From ... in Science Psychedelics — Jul 17, 2019

LSD Guide: Effects, Common Uses, Safety

The invention of lysergic acid diethylamide, known as LSD, changed what the scientific and psychiatric community thought about the roots of mental illness.

When scientist Albert Hofmann first synthesized LSD in 1938 however he recognized that the LSD molecule was similar to serotonin, which had only been identified a few years prior. As a result, scientists began to theorize that chemical imbalances resulted in mental illness. This spawned the development of a new branch of psychopharmacology. LSD entered into popular culture as a recreational drug in the 1950s and 1960s. Though its mainstream appearance resulted in a flourishing of art and culture, the government misinformed the public and perpetuated a false image of LSD in order to target and incarcerate hippies, Black Americans, and other minority groups. This resulted in its harsh prohibition, which also blocked scientists from conducting further research into the medicinal properties of LSD. Its short-lived emergence into popular culture however had an enduring impact on thought, science, arts and culture that can still be felt today. In recent years, studies are being conducted on LSD to evaluate its therapeutic and spiritual benefits. Lysergic acid diethylamide, better known as LSD or acid, is one of the most famous and controversial psychedelics that exists. In 1938, a Swiss chemist named Albert Hofmann synthesized LSD while participating in a larger research program at the Sandoz Laboratories in Basel, Switzerland. He was studying the ergot fungus in an effort to extract active alkaloids, called Lysergamides, for pharmaceutical use. Within this group of alkaloids, ergotamine is the most dominant, which became the precursor for LSD. At the time, Hofmann was attempting to find a cure for headaches. Five years later Hofmann discovered LSD’s psychedelic properties accidentally. First introduced to the market in 1947 as a psychiatric drug, LSD became popular as a recreational drug in the 1960s, and defined the era. From the hippies, Timothy Leary, The Beatles, Jimi Hendrix, Ken Kesey, and The Grateful Dead, LSD inspired a rich subculture, new creative expression, and a prolific body of art. Despite an FDA ban on researching LSD in 1966, scientists were able to understand the overall mechanisms of how LSD produces its psychedelic effects. To this day, it remains one of the most popular psychedelic for recreational use, and a promising substance in psychotherapeutic research. LSD, or Lysergic Acid Diethylamide, is a psychedelic hallucinogen from the Ergoline family. It is a potent psychedelic that typically takes effect about a half hour after ingestion and induces an experience that lasts anywhere between 8-12 hours. LSD can be microdosed as well. Lysergic Acid Diethylamide is a serotonergic psychedelic.

There are three main serotonergic psychedelic groups: phenethylamines, tryptamines and ergolines. LSD is an ergoline. LSD binds to serotonin receptors in the brain and body.

They are called 5-hydroxytryptamine, or 5-HT receptors, and are found throughout the central and peripheral nervous system. LSD binds to most serotonin receptors except for the 5-HT3 and 5-HT4 receptors. Most of the receptors that LSD binds to however are not affected at a high enough affinity to be activated by the brain.

Therefore they do not impact LSD’s psychoactive effects.

The receptors that do play a role in the effects of LSD are the 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5A, and 5-HT6 receptors, but most importantly the 5-HT2A receptor. Binding to the 5-HT2A receptor causes a cross-activation of the 5-HT2A receptor heteromers which is thought to be the cause of the psychedelic effects that LSD creates. LSD stays bound to the 5-HT2A receptor for an extended period of time which is why its effects last for such a long period of time despite a relatively short half-life. Depending on the way LSD is produced, it can either be a semisynthetic or fully synthetic substance. Firstly, a “synthesis” is a chemical reaction that produces a novel chemical compound from chemical precursors. For example, one of the most basic synthesis is the reaction between hydrogen gas and oxygen gas in the presence of heat to create water. Semisynthesis is a chemical process that uses compounds isolated from natural resources as the starting point to produce a different, novel compound.

The novel compound produced must have distinct chemical and medical properties in order to be considered a semisynthesis. Hofmann formed LSD in this way while he was experimenting with various derivatives of lysergic acid extracted from the ergot fungus. When LSD is made through a semi-synthesis, the alkaloids are extracted from the Ergot fungus, Hawaiian Baby Woodrose seeds, or Morning Glory. (Alkaloids are a group of organic molecules that contain Nitrogen).

The alkaloids are used as a precursor, particularly Lysergic Acid Amide.

The precursor is synthesized into iso-lysergic acid hydrazide then isomerized twice to create active LSD. LSD can also be fully synthetic, meaning fabricated from scratch.

