How Do Different Psychedelics Affect the Brain? Scientists Analyzed More Than 500 Neural Scans to Find Out

A new study suggests that four psychoactive compounds work in surprisingly similar ways, and that they break down the separation between how we think internally and how we perceive the outside world

Sara Hashemi | Daily Correspondent

April 15, 2026

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Mind-altering psychedelics continue to show promising research results as potential therapeutics for certain mental health conditions, such as post-traumatic stress disorder and depression. But scientists still don’t know exactly how these substances affect the brain.

Now, researchers have identified a “signature” pattern of neural activity evoked by different psychedelics—including LSD and psilocybin—after analyzing more than 500 brain scans from 267 participants across the globe. The work, published April 6 in the journal Nature Medicine, represents the largest, most comprehensive study of its kind and hints that the hallucinogenic compounds boost activity between brain networks that work across many regions, such as those involved in thinking, and more isolated ones, like those involved in vision and touch.

“Usually, the brain’s perception of the external world is very distinct from our memory and abstract thinking,” Manesh Girn, a study co-author and neuroscientist at the University of California, San Francisco, tells National Geographic’s Meryl Davids Landau. “This is suggesting the psychedelics might close that gap between how we think and how we perceive—between the internal and external.”

Many research groups have individually examined what psychedelics do to the brain by scanning people in MRI machines while they aren’t focused on a task, or at resting state. But the studies have involved small numbers of participants, and they’ve turned up inconsistent results.

That’s partially because psychedelic research is in such an early state, says Danilo Bzdok, a study co-author and neuroscientist at McGill University in Canada, to the New York Times’ Andrew Jacobs. But another reason is that scientists in the field use diverse methods to measure and interpret brain activity.

To remedy this, Bzdok, Girn and their colleagues spent five years compiling 11 resting-state fMRI datasets from five countries spanning three continents. These involved research on four different psychedelics: psilocybin, LSD, mescaline found in the peyote cactus and DMT, including that in the traditional brew ayahuasca. Processing all the data in the same way revealed the psychoactive compounds’ similar effects.  

“Despite the discrepancies in the pharmacology and the pharmaco-physiological properties of these drugs, there is a common denominator of how they affect the human brain,” Bzdok tells Nature’s Miryam Naddaf. The finding, which he calls surprising, “puts a question mark on how we’re even categorizing them.”

What’s more, the work challenges previous research that suggested psychedelics disintegrate the brain’s networks. The drugs seem to strengthen certain connections between brain regions, the team found. For instance, in participants who took the drugs, areas implicated in advanced cognitive processing were “much more connected among each other than in a sober individual,” Bzdok tells Nature.

The study is a “tour de force,” Amy Kuceyeski, a neuroscientist at Weill Cornell Medicine who was not involved in the research, tells the Times. Still, she would have appreciated seeing how a person’s age and sex might impact the substances’ effects.

Overall, the increased integration of information across brain regions “may be how [psychedelic therapy] can break down rigid cognitive patterns and increase flexibility of thought, which has been proposed as one explanation of how they can produce healing in patients with depression and addictive disorders,” says Christopher Pittenger, a psychiatrist and director of Yale University’s Program for Psychedelic Science, who was not involved in the research, to National Geographic.

As the field of psychedelic research advances, the team hopes that scientists will map the full range of experiences people have reported while on the drugs. For example, while the new study involved brain scans from people minutes into their mind-altering events, a psychedelic trip can last for hours.  

“There’s a huge variety one can have over the time—whether that’s having insane visual experiences or ‘ego death,’ or remembering memories or processing emotions,” Girn tells National Geographic. Future studies could “characterize how those might look differently in the brain and how that could relate to outcomes in therapy.”

Sara Hashemi | Read More

Sara Hashemi is a science writer and fact-checker currently based in New York City. Her work has appeared in Sierra, The Body, Maisonneuve magazine and more.