How LSD Works

In 1938, a Swiss chemist Albert Hofmann first synthesized LSD as part of a project for Sandoz, a pharmaceuticals company. Hofmann was working on a research project involving a parasitic fungus called ergot (known as Claviceps purpurea), which grows on rye.

Ergot, it turns out, has a long history in human culture. In the Middle Ages, ergot often infected rye bread...and then poisoned countless people who consumed the tainted loaves. Midwives sometimes gave ergot to pregnant women to trigger and expedite labor. In the 19th century, most physicians deemed the practice too dangerous because high dosages of ergot may lead to strong contractions and endanger the baby.

Ergot's official medical history began in 1917, when Swiss biochemist Albert Stoll (Hofmann's superior) managed to isolate ergot and developed a drug marketed as Gynergen, which was used to halt post-childbirth bleeding. Then, ergot researched was essentially mothballed until the 1930s, when Hoffman, searching for a new project, delved into ergot at Stoll's urging, hoping to find further medicinal for the substance.

While deriving different compounds from lysergic acid, Hofmann developed several medicines, including drugs that lowered blood pressure and improved brain function in the elderly. In 1938, Hofmann derived the 25th in a series of these derivatives. It was lysergic acid diethylamide, or LSD-25. He thought that LSD-25 might stimulate breathing and circulation, but subsequent tests didn't show anything real potential, and Sandoz abandoned further study.

Five years later, Hofmann's thoughts returned to LSD-25, and so he synthesized another batch for further testing. During the process, however, Hofmann began to feel strange. He stopped his work and went home early, "being affected by a remarkable restlessness, combined with a slight dizziness."

While at home, he was in a "dreamlike state" and "perceived an uninterrupted steam of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors" [At the time, Hofmann decided that he must've gotten some of the experimental solution on his finger. (Later it was determined that he must have touched his finger to his mouth, as LSD can't be absorbed through the skin) [source: Hofmann].

The next day, Hofmann did something extraordinary -- he purposely dosed himself with the solution. He took 250 micrograms, 10 times more than today's typical minimum dose. In short order, he became delirious and could barely speak. Initially he panicked and asked his laboratory assistant to call a doctor. The doctor could find nothing wrong with Hofmann other than the fact that his pupils were dilated, his blood pressure, heart rate, and respiration were all normal. Soon his panic gave way to euphoria, and Hofmann once again perceived beautiful shapes and colors. The next day, he told others at Sandoz about what had happened, and they experimented too, achieving similar results. No other drug had been known to have such strong effects in such small doses.

After trials on animals, Sandoz gave LSD to research institutes and doctors for use in psychiatric experiments on both healthy and mentally ill subjects. The research was compelling enough to convince Sandoz to patent LSD and market it as Delysid in 1947, which was sold in 25-microgram tablets for use in analytical psychotherapy. Sandoz also suggested that psychiatrists take the drug themselves, so that they could better understand their patients.

In the 1950s, the U.S. Central Intelligence harnessed LSD's powers in a now-infamous series of secret experiments called Project MKULTRA, which dosed many (often unwitting) people with the drug to explore its potential for interrogation and torture. Those tests didn't come to light until decades later and led to a public relations nightmare for the C.I.A. [source: C.I.A.].

By 1960, there had been hundreds of papers published in scientific and medical journals on the various uses of LSD -- it was the talk of the psychiatric community. And then, by the late '60s Sandoz stopped making it altogether. But LSD's run was hardly over.

Sandoz held the patent on LSD until 1963 and stopped making it shortly afterward. The company claimed that it was concerned about a lack of regulation and the inaccurate information being perpetuated about the drug. However, this didn't stop anyone from making it themselves, and until 1965, it was entirely legal to do so.

LSD production requires a strong working knowledge of organic chemistry, a complete laboratory setup (including the ability to sterilize equipment as well as access to a darkroom), and several chemicals that are currently either sales restricted or have their sales closely monitored by the Drug Enforcement Agency (DEA). Unlike the chemicals used in the manufacture of methamphetamine, they can't be found in fairly ordinary household items.

There a couple of different ways to make LSD. Some "recipes" may start with lysergic acid. Other online recipes call for morning glory seeds, which can be especially dangerous because they're often sold with a toxic coating to discourage consumption. Morning glory seeds and the seeds of some related plants contain LSA, or lysergic acid amide. The LSA can be extracted from the seeds and produce a mild high on its own. It's considered a precursor to LSD, although the amount of LSA in different seeds varies so much that the quality of the drug made from it would also vary. Here, we'll look at a recipe that starts with ergot, the substance that made Albert Hofmann famous in the first place.