The most common way to create fully synthetic LSD is through reacting diethylamine with activated lysergic acid in the presence of phosphoryl chloride and peptide coupling reagents. Lysergic acid is produced by an enantioselective or stereocontrolled total synthesis for a fully synthetic form of LSD. LSD comes in a variety of forms: liquid, tablet, gummies, crystals, blotter paper, gel tabs, and directly through the skin. Anything with LSD infused into it can vary wildly in dose. This is because LSD is measured in micrograms, so large amounts of LSD fit into small consumables. It is most commonly found in blotter paper with a dose between 30 micrograms to 100 micrograms, however average users cannot confirm the dosage. See our microdosing LSD guide for an in-depth review of dosage guidelines. From top to bottom, this macro dosing chart lists doses from low to heavy. Any dose that is less than or equal to the threshold can be considered a microdose.

The threshold indicates the amount necessary to begin to feel the effects of LSD. Typically, the psychedelic community recommends first time users start with a light dose. Users report that it’s the right amount if you want to engage with other people, and enhance your general enjoyment of life. Common doses tend to induce hallucinations and “visions.” Most users that consume less than 75 micrograms do not report any open eye visuals, or OEVs, unless the person is particularly sensitive to LSD. Strong and heavy doses tend to send the user into, what the community calls, a “transcendental state.” Normally, users go in. Meaning, the experience is more interior and can even result in what’s called an “ego death.” This is when a person looses a sense of a personal identity, and “transcends” the self. In Jungian philosophy, an ego death is defined as “a fundamental transformation of the psyche.” Having an experienced user in the room is a safety precaution. Challenging trips can happen and cause long-term effects, such as hallucinogen-persisting perception disorder or post-traumatic stress disorder. So, most of the psychedelic community recommend having someone with you who can help guide the experience if a challenging trip occurs. An analogue is a chemical compound similar in structure and properties to another compound, but with a different elemental composition.

There are a lot of research chemicals that are analogues to LSD and produce a similar kind of psychedelic experience. In most countries they are legal to buy and consume, but double check your local laws to ensure you are not participating in illegal activity. 1P-LSD and AL-LAD are the most common analogues. 1P-LSD has a slightly higher molecular weight, the mass of a single compound. That means that the dosages will likely need to be slightly higher to produce the same effects. Currently, scientists believe 1P-LSD is metabolized into LSD once ingested. Thus the effects will be nearly identical. AL-LAD tends to have a slightly shorter duration than LSD with similar levels of potency. Users report AL-LAD is not as introspective and has more recreational effects like visuals as opposed to therapeutic effects. Neither of these substances are listed under the United Nations’ Convention on Psychotropic Substances. However, many countries have laws in place that make analogues of illegal substances also illegal. Albert Hofmann first synthesized lysergic acid diethylamide in 1938 at the Sandoz Laboratories of Switzerland. Hofmann was studying the ergot fungus in an effort to extract active alkaloids for pharmaceutical use.

These alkaloids are called Lysergamides. Ergotamine is the most abundant, which became the precursor for LSD. On Hofmann’s 25th combination of various organic molecules with lysergic acid, he created LSD which he named LSD-25 for his own reference. Unfortunately, the molecule showed little to no effect on the animals he was testing on, so he abandoned the project. But in 1943, he decided that the molecule deserved a closer look. While Hofmann was handling the molecule, he accidentally dosed himself through his fingertips. Upon beginning to feel the effects, he asked his assistant to escort him home on their bicycles. Once he arrived home he called a house doctor to check his vitals due to the strange changes in perception he was experiencing after his accidental dosage of LSD. His doctor did not find any effects to his vitals aside from his extremely dilated pupils. Because of his bike ride home during the very first LSD experience any human had ever experienced, the day became known as “Bicycle Day.” This day is still celebrated every year among the psychedelic community on April 19th. Hofmann may have introduced LSD to the West in the 20th century, but many other ergolines and their derivatives have been ingested for centuries. For example, Hofmann was experimenting with the ergot fungus in his laboratory. Ergot fungus is a fungi that contains lysergic acid, which became one of the key ingredients in LSD.

The ergot fungus however has an ancient history. Assyrian tablets dating as far back as 600 B.C.E. describe ergot as a “noxious pustule in the ear of wheat,” because it infects rye and other related plants. When ingested, ergot causes a condition called “ergotism.” In the Middle Ages especially, there were major outbreaks of ergotism that swept across towns. Whole populations experienced hallucinations, fever, and occasionally death. One case affected as many as 40,000 people within southern France in 994. It turned peoples’ limbs black making it look like they were in a fire. This in turn made them refer to this poisoning as a “holy fire.” Recently, another discovery of ergot poisoning in 1692 opened a whole new theory about the infamous Salem Witch Hunt. Now there is speculation that ergot might have been the real culprit, not the devil or magic spells.

