Apart from the wide-eyed bike ride home from the lab, his neighbour turning into a witch, the threatening behaviour of his furniture and the futile battle to save his ego from collapse, Dr Albert Hofmann appeared to enjoy his first trip on LSD.



Now, 75 years after the Swiss chemist witnessed the full effects of his psychedelic invention, scientists have discovered fresh details of how the drug affects the brain. Scans of healthy volunteers show that less than half the dose that left Hofmann cowering on his sofa makes a person’s sense of self disintegrate.



Researchers at the University of Zurich gave willing participants 100 micrograms of LSD – compared with the 250 micrograms Hofmann took on what is now known as “bicycle day” in 1943 – and found that in social interactions with computer avatars, the drug dampened down brain activity that helps people distinguish themselves from others.



“Our interpretation is that LSD reduces your sense of integrated self,” said Katrin Preller, a psychologist who worked on the study. “In this particular case, the drug blurs the boundary between what is you and what is another person.”



The dissolution of the ego, or self, that destroys the normally concrete sense of where one person ends and another begins, underpins the experience that some LSD users report of feeling at one with the cosmos.



Preller and her colleagues studied LSD, or lysergic acid diethylamide, or plain “acid”, to learn how the brain creates a sense of self. By shedding light on the mystery, they hope to find new treatments for symptoms of psychiatric disorders such as depression and schizophrenia, where the sense of self can become heavily distorted.



“We don’t currently have any medications that work to improve the social deficits in psychiatric disorders,” she said, “and one of the reasons for that is we have no real understanding of how social interaction works in the brain.”



The scientists recruited 24 people for the study. While some were given LSD, others received a placebo, while others still had LSD plus ketanserin, a drug that blocks the receptor in the brain which LSD works on. Those who took only LSD reported various experiences, such as disembodiment, a heightened sense of unity and visual hallucinations.

For the study, the volunteers lay in a brain scanner and took part in simulated social interactions. Specifically, they had to make eye contact with a computer avatar and then either lead or follow its gaze to an object on the screen. Now and then, the avatar looked the wrong way. On other occasions, when it was the avatar’s turn to lead the gaze, the patient was instructed to look in the opposite direction.



The scans revealed that parts of the brain involved in creating a sense of self became more active when people took the lead in the computer interactions, and when they looked the same way as the avatar. But when they took LSD, this difference in brain activity was far less obvious, according to a report in the Journal of Neuroscience. As expected, volunteers who took ketanserin felt no effects from the psychedelic. “It gets rid of this blurring between self and other, and the basic deficits in social interaction go away,” Preller said.

The work bolsters research that suggests drugs that target the same brain networks as LSD might have a role in helping patients with a variety of mental disorders.

Anil Seth, a cognitive neuroscientist at Sussex University who has worked on the mind-altering effects of the drug, praised the study, adding that it was “challenging” to have people on LSD perform tasks while lying in a brain scanner. “This is an excellent example of how combining multiple methods from pharmacology, brain imaging and cognitive science can bridge the distance all the way from neurotransmitter systems to changes in the ‘social self’,” he said.



“Since changes of this sort are characteristic of many psychiatric conditions, this study opens new opportunities for interventional treatments of conditions like depression and schizophrenia,” he added.



Robin Carhart-Harris, head of psychedelic research at Imperial College London, said the paper was an “important contribution to our understanding of how psychedelic compounds like LSD work in the human brain”.



“The result appears to back up the view that an important brain network linked to our sense of self or ego is particularly affected by psychedelics,” he said, “which may explain why they can alter consciousness so profoundly.”