LSD chemists must be extremely careful in working with ergot because of its toxicity. Remember the people poisoned by rye bread in the Middle Ages? Once the chemist obtains the fungus, he has to carefully and precisely culture it to extract the ergot alkaloids (an alkaloid is a compound containing basic nitrogen atoms). The darkroom setup becomes necessary here, because the fungus will decompose under bright lights. In fact, LSD itself may break down quickly when exposed to light.

If working with toxic ergot weren't hazardous enough, the solvents and reagents (compounds used to bring about chemical reactions) are also incredibly dangerous. The solvent anhydrous hydrazine, for example, may explode when heated. It's extremely poisonous and carcinogenic (meaning it can cause cancer). Another chemical often used in the process, chloroform, can also trigger cancer, in addition to damaging the kidneys and liver. Both substances are easily absorbed through the skin or inhaled.

The ergot alkaloid is synthesized into a lysergic acid compound called iso-lysergic acid hydrazide, through the addition of chemicals and heating processes. Then the iso-lysergic acid hydrazide is isomerized, which means that the atoms in its molecules are rearranged through a chemical process. It's cooled, mixed with an acid and a base, and evaporated. What remains is iso-lysergic diethylamide, which is isomerized again to produce active LSD. The LSD is then purified and crystallized.

What next? In the past, LSD was then made into tablets (microdots), simply dissolved in water or other liquids to be dropped or made into gelatin squares (windowpanes). It's rare to see LSD in these forms today, however. Instead, it's usually dissolved in ethanol. Sheets of blotting paper are then dipped into the LSD solution and dried. These sheets of blotter acid are usually printed with cartoon characters or other colorful graphics. The sheets are perforated into small squares, about a quarter of an inch (6.35 millimeters) wide. Each square is one dose, and a sheet can contain 900 doses.

Users chew and then swallow the little bits of blotter paper. You can inject LSD, but it's not really necessary because it's so readily absorbed through oral means. Then, the drug's powerful effects quickly take hold.

It's often stated that LSD causes hallucinations, but that's not quite accurate. When a person has a hallucination, he or she believes that everything that he or she sees and feels is real. LSD changes the way people perceive the world around them, as well as what they think and feel, but people on LSD don't see things that aren't there. They see what's already there in a different way, and (most of the time) they're aware that their altered perceptions are caused by the drug.

After taking LSD, the effects -- known as a "trip" -- usually start within an hour and can last up to 12 hours, with a peak about halfway through the experience. LSD affects everyone a little differently. Some people have dilated pupils, increased blood pressure, and elevated body temperature. Others on LSD may also feel dizzy, sweat, have blurred vision and feel tingling in their hands and feet. They may feel drowsy but not sleepy.

LSD's primary effects are visual. Colors seem stronger and lights seem brighter. Objects that are stable might appear to move or have a halo of light around them. Sometimes objects have trails of light coming from them or appear smaller or larger than they really are. LSD users often see patterns, shapes, colors and textures. Sometimes it seems that time is running backward or moving very quickly or slowly. On very rare occasions (although it's sometimes portrayed as common), tripping can cause synesthesia -- a confusion of sensations between different types of stimuli. Some people have described this as "seeing" colors when exposed to specific sounds.

Feelings of happiness and euphoria are common, and everyday experiences may seem more beautiful, interesting and magical. People on LSD often become very emotional, more prone to tears or laughter. Large doses of may make them feel especially contemplative. They feel that their mind has burst through its normal boundaries, and they often claim to have had experiences that are spiritual or religious, with a new understanding of how their world and surroundings (or, you know, their lava lamps) work.

People tripping on LSD may have very questionable reasoning skills, becoming impulsive or irrational. This why some LSD users trip in groups, especially with others who have experience, and in calm places like home or in a park.

As the drug kicks in, users may spend a lot of time pondering something that appears incredibly unimportant, say, a leaf on the ground or a stain on the sofa. They aren't always easy to understand, but when they do talk, they speak quickly and jump from subject to subject.

If all goes according to plan, users will experience a good, or positive, trip. However, most people who have used LSD know that there's always a possibility of having a "bad trip."

