quantities of the drug in order to experience its effects. However, the drug cannot be abused for more than a few consecutive days. After that, it will not produce hallucinogenic effects, no matter how much is taken. In most cases, if someone stops taking LSD for several days to a week, the tolerance wears off rapidly.

Is LSD Addictive?

Repeatedly taking any drug, whether legal or illegal, often leads to addiction, a condition in which a user experiences abnormally strong physical or psychological cravings for the drug. A physical addiction occurs when the body adapts and becomes used to the presence of the drug. The physical addiction can be so strong that eventually the body cannot function normally without the drug. For example, a person addicted to drugs like alcohol or heroin may experience shaking, nausea, insomnia, diarrhea, and vomiting when they go without taking the drug. These conditions are commonly referred to as withdrawal symptoms and often occur when the drug use is reduced or stopped abruptly.

Both scientists and law enforcement officials agree that LSD is not a physically addictive drug. It does not result in the user having an uncontrollable need to seek out the drug, which often occurs with the use of other drugs. Even with chronic use over a long period of time, LSD produces no physical withdrawal symptoms.

Does LSD Cause Psychological Dependency?

LSD use can lead to a psychological dependency or addiction in some people. Users may not experience physical withdrawal but may feel they must take the drug to escape from reality, forget about their problems, or relieve feelings of loneliness and anxiety. People who believe that they need the drug to improve their mood can become dependent on the euphoric feelings that the drug gives them.

The consensus, though, is that LSD does not have a high potential for psychological dependency. Regarding the recreational use of LSD, a DEA report noted, "Several factors provide LSD with a virtually inherent governor to its regular use, meaning that the drug will never become as frequently abused as other drugs, most notably, crack cocaine." According to the DEA report, the long duration of the drug's effects means that most people will not purchase or take the drug on a rapidly recurring basis. The DEA also noted that the drug's uncertain effects lead most people to discontinue its use. The report concluded, "Finally, the extremely powerful and intense hallucinations often prompt users to abstain from LSD ingestion as they require periods of reorientation."⁶

LSD and Overdosing

People who take drugs run the risk of overdose. Taking an excessive amount of a drug often has toxic or lethal effects. According to the DEA, it is virtually impossible to die from an overdose of LSD. Whereas a lethal dose of LSD is considered to be 12,000 micrograms, based on tests in which this dosage killed 50 percent of the animals tested, humans generally take 100 micrograms. Only two human deaths from the physiological effects of LSD have been reported in medical literature. In both cases, doctors found that the individuals had a large amount of LSD in the liver and no other drug. One of the deaths occurred in a hospital and was due to a malfunction in the respiratory system that made the person quit breathing.

Rare instances of fatal overdose highlight the fact that all drugs have the potential to be fatal. Even if it does not cause death, LSD taken in large amounts can physically harm people. In a case reported in Clinical Toxicology in 1975, eight people at a party mistook crystal LSD for cocaine and inhaled a large quantity of the drug. As a result, the individuals experienced vomiting and collapsed. They were rushed to the hospital, where doctors found that they were suffering from symptoms of hyperthermia (high fever) and respiratory problems. Such cases are rare in that few users have access to large quantities of LSD, but they demonstrate the drug's dangers, nonetheless.

Can LSD Harm the Brain?

The long-term use of most drugs can have a profound impact on a person's body and overall health. Heavy alcohol use, for instance, can damage and ultimately destroy a person's liver. It has been well documented that many prescription drugs have harmful and even fatal side effects. On the other hand, the damage LSD causes to the body is highly debated.

The Fires of Saint Anthony

In his book The Day of St. Anthony's Fire, author John G. Fuller tells the true and tragic story of the people in a small French village, Pont-Saint-Esprit, who appeared to go insane. In mid-August 1951, some villagers began running through the streets, screaming that wild animals and bandits were chasing them. Others did not sleep for days and walked around having pleasant and sometimes spiritual visions or delusions. A few citizens thought they could fly and jumped from their second-story windows into the Rhone River.