The people of Salem might have been hallucinating from ergotism the entire time. Aside from Lysergic Acid, another LSD precursor is Lysergic Acid Amide, which possesses its own set of psychoactive properties.

The usage of Lysergic Acid Amine traces back to the Vedas, the most ancient of Hindu scriptures. Furthermore, Lysergic Acid Amide was used in an Ayurvedic medicinal treatment for erectile dysfunction and syphilis. Ayurvedic medicine is one of the oldest forms of holistic healing developed over 3,000 years ago in India.

The primary goal of Ayurveda is to promote overall health to prevent illness instead of treating individual ailments. A decade after Hofmann accidentally dosed himself with LSD, the CIA became aware of LSD’s unusual and powerful effects.

The CIA initiated the “MK-Ultra” project to experiment with LSD as a mind controlling tool for the purposes of the U.S. government. SubProjects within MK-Ultra also investigated hypnosis, neurosurgery, electroshock, torture, sexual blackmail, stage magic, and poison .

The CIA dosed unsuspecting civilians with LSD for almost a decade (1955-1964).

The US government also funded research to investigate the potential use of LSD as a chemical weapon. Regardless, MK-Ultra dropped its efforts in 1964. Subsequently, the records were destroyed in 1972. Finally, the New York Times exposed the truth in 1974. This led to the Senate calling for an immediate inquiry into the U.S. Intelligence’s abuse of power.

Then, journalist John Marks continued to uncover more files. In response, President Ford issued executive order 11905 as an attempt to stop human testing without consent despite it already being in violation of the Nuremberg Code. Celebrated writer Ken Kesey was first exposed to psychedelics as a creative writing student at Stanford. He participated in government research program that was administering LSD, psilocybin, mescaline, and DMT.

The experience changed his life. Shortly afterwards, he completed his first and seminal novel, One Flew Over the Cuckoo’s Nest. “I been silent so long now it’s gonna roar out of me like floodwaters...” –One’s Flew Over the Cuckoo’s Nest In the 1960’s Kesey was throwing a series of parties that became known as “acid tests” with his crew, “The Merry Pranksters.” They traveled in a psychedelically painted school bus named “Further.” Further became an icon for the hippie movement. In 1964, they took Further out West.

They crossed paths with other notable psychonauts such as Allen Ginsberg, Timothy Leary, Ram Dass, and Jack Kerouac. Tom Wolfe would later write a book that immortalized their LSD fueled bus trip titled The Electric Kool-Aid Acid Test. “Everybody, everybody everywhere, has his own movie going, his own scenario, and everybody is acting his movie out like mad, only most people don’t know that is what they’re trapped by, their little script.” – The Electric Kool-Aid Acid Test LSD strongly impacted the music of The Beatles and The Grateful Dead. John and George from The Beatles were first introduced to LSD at a dinner party. A dentist had dosed them with it in their coffee. At the time neither one of them knew much, if anything, about LSD and what its effects were.

They went on to go to a night club and thoroughly enjoyed their experience. Afterwards they shared it with the rest of The Beatles and it began to further shape their music. Paul McCartney claims their hit song “Lucy in the Sky with Diamonds” is entirely about LSD as well as “A Day In The Life.” This led to the BBC permanently banning these songs from broadcasting on their station.

The Grateful Dead regularly used LSD and it strongly influenced their music. However, the bands use of LSD does not stop at the performers.

Their sound engineer, Owsley Stanley, known as “Bear,” was also a frequent user of LSD and a chemist. He helped finance The Grateful Dead’s beginning with his profits from making and selling LSD. His LSD business was extremely successful despite it being illegal, and he is largely credited with being one of the first people to mass produce the substance. Within a two year stretch of time he produced over five million doses of LSD. His professional name “Bear” is also where the famous Grateful Dead bears stem from. In 1959, Timothy Leary had garnered a reputation as an esteemed personality, researcher, LSD advocate, and as a Harvard professor. He personally used LSD fairly regularly and created many of the catchphrases associated with psychedelic safety still used today. He was the first to emphasize the importance of “set and setting” when using psychedelics. This concept is still heavily influential within the psychedelic community. In 1962 he established the International Federation for Internal Freedom, or IFIF, along with Richard Alpert.

The objective of this organization was to study the effects of regularly using psychedelics and publishing these results to the public. He enlisted Lisa Bieberman to help distribute his findings in a journal called the “Psychedelic Review.” Bieberman was a friend of Leary and ran a sort of psychedelic information center from her own home.