It's not really clear what causes a bad trip, especially since each trip can be very different depending on the person. LSD users sometimes say that it's due to the "set and setting." This means that if you are already in a bad mood, or you trip in a highly structured environment that requires you to think logically (such as school), you could have a bad trip. This may include losing sight of the illusory aspect of tripping, which results in fear and paranoia, and a feeling of dying of being in hell. The loss of control is frightening, and it seems like the trip will never end [source: Davis].

Sometimes when someone has a bad trip, they wind up in the emergency room of a hospital, but there usually isn't much that doctors do other than give the person a quiet space and reassurance. They may administer an anti-anxiety medication or a mild tranquilizer to ease the patient's panic. As the trip ends, the patient may feel dizzy or nauseous, but people usually recover with no lasting side effects.

For some, one bad trip is enough to swear off LSD forever. Even if LSD users don't have a bad trip, heavy use of LSD can still cause serious mental and physical health issues.

Researchers aren't 100 percent sure what LSD does in the central nervous system, or exactly how it causes those hallucinogenic effects. This is in part because there have never been scientific research studies on how LSD affects the brain. It's believed that LSD works similarly to serotonin, a neurotransmitter responsible for regulating moods, appetite, muscle control, sexuality, sleep and sensory perception. LSD seems to alter the way the brain's serotonin's receptors work. It may inhibit neurotransmission, stimulate it, or both. It also affects the way that the retinas process information and conduct that information to the brain.

As little as 0.25 micrograms of LSD per 2.2 pounds (about 1 kilogram) of body weight causes trips, and that's a fairly standard modern dose. In the 1960s, users commonly ingested four times as much. When a person takes LSD, it's quickly metabolized in the <a>liver and eventually excreted in the urine. A small amount is left in the body by the end of the trip and is probably gone entirely a few weeks afterward.

A common urban legend maintains that LSD stays in the body forever, in minuscule amounts in the brain or spinal fluid. People who believe this say that the brain stores and releases molecules of LSD over time, and this is what causes flashbacks. A flashback occurs when a person who has used LSD in the past has an experience, lasting anywhere from seconds to hours, similar to that of an actual trip. Some LSD users enjoy them and consider them "free trips," while others find them incredibly unsettling.

Most users don't experience flashbacks, and some people claim that they don't really exist, making the subject a controversial one. A study found no link between using psychedelics and experiencing flashbacks. Nevertheless, some psychiatrists say some of their patients report this experience [source: Ferro].

Among people who have reported experiencing flashbacks, many are also mentally ill. Some doctors suggest that what the user perceives as a flashback is really a form of psychosis or mental illness that may have emerged due to LSD use. There's a medically recognized disorder called Hallucinogen Persisting Perceptive Disorder (HPPD), in which some people who have taken a lot of LSD experience persistent visual hallucinations (as opposed to the brief flashbacks). It's not yet known exactly what makes some people more susceptible to these experiences than others.

On the next page, we'll look at worst-case scenarios.

Very few reports pinpoint LSD as a cause of permanent health problems or death. That's not to say that there haven't been scary situations involving the drug. In 1974, The Western Journal of Medicine reported an instance in which eight people snorted multiple milligrams of LSD at a party thinking that the substance was cocaine.

Most of them passed out. In the hospital, they suffered from fevers, vomiting and internal bleeding. However, all of the patients recovered within 12 hours with no lasting effects. Five of them were examined regularly for a year afterwards for long-term problems.

For decades, LSD has been potentially linked to other health problems. There have been reports of heart attacks, strokes and other deaths associated with LSD use, but many of these users also had other recreational drugs in their systems, so the role of LSD was inconclusive.

The real physical damage associated with LSD comes from what can happen when someone loses inhibitions and has poor judgment, skewed perceptions or a sense of immortality while tripping. LSD users have accidentally killed themselves by walking in front of a car, falling from windows or buildings, or by making the mistake of driving while altered.

These people didn't "go crazy." LSD isn't likely to make someone go insane or become psychotic. It can interact with other drugs and cause psychotic symptoms (especially other drugs that work on neurotransmitters). Some people with histories of certain mental illnesses, such as schizophrenia or psychosis, may have their symptoms exacerbated on LSD. In susceptible subjects, it may also speed the onset of these illnesses.

