Acid test: scientists show how LSD opens doors of perception

By Ian Sample

When Aldous Huxley emerged from a mescaline trip that veered from an obsession with the folds in his trousers to wonder at the “miraculous” tubularity of the bamboo legs on his garden chairs, he offered an opinion on how the drug worked.

Writing in The Doors of Perception, his 1954 book that took its name from a William Blake poem, Huxley declared that the psychedelic “lowers the efficiency of the brain as an instrument for focusing the mind on the problems of life”.

Even for Huxley, the assessment now seems remarkably prescient. In new research, scientists have found evidence that LSD, another psychedelic, lowers the barriers that constrain people’s thoughts. In doing so, it frees the mind to wander more easily and experience the world anew.

“Normally, our thoughts and incoming information are filtered by our prior experience,” said Parker Singleton, a PhD candidate at Cornell University in New York. “But if you take that filtering and suppression away, you are looking at the world with new eyes. You get a totally new perspective.”

Singleton and his colleagues set out to test the so-called Rebus model of psychedelics. Standing for “relaxed beliefs under psychedelics”, it frames the brain as a prediction engine. Under the model, the brain takes thoughts and information from the senses and shapes them according to its understanding of the world. This makes the brain highly efficient: armed with prior beliefs, the noise and uncertainty of perception and thought are swiftly hammered into coherent reality.

But the brain works differently on psychedelics. According to Rebus, substances such as LSD weaken the influence of prior beliefs that the brain uses to make sense of the world. In one sense, the drugs rewind the brain’s clock to a time before it learned that walls tend not to move and furniture is rarely threatening.

“You can imagine you might experience altered perceptions,” said Amy Kuceyeski, a senior author on the study at Cornell. “If your prior belief is that walls don’t move and your prior belief melts, then that wall may appear to move.”

The scientists analysed fMRI brain scans of people on placebo or LSD. These revealed four distinct states, or patterns of activity, that the brain switched between when the volunteers were resting in the scanner. Two of the brain states were largely driven by sensory parts of the brain, while the other two involved the kind of top-down processing the brain performs to make sense of the world. On LSD, the brain spent less time on higher-level processing and more on the sensory-driven activities.

By comparing scans of the brain on LSD versus placebo, the researchers found that the drug reduced the amount of energy the brain needed to switch from one brain state another. Dr Kuceyeski likens it to flattening the landscape over which the brain can roam. Normally, the brain’s activity is constrained by the mountains and valleys of our prior beliefs, but on LSD these obstacles are flattened out. “It allows us to move more freely and have more dynamic brain activity,” she said.

Writing in a preprint, which has yet to be peer-reviewed, the researchers go on to show how the distribution of a particular receptor called 5-HT2a, the primary target for LSD, enables the drug to have such a profound levelling effect.

David Nutt, professor of neuropsychopharmacology at Imperial College London, who was not involved in the research, said that “flattening the landscape” allowed parts of the brain to talk to each other for the first time since early childhood.

“The whole process of child development and education is to take your brain, which is extremely malleable, and force it to be like everyone else’s brain. Under psychedelics, you go back to a state where bits of the brain that haven’t spoken since you were a baby can cross-talk. And it’s that increased connectivity that allows people to get new insights into old problems,” he said.

The ability of LSD to free up brain activity may explain why psychedelics can help people with depression, anxiety and other mental health disorders such as post-traumatic stress disorder.

“In depression, people get locked into a way of thinking that is repetitive and ruminative. It’s like tramline thinking,” said Nutt. “Psychedelics disrupt those kinds of processes so people can escape from it.”