LSD: The Chemistry, Effects, and Brain Science

LSD Science
By Tessa Eskin

It was the spring of 1943. Albert Hofmann was in his lab, revisiting a shelved research project on the ergot fungus. He was on the hunt for a compound to stimulate the respiratory and circulatory systems. Ergot had an extensive history, from its use in ancient Greek rites to the Middle Ages, when it was used by midwives to hasten and ease childbirth. The practice was abandoned in the 19th century, as it risked endangering the babies. But that day, Hofmann followed a hunch that would lead to a discovery no one could have predicted. Later, he would tell his friends, “I did not choose LSD; LSD found and called me.”

A strange feeling came over Hoffman after making accidental contact with the compound, compelling him to leave work and head home. That afternoon, he experienced the first human acid trip in history, unknowingly launching the zeitgeist of the mid-20th century. Lysergic acid diethylamide would claim many whimsical names, from California Sunshine to Electric Kool-Aid. It spread from pharmaceutical laboratories to psychiatry circles, where researchers explored its potential to explore the subconscious mind. In the 1950s, the CIA explored its use in Project MK-Ultra, their notorious mind control program. LSD then rippled out into the counterculture, influencing music, social change, and the collective imagination for decades to come.

The World Formed Anew  

LSD is odorless, tasteless, colorless, and extremely potent. Users ingest it orally in minuscule doses, and it takes effect within an hour. The trip itself lasts from 8 to 12 hours, with a peak halfway through. Generally, LSD dilates the pupils, increases blood pressure, and warms body temperature. Some feel a slight tingling and drowsiness. At the onset, one might find themselves contemplating a simple everyday object as if seeing it for the first time. The effect is very much as if one has returned to their childhood perception, when the world felt entirely new. Then there are the optical effects…

LSD doesn’t exactly cause hallucinations. Rather it enhances perception of our real environment, causing optical illusions and visual effects. Colors brighten, textures undulate, and visual details deepen in complexity and symbolism, inviting a closer look. The trip is euphoric, the world seen anew through a magical filter. Many encounter poignant emotion, or surrender to pure joy and laughter. The boundaries of the mind have shifted, and new patterns stretch out, mapping an internal narrative or mythology. In the right setting, LSD induces a sense of oneness and unity with the earth, among people, and the entire cosmos.

How It Works

LSD interacts with serotonin, the chemical messenger of the brain, specifically through the 5-HT2AR receptor. The neurotransmitters regulate mood, appetite, sleep, sexuality, sensory perception, and muscle control. Researchers are still investigating LSD’s effect on the central nervous system, but believe it inhibits or stimulates neurotransmission — or does both.

A study at the University of North Carolina used crystallography to explore the structure of LSD when bound to serotonin receptors. They found that part of this 2B receptor acts as a lid, wrapping around the LSD molecule and trapping it. This may explain why the effects take so long to set in, and why the trip is prolonged. LSD stays in the blood system for a few weeks, leaving a peaceful afterglow and the occasional lingering optical effect.

What Is It Good For? Medicinal and Therapeutic Benefits

Since the 1950s, there has been much hope for LSD’s potential use in psychiatric therapy. The War on Drugs interrupted these studies during the 1970s, casting the field in a cloak of stigma. Over the last decade, though, fresh interest in innovative mental health treatments has revived scientific interest. There is a renewed focus on alcoholism (picking up from the mid-century where it left off), but this is merely the tip of the iceberg. A new frontier is set before us, with the potential to treat trauma, depression, and a range of mental disorders. Most promising is the use of LSD to soothe the end-of-life anxiety felt by those suffering terminal illnesses. LSD has also been used successfully to treat cluster headaches, resulting in diminished symptoms. 

Misconceptions

Although LSD has somewhat recovered from years of stigmatization, there are still concerns that must be addressed. These are derived from the misinformation and propaganda spread during the War on Drugs. Classed as a Schedule 1 drug, LSD is still viewed as addictive and a danger to the self and society.

Firstly, LSD is not addictive. The effects will never be uniform, making it difficult to build dependency as one might with heroin, cocaine, or methamphetamine. It rarely triggers compulsive drug-seeking behaviors and induces no physical cravings for more. We also build a quick tolerance to LSD, meaning that to really enjoy its benefits, it must be used rarely. Many users feel satisfied by one trip and are happy to take a long break to process the experience over time.

Drugs ordered by their overall harm scores, showing the overall scores of harms to users and harm to others Nutt, D., King, L., Phillips, L., & Independent Scientific Committee on Drugs (2010)

Some are concerned about “flashbacks”, but these are quite rare, and often manifest as a slight hint of the full experience. At times, colors may seem brighter and music more visceral, but the media has highly exaggerated the “danger” of this phenomenon. 

Another misconception is that LSD can trigger psychosis or make people “crazy”. This is only the case if LSD interacts poorly with other drugs, or if users have a history of schizophrenia or psychosis. If there are underlying illnesses, the trip might exacerbate symptoms, but this is extremely rare. As far as we know, LSD itself has never directly caused a fatality, but some have suffered accidents from poor judgment or reckless behavior.

The science is still catching up from decades of stigmatization, but it’s clear that LSD can be highly beneficial when taken in a controlled setting. It has huge potential, especially within a therapeutic environment. The more we know about LSD, the sooner we can break the stigma and finally ease the suffering of those dealing with mental illness.