Heavy LSD users can also develop profound social problems, completely ruin their sleep cycles, and lose interest in eating and personal hygiene. They become uninterested in participating in the world going on around them and feel completely disconnected from everybody else. The real problem is that because they're taking LSD so often, they think the LSD is creating the illusion that their life is a mess instead of recognizing that it really is a mess.

You won't typically hear about someone being in rehab for LSD abuse, because it's not perceived as an addictive drug. Using LSD for just a few days in a row can cause a person to build up a tolerance quickly, so it's rarely used more than once a week. A person who uses LSD twice a week is considered a heavy user. In addition, repeated trips tend to lose their novelty, and what once seemed magical becomes every day and commonplace. The effects caused by LSD aren't dependable in the way that other drugs' effects are -- you never know how you'll feel or what you'll see. That's why most addicts crave the dependable nature of drugs like heroin, cocaine, methamphetamine, and the like.

Next, let's take a look at LSD that's used for purposes other than recreation.

Before it was a recreational drug, LSD was used in psychiatric therapy. In the beginning, psychiatrists hoped that LSD would prove to be a cure for some forms of mental illness. It was thought that giving a patient LSD would remove the need for years of psychotherapy and bring about permanent changes in behavior and personality. Between 1950 and 1965, approximately 40,000 patients consumed Sandoz's Delysid tablets [source: Henderson]. These included schizophrenics, obsessive-compulsives, depressives and autistic people. It was also administered to people considered mentally ill with sexual perversions, such as homosexuality.

There were two main types of therapy that incorporated LSD usage. In Europe, psycholitic therapy was common. Psychiatrists gave patients low doses of LSD (50 micrograms or less) over several sessions and encouraged them to focus on their childhood and subconscious. American psychiatrists were more likely to use psychedelic therapy. They gave their patients high doses of about 200 micrograms over just a few sessions. Instead of bringing out childhood memories, these doctors hoped the high doses of LSD would elicit a positive spiritual awakening and encourage patients to find meaning in their lives and want to better themselves.

The spiritual awakening approach was also used on alcoholics, who were difficult to treat through other types of therapy. Some psychiatrists attempted to induce a form of delirium tremens, which might scare alcoholics into reforming themselves. LSD was also given to criminals in the hopes that they could be reformed. Although many psychiatrists reported good results, there were few large studies. The small-scale studies are often considered flawed today because they didn't employ controls.

Sandoz recommended very specific doses of LSD and stated it should only be administered by a psychiatrist in a controlled medical setting. Of course, there was a black market for the drug by 1962. As recreational use grew, the federal government became increasingly concerned about LSD's effects and took steps to restrict its official use. By 1965, very few researchers in the United States were still allowed to possess LSD. There were only six projects conducted in 1969, and by 1974, the National Institutes for Mental Health (NIMH) declared that LSD had no real therapeutic value.

In the 1980s, a team of researchers believed that LSD could be beneficial to terminally ill patients because it helped them to stay aware of their surroundings, relieved their pain and made them feel more connected to their families. The study ended, however, before it really resulted in concrete findings.

In the 2010s, there's been a resurgence in LSD studies for a variety of mental health applications. Psychotherapists are revisiting LSD as an assistive chemical meant to boost patients' abilities to address trauma, depression, and other maladies. Other researchers see LSD has a key to alleviating the emotional strife for people who are struggling with terminal illnesses and end-of-life emotional stress. Two other studies found that the wellbeing brought on a by a single dose of psilocybin (magic mushroom, a naturally occurring hallucinogenic, with similar effects to LSD) persisted six months in 80 percent of the cases [sources: Nature, Feilding].

LSD played an important part in the 1960s counterculture movement. As use spread from research projects at universities to the street, LSD was credited with expanding the minds of young people who were disillusioned with the status quo. A number of LSD pioneers helped spread the news and encourage acid experimentation.

Dr. Timothy Leary was a psychology professor at Harvard when he first tried psilocybin mushrooms in 1960. He was so changed by the experience that he and his Harvard colleague Richard Alpert founded a study to test the effects of psychedelic drugs. Leary believed that they could treat a host of mental illnesses and profoundly change those who took them. Complaints from parents and others, however, led Harvard to fire Leary in 1963.