The negative backlash about LSD in America did not deter Leary, or keep him quiet. In fact, he declared openly that he planned to administer LSD to four million people. Leary’s famous slogan— “turn on, tune in, drop out”— sent a message far and wide that psychedelics were for everyone. That did not please the government. Harvard fired Leary and Alpert soon after. Leary continued to fuel the growing political fire by telling the government that “...the kids who take LSD aren’t going to fight in your wars.” After Leary’s exit from Harvard, the rate of recreational use of LSD increased among youngsters. However, they knew nothing about “mindset and setting” causing the rate of “challenging trips” to dramatically increase, which blistered LSD’s reputation. Some people did have psychotic breaks, but mostly those who had a family history of schizophrenia. Most people who ended up in the hospital were experiencing hallucinations, not psychotic breaks.

The doctors misinterpreted their panic as psychosis. Thus, the misunderstanding surrounding LSD also contributed to the downfall of its reputation. Currently, multiple studies are being conducted on the neuroscience behind LSD in the U.S. and abroad. At John Hopkins University, renowned professor and psychonaut Roland R. Griffiths is comparing naturally occurring “God encounter” experiences and those provoked by psychedelics, such as psilocybin, LSD, ayahuasca, and DMT. He found striking similarities between these groups with most participants having vivid memories of communicating with some form of a conscious, benevolent, intelligent, sacred, eternal, and all-knowing being.

These respondents largely reported the event as their most meaningful personal and spiritual experience. Further, two-thirds of participants who identified as atheists prior to the event did not identify as atheists afterwards. Other studies are gauging the value of LSD-assisted psychotherapy and its potential benefits in reducing anxiety and catalyzing spiritual/mystical experiences.

The Multidisciplinary Association for Psychedelic Studies (MAPS) just completed the first double-blind study on LSD’s potential for therapeutic use. With 12 subjects, they found a reduction in anxiety after two sessions of LSD assisted psychotherapy. While 12 subjects is not enough to confirm any results, it is shedding light on the potential therapeutic benefits of LSD. Today LSD is better understood, but the media is still perpetuating misconceptions. A study conducted by the Washington University on brain activity while under the effects of LSD use clearly concluded alterations in brain blood flow, electrical activity, and network communication patterns.

The study showed an increase in brain blood flow, but overall lowered electrical activity and network communication patterns. Despite these clear conclusions, The Guardian and CNN published articles stating the brain is “much more active” while under the effects of LSD. This is just one example of mainstream media twisting scientific studies to fit their narrative.

The new, early Human trials are showing the benefits of LSD in treating Alzheimer’s disease. This study only dabbled in a single microdose VS placebo and shown that there are no problems with the safety of this method. It is also effectively shown that LSD does affect the places in the brain that are affected by Alzheimer’s disease.

The second phase of the trials is needed to see how broad the application on patience can be with many different variables. Yes. LSD is a Schedule I substance under the Controlled Substances Act. This means LSD is illegal to manufacture, buy, possess, and distribute without a license from the DEA. By categorizing lysergic acid diethylamide as a Schedule I substance, the DEA believes that LSD meets the following three criteria: having a high potential for abuse, no legitimate medical use in treatment, and a lack of accepted safety laws for its use under medical supervision. Many psychedelic communities in America are currently working to change its legal status.

The US increased the penalties related to the unlawful act of having or consuming LSD on October 24th, 1968 by Public Law 90-639. Even though Mexico regulates LSD, they passed a law in 2009 that legalized the possession of 15 micrograms of LSD. Portugal decriminalized LSD in 2001. Possession of less than 500 ug is not regarded as a criminal offense, but the substance can still be seized and the possessor may be referred to mandatory treatment. Before we can discuss whether or not LSD is toxic, we first need to define what makes a substance toxic. Toxicity is defined based on the levels of exposure required for a substance to cause harm to a human or animal.

The level of toxicity is measured based on the dose required to cause harm to a human. Even water can be toxic in too high of a dose and lethal snake venom can be non-toxic in a small enough dose. LD50 is a common measurement of toxicity, which measures the lethal dose for half of the tested organisms. Multiple studies have shown that there isn’t any risk of toxicity when consuming pure LSD. To human beings, the lethal dose of LSD is unknown. In some animals, such as rats, the LD50 is 16,5mg/kg. That means a person that weighs 75kg would have to consume 1,2375g or 1.237.500μg of lysergic acid diethylamide. That equates to about 12,000 strong doses of this very potent compound. Studies performed on monkeys also suggested no risk of toxicity. Scientists injected Monkeys with doses as high as 1mg/kg i.v. and did not find any lasting somatic effects. For a human being, the equivalent dose would be up to 700 common doses of LSD. Cumulative effects on the body are a different story.

