How does LSD work? Nobody actually knows how LSD affects the brain.
LSD is the common name for Lysergic Acid Diethylamide. So, why is it LSD and not LAD? LSD comes from the German Lysergsäurediethylamid. It was synthesized on November 16, 1938 by Albert Hofmann, a Swiss chemist. He was searching for ergot alkaloid derivatives, which can be used to constrict blood vessels, relive migraines, and relieve the conditions of Parkinson’s disease, amongst other things. LSD was the 25th derivative he synthesized, so he originally called it LSD-25. He didn’t pay any attention to what he had found until five years later when he ate 250 ㎍ of it. He was testing all of the drugs he had synthesized to see what they did, and he calculated that 250 ㎍ was a good dose. The LSD had a much stronger effect than he had anticipated.
The company Hofmann worked for, Sandoz Laboratories, began to market the drug as a cure for any psychological ailment from schizophrenia to alcoholism. The CIA began to research the effects of LSD in the 1950s and introduced it to the USA. It quickly became popular and was the main drug of the counterculture. The American government made it illegal in 1968.
LSD is a very potent drug. The 250 ㎍ that Hofmann took is about 10 times higher than the common dose. LSD can have several effects that differ from person to person. It can cause pupil dilation, reduced appetite, sweating, wakefulness, elevated body temperature, blood sugar, and heart rate. It can also cause visual hallucinations, improved mood, joy, euphoria, and a heightened mental state. However, it can also cause fear, anxiety, panic, paranoia, and even suicidal thoughts.
So, why does LSD have these effects? The pharmacology is partly understood, but not completely. LSD binds itself to receptors in the brain. It attaches itself to dopamine receptors and serotonin receptors. Dopamine is a neurotransmitter and the body produces it to send messages between nerve cells. Dopamine is particularly responsible for making us feel pleasure. Serotonin is also a neurotransmitter and is largely responsible for mood, sleep, digestion, sexual desire, bone health, blood clotting, and wound healing.
The LSD enters the dopamine and serotonin receptors and the receptor forms a lid, trapping the LSD inside it. This is one of the reasons why LSD can have effects that last for up to twenty hours. The LSD stays trapped and cannot be cleaned away.
The brain uses serotonin to communicate. It allows us to regulate our moods and control our perception. We use it to interpret what our senses are telling us. The LSD binds to the 5-HT2A serotonin receptor, basically blocking it. The result is that our moods go haywire, causing the euphoria or anxiety, and we cannot control our senses, causing the hallucinations. It is thought that LSD might increase the release of glutamate in the brain. Glutamate is also a neurotransmitter and is responsible for learning and memory. This could be one reason why some people experience flashbacks of acid trips.
LSD is thought to be non-addictive, and tolerance to the drug builds up extremely quickly, although it resets back to the baseline after two weeks. Addiction trials of drugs are often performed with animals and if the animal willingly self-administers the drug being tested, it is considered to be addictive. This doesn’t happen with LSD. It is also difficult to fatally overdose with it. There are records of 8 people having overdosed, and they all survived, admittedly with hospital treatment. However, there are reports of deaths from suicides while people are under the influence of the drug.
There are cases where long-term use of LSD can cause hallucinogen persisting perception disorder. These are generally flashbacks or lasting hallucinations that can have a detrimental effect on the person’s life.
The CIA and Britain’s MI6, notoriously gave LSD to their troops for years to test its effects. They wanted to know if it could be used as a mind control drug or if it had any use during interrogations. MI6 were forced to pay a lot of compensation to their test subjects for the damage they did. The CIA, as far as I can find, only paid out in the case of one person who died after being secretly dosed.
So, LSD generally works by blocking serotonin in the brain and preventing the brain from controlling moods or understanding the input from the senses, causing hallucinations. And this is what I learned today.
Sources
https://en.wikipedia.org/wiki/Lysergic_acid_diethylamide
https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)
https://americanaddictioncenters.org/lsd-abuse/what-does-lsd-do-to-your-brain
https://www.nih.gov/news-events/nih-research-matters/protein-structure-reveals-how-lsd-affects-brain
https://www.webmd.com/mental-health/what-is-dopamine
https://my.clevelandclinic.org/health/articles/22572-serotonin
https://www.health.harvard.edu/mind-and-mood/dopamine-the-pathway-to-pleasure
https://www.theguardian.com/science/2006/feb/25/drugs.thisweekssciencequestions
https://scholarworks.arcadia.edu/cgi/viewcontent.cgi?article=1013&context=senior_theses