In 1964, Leary co-authored a book about psychedelic drugs and, the following year, he founded the League for Spiritual Discovery. This was a religion that claimed LSD as a holy sacrament that must be kept legal for religious freedom. Leary toured the country with a presentation that attempted to demonstrate the experience of tripping. He spoke the phrase that came to exemplify the LSD movement, "turn on, tune in, drop out," during a 1967 speech in San Francisco before 30,000 hippies. Leary later stated in his biography that "'turn on' meant to go within to activate your neural and genetic equipment [...] 'Tune in' meant interact harmoniously with the world around you [...] 'Drop out' meant self-reliance" He was disappointed that people thought he meant "Get stoned and abandon all constructive activity" [source: Leary].

Ken Kesey was an author whose first experience with LSD came when he volunteered in 1959 to take part in a CIA study of the effects of psychedelic drugs. He and his friends, known as The Merry Pranksters, traveled across the country, while on acid, in a school bus called "Furthur" as a social experiment. Their adventures were documented by author Tom Wolfe in "The Electric Kool-Aid Acid Test."

While Leary originally advocated a more serious, controlled use of LSD, Kesey was an "acid populist" who believed that if enough people used it, society as a whole could be transformed. In 1965, he began holding psychedelic parties advertised with signs that read "Can you pass the acid test?" Kesey believed that the acid tests expanded consciousness and started a revolution.

Owsley Stanley was a self-taught chemist who helped to make LSD popular and accessible in the influential Haight-Ashbury section of San Francisco. While a student at the University of California at Berkley, Stanley tried LSD but was frustrated with the wide differences in quality and purity. He set up his own lab to make pure, high-quality LSD, which became known as "Owsley LSD" or simply "Owsley." It became the standard by which other LSD was measured after Sandoz stopped making the drug and it became illegal. He often distributed it freely, and it has been estimated that Stanley made half a kilo of LSD, enough for 10 million 50-microgram trips, in his lifetime. He also created an LSD synthesis that was 99 percent pure called White Lightning, as well as another psychedelic drug, STP.

Stanley also became friends with the band the Grateful Dead (who performed at Kesey's acid tests) and worked as their sound engineer. He not only heavily influenced the band's sound, but also designed their Lightning Bolt Skull logo and was the inspiration for the Dancing Bears logo because of his nickname, "The Bear."

In the United States today, LSD is a Schedule I controlled substance under the Controlled Substances Act (CSA). This means that the federal government believes LSD to have high abuse potential, a lack of accepted safe use when taken under medical supervision, and no current medical use. The last criterion is important; LSD is a Schedule I drug, but cocaine is Schedule II due to some medical use (such as local anesthesia). There are higher legal ramifications, in other words, for LSD than for cocaine.

The federal penalty for the first offense of LSD possession is a maximum of one year in prison or a minimum fine of $1,000. Additional offenses can raise the prison time to as much as three years.

The penalties for making or selling LSD are based not only on the number of offenses, but the amount involved. So even if it's the first offense, if the amount is up to 10 grams, the offender can spend five to 40 years in jail and face a fine of $2 million. Higher amounts can result in a life sentence. A 1991 Supreme Court ruling found that when weighing blotter acid, the weight of the paper can be included. Since the actual amount of LSD in the paper is so minute, some people have claimed that this results in unfairly harsh sentences. Regardless of the amount or intent, it's worth remembering this – possession of any amount of LSD is a felony, no matter where you are. Penalties vary on a personal's prior record and individual story.

And who are these LSD users? The 2017 National Household Survey on Drug Use & Health groups LSD users with those who use other hallucinogenic drugs like ecstasy, peyote and PCP. Among their findings:

As in the 1960s, LSD is once again finding traction among younger crowds. After a steady decline in the late '90s and early 2000s, acid consumption jumped 40 percent between 2013 and 2015 in the college-age American population. In some areas, it's a fairly common substance, and in others much harder to obtain [source: Kruzman].

As it stands, acid is still a fringe substance, one with far fewer users than drugs like marijuana, heroin, cocaine, and methamphetamine. But, it's now fashionable for recreational users to "microdose" acid. In microdosing, people ingest tiny amounts of the drug to spark creativity and alter their perceptions, without the time commitment or aftereffects of a full-blown trip. Some say it sharpens their mental clarity and provides startling focus. In the 1990s, Albert Hoffman, the LSD pioneer, took microdoses to help his thinking [source: The Verge].

Whether LSD will reemerge has a major force in drug culture remains to be seen. With harsh federal penalties still in place, researchers (particularly in America) will find their studies thwarted, and recreational buyers and sellers will find themselves wary of prosecution.