There are concerns that prolonged exposure to LSD can impact the heart, since there are serotonin receptors on the heart. This is still up for debate. Currently, there isn’t any reliable evidence that either confirms or denies the long-term effects of LSD on the heart.

There are two categories of interactions: Unintentional and Intentional An unintentional interaction is mixing psychedelics and ergolines with medications, or if there is a preexisting medical condition. It is not recommended to mix LSD with prescription medications. In particular, Benzodiazepine tends to lower the effectiveness of lysergic acid diethylabamide or any other psychedelic substance. Mixing certain antidepressants with LSD can result in serotonin syndrome due to an overload of serotonin in the central nervous system. An intentional interaction is the mixing of two plant-based or synthesized substances. Substances that can be taken with LSD are called “flips.” Interactions also have their own names.

The most popular flip is a “candy flip,” which is the combination of LSD and MDMA. A “hippie flip” refers to a mixing psilocybin and LSD. A “Jedi flip” is a mixture of psilocybin mushrooms, LSD and MDMA. All of these “flips” create a psychedelic effect that is fairly unique and unlike either of the substances by themselves. This is thought to be from the synergistic properties when consuming both substances together. For a more thorough list of interactions, consult the image below by Tripsit: There isn’t substantial data to suggest that LSD can be fatal in healthy adults. In babies and small animals, substances are problematic due to the risk of vasoconstriction. Vasoconstriction is a phenomena where the blood vessels contract. In extreme cases, such as ergotism, people have lost fingers and extremities. According to David Nutts study on the dangers of popular drugs, LSD is less harmful than most popular drugs, such as alcohol, benzodiazepines and cocaine. However, LSD could trigger psychosis in those who are predisposed to this condition. Psychosis is a risk when taking most drugs, including alcohol. If there is a history of mental illness in the family, such as schizophrenic disorders, consult with a psychiatrist before engaging with any substance. Other concerns include HPPD and PTSD. HPPD, or hallucinogen persisting perception disorder, is a disorder where users see “visual snow” long after the trip has ended. This can disrupt an individual’s ability to perform regular tasks due to the distraction caused by visual snow. In more extreme cases HPPD can result in severe hallucinations for prolonged periods of time. LSD can stay in your system for up to four days after use. Typically, it takes about thirty minutes to begin feeling the effects.

The peak tends to occur three to four hours after the onset. A normal trip lasts roughly twelve hours.

The most common way for measuring a dosage of LSD is by the number of micrograms. 50-150 micrograms is typically a standard dose that produces psychedelic effects. Taking more than the standard dose can cause an LSD overdose, which has mixed reported reactions.

There are many ways to make LSD, but the most common way is by extracting ergotamine or LSA to use as a precursor to making LSD.

The precursor is synthesized into iso-lysergic acid hydrazide, then isomerized to create iso-lysergic diethylamide. This compound is then isomerized again to create active LSD.

The simplest and most common way of taking LSD is ingesting a piece of blotter paper infused with LSD. It can also be absorbed through the skin, ingested from a solution, or injected intravenously. Pure LSD in its solid form is a white crystal or powder. However, it is very uncommon to find LSD in its pure solid form. A solution of LSD will only have the appearance of the solvent used giving it no discernible appearance. If infused into a piece of blotter paper or any other consumable, it will also make no impact on the way that blotter paper or consumable appears. Albert Hofmann first synthesized LSD in 1938. Hofmann discovered its psychedelic effects in 1943. He was re-examining the substance looking for any potential pharmaceutical uses, and accidentally dosed himself. LSD degrades with time in the presence of light, moisture and heat. Yes. “LSD” is an acronym for “lysergic acid diethylamide”. Contributor | Cort Honey This LSD guide is for educational purposes only. While it is our belief that choosing to consume psychedelics is an inalienable human right, many psychedelic substances are currently illegal in the United States. Our substance guides provide the public with the most accurate and reliable information about psychedelic substances that currently exist. We have compiled research, scientific studies as well as experiences and thoughts from the psychedelic community. We do not include all the scientific research and studies. Rather, we curate each our guides to reflect the most relevant insight backed by the most credible evidence. That being said, we are just at the beginning of studying these substances. Everyday we are learning something new. Knowledge is power! Have a bite. If you have relevant information or updates concerning the research and studies of psychedelic substances, please reach out to [email protected]. We appreciate your contribution. –RS.

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