The Science Behind LSD

Jessica Clifton

by Jessica Clifton

25th March 2020

The artistic subculture inspired or even fuelled by LSD (lysergic acid diethylamide) is well-documented, but how about the science behind LSD? How and where did the drug originate? How does LSD work and how does it affect people? We’ll be answering those questions in this article.

Arguably, LSD is one of the defining drugs that influenced music, visual arts, and popular culture in the 1960s. It was the era in which the so-called psychedelic culture was born, epitomised by tie-dye shirts and psychedelic rock music.

What is the origin of LSD?

Even though LSD is used as a recreational drug, it was originally developed by scientists to create new medicines.

A chemist employed by Sandoz Pharmaceutical, Albert Hofmann, synthesised LSD in 1938 while researching a blood stimulant. The hallucinogenic side-effects of the drug were discovered in 1943 when Hoffman accidentally ingested some LSD.

What led to LSD abuse?

As little as 25 milligrams of LSD is sufficient to induce vivid hallucinations. Ironically, some scientists, physicians, and psychologists were responsible for opening the floodgates of substance abuse for LSD.

For example, Harvard psychologist Timothy Leary promoted LSD and other similar psychedelic drugs. He was later arrested, charged, and imprisoned for drug-related crimes.

Because of the neurochemical effects of LSD, psychiatrists conducted many experiments between the 1940s and 1960s, using LSD in their attempt to uncover therapeutic and medical uses for the drug. They failed from that respect, not discovering any medicinal effect of LSD, and the free samples from Sandoz Pharmaceuticals led to substance abuse.

The demand fuelled the illicit manufacture of LSD worldwide. According to a report based on the National Household Survey on Drug Abuse, around 20.2 million Americans aged 12 years old and above have used LSD at least once in their life.

What does the drug LSD stand for?

LSD is an acronym for its chemical name, lysergic acid diethylamide. The name is indicative of how the compound is formed from the reactions of two compounds. It is more popularly known by other colourful names such as acid, blotter, California sunshine, dots, and Electric Kool-Aid.

The two compounds necessary for synthesising LSD are in the name itself. It is synthesised from the formal condensation of lysergic acid with diethylamine. It is a type of alkaloid that is derived from the ergot fungi group of the genus Claviceps.

Many species of mushrooms under the genus Claviceps have hallucinogenic properties. The lysergic acid component of LSD is derived from the alkaline hydrolysis of lysergamide compounds from Claviceps purpurea and other related mushrooms. Lysergic acid reacts with diethylamine by activating the acid using phosphoryl chloride and peptide coupling reagents.

LSD chemical structure

LSD is a complex compound with the chemical formula C20H25N3O and a molecular weight of 323.4 g/mol.

The chemical structure of LSD

The International Nonproprietary Name (INN) for LSD is lysergide. The International Union of Pure and Applied Chemistry (IUPAC) name for LSD is somewhat of a mouthful: 


The IUPAC name is the more accurate and precise name because it describes the molecular components and their positions. LSD has the following molecular functional groups:

  • Carboxylic acid group – the group that contains double-bonded oxygen
  • Primary amine group – the first group that contains nitrogen
  • Secondary amine group – the second group that contains nitrogen

Meanwhile, the following are indicated in the IUPAC name:

  • The positions of the functional groups
  • The types of functional groups
  • The longest, continuous carbon chain
  • The number of carbons in the longest chain
  • The branched groups

The molecular structure and the functional groups of LSD determine how the molecule reacts with other chemicals and how it binds with the receptors of brain cells.

How does LSD work?

LSD is a powerful hallucinogenic drug that changes brain chemistry. It triggers hallucinations because it interrupts the normal functions of neurotransmissions that interpret sensations. It mimics serotonin, which is a neurotransmitter that regulates the mood and the feeling of wellbeing.

Out of the 14 types of serotonin receptors in the brain, LSD molecules bind with a specific receptor called 5-HT2A. When this happens, sensory perceptions become jumbled.

Mental or abstract images become mixed with perceived images of real objects. Other senses such as smell, hearing, and taste may also be affected. In some cases, a person who takes the drug may experience synaesthesia, a state in which your senses are mixed up. You smell colours or taste sounds, for example.

LSD has psychedelic effects on brain chemistry

LSD has psychedelic effects on brain chemistry

The experience of taking LSD can be truly ‘psychedelic’ because of the confused mixing of sensory perceptions and abstract mind images. Unlike other drugs, LSD is physically non-addictive but it can cause serious and long-term alterations of brain chemistry.

Among the side-effects of taking LSD are:

  • Nausea
  • Hallucinations
  • Increased heart rate
  • Tremors
  • Psychosis
  • Delusions
  • Paranoia
  • Anxiety

Does LSD change your brain chemistry?

Chemically speaking, LSD is similar to some naturally occurring chemicals in the brain, such as serotonin and dopamine. The drug binds with your serotonin receptors, inhibiting the normal actions of this neurochemical.

However, it does not increase dopamine tolerance. Some dopamine pathways in the brain have important roles in reward-motivated behaviours. Some addictive drugs like meth suppress dopamine and increase dopamine tolerance. As a result, a person taking such a drug becomes dependent or addicted to the drug. That is not how LSD acts on the brain.

Although the science behind LSD is definite about its non-addictive nature, it can significantly change the brain chemistry and potentially the brain structure itself.

According to a 2018 study, LSD and other psychedelic drugs can increase the number of branches and dendritic spines (small protrusions) on neurons. They also found out that the drugs increased the number of synapses or connections between neurons in the rats that they tested.

If these results also hold true for humans, psychedelic drugs could potentially treat some long-term debilitating neuropsychiatric diseases such as bipolar disorders. The study titled “Psychedelics Promote Structural and Functional Neural Plasticity”, used both live animals and brain specimens. 

Although LSD and other psychedelic drugs remain illegal in many parts of the world, their therapeutic potential may prompt governments to regulate them for medical purposes. Although it probably will still take several decades, many experiments, and animal testing before therapeutic application for humans can be approved.


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