Scientific investigations eventually uncovered the culprit. The villagers had been poisoned by the wheat and rye flour fungus called ergot. LSD is synthetically developed from this fungus. A local baker had used the contaminated flour to bake bread. Overall some 230 villagers, all customers of the baker, suffered from ergot poisoning, which is now known as ergotism. In medieval times, ergot poisoning was called St. Anthony's fire after the medieval patron saint and the Order of St. Anthony members who provided care for those stricken with the mysterious disease.

Scientists have not been able to prove, for example, whether LSD permanently damages brain tissues and functioning. Some researchers have reported that LSD users experience permanent cerebral deficits, that is, problems within the brain that affect how it functions. Electroencephalograms (EEGs) are recordings of electrical activity within the brain. Abnormal brain wave patterns have been detected in the EEGs of some people who have taken LSD over a period of time. However, the results are inconclusive and lack statistical data.

Although no concrete evidence is available, scientists and physicians remain concerned that LSD may cause irreversible changes in the brain. What they know for certain is that some people who have taken LSD over a period of time show signs of mental or cognitive impairment, such as learning and memory problems, while others appear to function normally. The inconclusive data on the long-term effects of LSD use was described in the American Journal of Psychiatry in 1969 and pertains today: "In one subject who continued to use the drug heavily, there was a deterioration in his performance pattern on the cognitive tests suggestive of organic [physical] damage. On the other hand one of our subjects maintained an A average in junior college while ingesting LSD on most weekends."⁷

Does LSD Cause Chromosome Damage?

One of the earliest reports concerning LSD's potential to cause physical harm focused on chromosome damage in users. A 1967 study by Dr. Marion Cohen of the State University of New York at Buffalo reported that LSD damaged white-blood-cell chromosomes in test tubes. Chromosomes, found in the cell nucleus, contain most of the chemicals, called DNA and RNA, that are responsible for an individual's genetic makeup. Because chromosomes carry the genetic codes for life from generation to generation, chromosome damage can lead to abnormalities in unborn children.

Cohen's report set off a firestorm of controversy. The authors of a Consumer Reports article noted, "Reporters (and physicians as well) speculated in print and on television and radio that LSD might cause a vast epidemic of tragically malformed babies."⁸

When researchers pursued this avenue of investigation, their results were contradictory and inconclusive. Studies focused on animal subjects, and extremely high doses (up to 500,000 milligrams) of LSD were given early in the pregnancy of some animals. In his American Journal of Psychiatry article that reviewed follow-up research into chromosome damage, psychologist B. Kent Houston noted, "Even at this high a dosage, there was no evidence that LSD led to an unusual frequency of mutations."⁹ LSD usage cannot be pinpointed as a cause of chromosomal damage because scientists point out that breakage can occur as a response to a variety of factors, including many pollutants, X rays, fever, and even a viral infection. Evidence has shown that even aspirin and caffeine may cause chromosome damage in some cells.

Does LSD Cause Damage to the Embryo?

Several reports have indicated that women who take LSD just prior to or during pregnancy increase their risk of having a mis-carriage or stillbirth. Once again, the research has been inconclusive, because scientists cannot trace the miscarriages directly to LSD consumption. For example, in almost all the cases studied, the mothers had taken other drugs during pregnancy, a circumstance that makes it difficult to determine whether LSD, another drug, or a combination of drugs and other factors contributed to problems.

In the 2001 book Drugs in Pregnancy and Lactation, Gerald G. Briggs and his coeditors noted that a direct relationship between LSD dosage and miscarriages could not be established. They further concluded that no study had confirmed that LSD causes chromosome damage or an increased rate of miscarriage and that more research is needed.

Because LSD's effects on the embryo and unborn child are undetermined, physicians recommend that women avoid taking the drug during pregnancy, especially since LSD enters into the placenta easily. Health professionals agree that even the remote possibility of chromosome or fetal damage in humans requires that women who are either pregnant or expect to become pregnant in the near future avoid LSD use.

Although controversy continues to surround LSD's potentially harmful effects on the body, scientists have documented its profound long- and short-term psychological impact. As a result, a clearer picture of how LSD affects the mind has emerged.