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Psychedelic drugs boost some of the crosstalk between brain regions.Credit: K H Fung/Science Photo Library

Different psychedelic drugs have a strikingly similar effect on networks in the brain, finds the most comprehensive analysis so far of the mind-altering substances.

The work, published in Nature Medicine on 6 April1, identified a ‘signature’ pattern of brain activity associated with taking five psychedelics, including psilocybin, LSD and ayahuasca. It combines data from 11 brain-imaging studies, which in turn include more than 500 brain scans of 267 people.

“The most surprising finding is that, 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,” says study co-author Danilo Bzdok, a neuroscientist and AI researcher at McGill University in Montreal, Canada. “This puts a question mark on how we’re even categorizing them.”

The analysis is “the largest study of its kind so far”, says Shan Siddiqi, a psychiatric neuroscientist at Harvard Medical School in Boston, Massachusetts. Most neuroimaging studies of psychedelic drugs have recruited a limited number of participants, he says. “This is a first step towards correcting that limitation.”

Dozens of clinical trials have supported the idea that psychedelics could help to treat conditions such as depression, anxiety and addiction. Understanding how these substances affect the brain “will inform future drug design for this potentially very important category of drugs for the future of mental health”, says Bzdok.

Mysterious trips

Psychedelics temporarily alter people’s perception and cognition, but the neural mechanisms that underlie their effects have remained unclear.

Studies to explore what happens inside the brain during a psychedelic trip have also been small and sometimes produce conflicting results. The scientific evidence is “very fragmented, very nascent with a lot of potential, but not very mature”, says Bzdok.

To address these limitations, he and his colleagues developed a way of combining many different scans and analysing how activities in various parts of the brain fluctuate together over time. They applied their approach to brain-imaging data sets from the United Kingdom, Switzerland, the Netherlands, the United States and Brazil, which examined the effects of psilocybin, LSD, mescaline, DMT (N,N-dimethyltryptamine) as well as the DMT-containing brew, ayahuasca.

“The prevailing theory in psychedelic science is this notion of, you take a psychedelic like psilocybin and it will dissolve or disintegrate your brain networks,” says Petros Petridis, a psychiatrist at New York University who studies psychedelics.

But the analysis by Bzdok and his colleagues found that the drugs actually boosted the crosstalk between brain regions. For participants who took the drugs, brain networks that are typically involved in advanced cognitive processing were “much more connected among each other than in a sober individual”, explains Bzdok.

And these neural circuits were also more strongly connected to brain networks that process vision and sound, and those that coordinate motor control, in participants who took the drugs. There were also changes in brain activity between subcortical brain regions that are involved in perception, motivation and our sense of reward.

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doi: https://doi.org/10.1038/d41586-026-01053-2

References

- Girn, M. et al. Nature Med. https://doi.org/10.1038/s41591-026-04287-9 (2026).

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Your brain on drugs: different psychedelics work in surprisingly similar ways