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What happens to your brain on psychedelics?

March 20, 2023

Psychedelic drugs are hyped to be the new hope for treating several mental disorders. But we need to understand how they work before we can start prescribing them.

https://p.dw.com/p/4OqTC
A swirl of colors
Researchers are trying to find out what exactly happens when you take psychedelicsImage: Shotshop/imago images

The most common description for a trip on DMT, or Dimethyltryptamine, a strong psychedelic, is a "waking dream" where people interact with sentient beings, entities, perhaps even gods. Feelings of deep spirituality are common, as are those of ego death and emotional transcendence.

Suffice it to say that a 10-minute trip is incredibly dissociative from the "real" world.

What happens to your brain during such a psychedelic trip? It's unclear whether we'll ever get a satisfying answer to this question, but a new studypublished in the journal PNAS (Proceedings of the National Academy of Sciences) is bringing us closer the answer.

The researchers measured the brain activity of 20 people experiencing a 10-minute long DMT trip and found that the drug profoundly changes the way brain regions communicate with one another.

Psychedelic drugs synchronize brain activity

From the outside, it may look like a person tripping is experiencing chaos. In fact, however, studies show psychedelic drugs cause the brain to become more synchronized and interconnected.

"If you imagine an orchestra, each brain region is like a section — strings, horns etc. What happens on psychedelics is these individual sections become less synchronized within themselves, but the whole orchestra is working together better," said Christopher Timmermann, a neuroscientist at Imperial College London, UK, and a lead author on the study.

Several studies have indicated this "hyperconnectivity" of the brain during psychedelic trips, but the latest study helps to explain some of the subjective experiences of DMT.    

According to the study, brain regions involved in higher processing like creativity, imagination and emotion become hyperconnected during a DMT trip.

"We also found that alpha wave patterns in the brain are dampened in the psychedelics experience," said Timmermann. "This alpha wave is like a filter — it rises up and prevents information from our brain flooding our perceptual experience."

In other words, DMT reduces the strength of sensory inputs from the world outside while amplifying experiences generated from within the brain.

Hence the hallucinations and waking dream that many people experience on DMT.

Can ketamine and LSD cure depression?

Psychedelic drugs act through serotonin receptors

But how does DMT change brain activity? DMT, like LSD and psilocybin, tap into the serotonergic system.

It activates the serotonin 2A receptor, a small protein which sits on the surface of neurons and modulates their activity.

Where these receptors are in the brain is particularly important. It turns out they are densely expressed in regions of the cortex known to be involved in abstract and imaginative thought — the same regions that DMT hyper-connects.

However, Dietmar Schmitz, a neuroscientist at DZNE in Berlin, German, says we still don't fully understand the relationship between these serotonin receptors and brain activity changes.

"The distribution of these receptors in different brain regions or on different cell types is not 100% clear. It's really important to understand this to know how the drugs function," Schmitz told DW.

DMT may explain near-death experiences

DMT is a naturally occurring chemical that is produced in our nervous system. It's only when you take a high dose that you start to trip.

It's something of a mystery, but scientists speculate DMT is involved in shaping our normal perceptual states.

"There is emerging evidence that we have endogenous DMT in the brain. The conjecture is what function DMT has, or if we have sufficient levels of DMT to change our perception," said Timmermann.

The latest theories say that our day-to-day perception is like a controlled dream. Therefore it would make sense that DMT helps shape perception, be it in the shifting way we experience the world, or in our wackiest dreams.

Researchers have also shown that DMT trips mimic near death experiences, leading some to speculate that the long walk towards the light (or God?) could be caused by a final puff of DMT being released in the brain.

It's an intriguing thought, but as yet untested.

Clinical benefits of psychedelics

Why do we need to know about the mind of someone on drugs? Three reasons:

Firstly, to understand if they are safe.

Secondly, psychedelic research is helping us to better understand the nature of the experience and consciousness more generally.

And thirdly, guided trips using DMT, LSD, MDMA and psilocybin (the psychoactive molecule in magic mushrooms) are showing promise in treating mental disorders like depression, post-traumatic stress disorder (PTSD) and addiction.

While the effects of psychedelics on the brain are still somewhat of a mystery, we do know psychedelics have long-term effects that scientists now believe can be beneficial.

A recent US study found that activating serotonin receptors with psychedelic drugs increases plasticity in the cortex. The idea is that the plasticity is evidence that the brain is rewiring to unlearn some of the pitfalls of depressive symptoms.

According to Schmitz, the study could be a game changer.

"This paper showed that you have increased plasticity acutely after taking the drug, but also a month later. It's thought this is how you gain the antidepressant effect of psilocybin," he said.

Magic Mushrooms Psilocybin
Clinical trials show clear benefits of psilocybin, the active ingredient of magic mushrooms, in treating various mental disorders.Image: Richard Vogel/AP/picture alliance

Long-term effects of psychedelics: safe or not?

Historically, scientists believed that psychedelic drugs could have harmful long-term effects, but the latest science is shifting this narrative.

Now, study after study show positive effects after single or multiple doses of the psychedelic drug psilocybin last up to a year, maybe longer.

While Schmitz is optimistic about the therapeutic potential of psychedelics, he cautions that we need to know more about how they work.

"There's a lot of hype around psychedelics, but they need to be investigated seriously. They have clear benefits for some people, but it's not that they will heal everyone's depression," said Schmitz.

In particular we need to know more about potential negative effects on the brain.

Scientists are of course working on this. Questions about safety risks and side effects, how psychedelics affect young people, or people with existing mental disorders, are under rigorous investigation in clinical trials.

The outcome of these trials will determine the future of psychedelic therapies.

Therapy without the trip?

One intriguing idea that gets around the safety argument is that you could deliver a drug that has all the beneficial properties to treat depression, but it doesn't cause a trip.

Scientists in the US are working on an LSD-like drug which does exactly this. The researchers claim it might be a safer way to treat depression.

However, experts argue the psychedelic experience itself is essential for the healing effects.

"There's a scientific argument that the quality of that experience leads to positive changes in mental health, so incorporating it into the therapy is important for mental health treatment," said Timmermann.

In the end it's a scientific conundrum — what's the safest and most effective way we can use psychedelics for clinical treatments?

Edited by: Carla Bleiker

DW journalist Fred Schwaller wears a white T-shirt and jeans.
Fred Schwaller Science writer fascinated by the brain and the mind, and how science influences society@schwallerfred