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The psychedelic compound found in magic mushrooms not only gives people a day trip – it can influence the brain for weeks, researchers have found.

Experts say the study helps explain why taking psilocybin – the active ingredient in the drug – can result in a distorted sense of space, time and self during a trip, as well as shed light on the mechanism by which it can help in the treatment of severe depression.

Dr Joshua Siegel, a co-author of the work from Washington University School of Medicine in St Louis, said the research may also bring benefits to companies testing novel psychedelics and similar, but non-hallucinogenic, drugs.

“It could help to determine if a novel drug is hitting the right targets and to decide what is the optimal dose,” he said.

Writing in the journal Nature, Siegel and a team of colleagues report how they carried out a randomised control trial with seven healthy participants who agreed to take psilocybin in the name of science.

“It was also a requirement that they had taken a psychedelic at some point in their life, partly because they were taking a high dose, equivalent to 5g of magic mushrooms, and they were getting into a big, loud, banging, claustrophobic magnet [while] on psilocybin,” said Siegel, adding the team needed to be sure participants would be able to tolerate the situation.

“So we wanted to try to make sure that we knew that they would be able to tolerate that.”

The participants were randomly assigned either a 25mg dose of psilocybin, or a 40mg of methylphenidate – the generic form of Ritalin – but were kept in the dark about which they had been given. One to two weeks later the participants were given the drug they did not initially receive.

The participants underwent MRI scans before, during, between and after being given each drug, while after six to 12 months four of the participants returned to receive another dose of psilocybin and scans. Participants made, on average, 18 MRI visits each.

The results reveal taking psilocybin – but not methylphenidate – was associated with a loss of synchrony in what is known as the default mode network. This is an interconnected group of brain regions that is active when the mind is wandering and the brain isn’t working on a particular task. Crucially, says Siegel, this network is involved in creating a sense of self, as well as showing links to the perception of space and time.

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Design replicates brain activity

“The interpretation is that [that disruption is] what creates this very out of the ordinary experience [when taking psilocybin],” said Siegel.

While participants’ brain scans largely returned to normal the day after taking psilocybin, Siegel noted a reduction in communication between the default mode network and the anterior hippocampus – a part of the brain critical for memory and perceptions of space and time – lasted for three weeks after the dose.

Siegel said the finding may help explain reports of an increase in flexibility in how people view themselves and their relationship to their environment after taking psilocybin. This plasticity is thought to underpin psychedelic-based interventions for conditions such as treatment-resistant depression by making the brain more open to therapy.

Siegel added while the research process was demanding, there seemed to be plenty of volunteers for studies into psychedelics. “We didn’t have trouble finding participants,” he said.



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