LSD’s Effects on the Brain

Paul Austin · January 7th, 2016

One of the biggest concerns around psychedelics is the long-term effects on the brain.

Myths around psychedelic use are rampant.

While LSD has caused long-term insanity in certain individuals, almost all of these cases occurred in people who either had a previous history of mental illness (especially schizophrenia) or who had a latent issue.

LSD does not ‘create’ insanity or mental health issues. Instead, it can, in rare situations, act as an activator of certain mental health issues.

So, if we get past the initial scare of LSD, what are the actual effects of LSD on the brain?

In this article, I will break it down into three parts – the general effects of LSD (basically, the layman’s version of what LSD does to the brain), the science-y breakdown of LSD’s effects, and the possible long-term effects of LSD.



Recently, researchers at the Beckley Foundation began research on the specific effects of LSD on the brain. The research is led by a group of neuroscientists at the Imperial College of London. They raised money for the research through a crowd-funded campaign.

These same researchers previously conducted studies with psilocybin, the primary ingredient in magic mushrooms.

They found psilocybin suppresses activity in certain “hub” areas of the brain that normally play a constraining role.

In suppressing activity in certain areas, psilocybin helps brain regions that are normally distinct begin to communicate with one another, which could be why we see an increase in creativity with the use of this substance.

Beckley’s latest study involved giving 20 volunteers a small dose of LSD and then using MRI and MEG imaging to show how LSD affects brain processes.

What was the primary hypothesis?

The researchers believe LSD may behave in a similar way to psilocybin, reducing blood flow to the control centers of the brain and thus dampening their activity, which ultimately enhances brain connectivity.

In a recent post on the subreddit ‘Explain Like I’m Five’ a Reddit user with the username ‘Gaywallet’, who works as a neurobiologist, gave the following explanation for LSD’s effects on the brain:

“LSD happens to be even better at activating serotonin receptors than serotonin itself, so it essentially increases the normal levels of signaling by serotonin (it does this through a variety of mechanisms, not just limited to better binding – it actually releases extra serotonin, changes the lock to accept keys more readily, etc.).

He then goes on to explain, in simple terms, what the researchers at Beckley Foundation are attempting to prove through research:

“Through a relatively unknown mechanism, LSD increases ‘cross-talk’ between areas of the brain. That is to say, it helps stimulate areas of the brain that don’t normally talk to each other, to start talking to each other. Over the long term, it can even help create connections that previously didn’t exist – much like putting up extra telephone or internet lines. This increased cross-talk while under the influence of LSD (combined with the increased sensory input) often results in something known as synesthesia, or a mixing of the senses.”

(If you want to see the full response, go here)



Let’s get deeper into the other effects of psychedelics, specifically the cognitive processes affected by psychedelics.

The relationship between classic hallucinogens (like LSD and Magic Mushrooms) and the neurotransmitter serotonin has been established in several studies.

When ingested into the human body, LSD acts as 5-HT (Serotonin) autoreceptor inhibitor, thus it is a 5-HT agonist (which is a fancy-schmancy way of saying that LSD, in some way, activates serotonin receptors.

Furthermore, LSD increases the level of active 5-HT molecules by disaffecting their autoreceptors (a safeguard type feature in the brain which reduces levels of certain neurotransmitter sand the like).

There are 15 different serotonin receptors, but LSD specifically activates the 2A subtype (5-HT2A). The HT2A receptor is involved in cognitive processes in the prefrontal cortex.

And this is an important point, for this is where many of LSD’s benefits come from its involvement in the prefrontal cortex.

The prefrontal cortex is thought to be active in planning complex cognitive behavior, personality expression, decision-making, and moderating social behavior.

It also plays a key role in a human’s ability to process information from all other brain systems, and make goal-directed decisions as a result.

If users understand the role of the prefrontal cortex in human thought and compare the urges one has after an excellent psychedelic trip, it makes sense why psychedelics can be such powerful tools for transformative change.

One of the benefits I always experience from a psychedelic trip is an urge to reflect on life and figure out how I can improve it through practical, goal-oriented behavior.

“LSD activates receptors in the prefrontal cortex; thought to be involved in planning complex cognitive behavior, personality expression, decision-making, and moderating social behavior.”



Although scientific research has been limited on LSD due to its prohibition as a Schedule 1 drug, much of the research carried out in the 50s and 60s show no long-term damage to the brain as a result of LSD consumption.

‘Long-term damage’ is a vague definition, however, and doesn’t address the biggest concern users have before taking LSD:

“Will it cause me to go crazy?”

The answer? Extremely, extremely unlikely.

As mentioned above, LSD can only initiate latent mental health issues, specifically schizophrenia, in individuals.

Schizophrenia, however, is rare, only affecting 1 in 100 people.

This means LSD is safe for 99% of individuals to take, as long as certain precautions are taken.

It is critically important to pay attention to set and setting when taking any psychedelic, as this will often dictate the actual journey while tripping. For more on set and setting, and the other 4’s (and how you can create an excellent environment for your first trip), check out this article on the 6 S’s.

Let’s get to the next big concern: Does LSD, or any other psychedelic, cause long-term addiction?

No. And this is what sets psychedelics apart from almost every other scheduled drug available today (including the legal ones like Adderall, Valium, Oxycontin)

LSD, and other psychedelics cause no long-term physical dependency or addiction. Although science has yet to establish the exact reasons why this is the case, it is assumed this occurs because of the manner in which psychedelics act on serotonin and dopamine receptors.

Dopamine is addictive because when a high concentration of dopamine is released, it acts on the ‘reward centers’ of the brain.

And as the ‘reward centers’ get hit with more and more dopamine, it feels really good. And this keeps addicts coming back for more and more (whether the drug is alcohol, heroin, cocaine, or a prescription drug).

Psychedelics do NOT increase the amount of dopamine available. Instead, they only act on certain dopamine receptors.

What about serotonin?

Although moderate LSD use temporarily reduces the relative levels of serotonin available, it does not have a long-term effect on serotonin levels. If abstinence is practiced, serotonin levels will return to normal within 1-2 weeks.

One long-term effect users of psychedelics should be aware of is hallucinogen persisting perception disorder (HPPD). Although this condition is extremely rare, it does happen from time to time. HPPD is characterized by a continual presence of disturbances, most often visual.

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Reader Interactions


  1. AvatarIsai Mena says

    Now I understand. I am taking a psychology class and we are learning about the brain and neurotransmitters. This made me think about the effects LSD gives to the brain. Serotonin affects hunger, sleep, arousal and mood. Which explains why when someone is on LSD, they loose appetite, sleep, increase arousal and a a happier mood.

  2. AvatarJohn Smith says

    Can you provide the source stating that LSD decreases serotonin in the brain for 1-2 weeks after?… I have never heard this before, and a quick search on a few ACTUAL studies say that it does not affect the net amount of serotonin in the brain at all (makes plenty of sense since it simply binds to the receptors).

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