Study unpacks how LSD lowers brain’s barriers

In 1957, when the British psychiatrist Humprhey Osmond was looking to coin a word for the mind-bending effects of LSD, he wrote a letter to his friend Aldous Huxley. The "Brave New World" author — who had also written a book called "The Doors of Perception" detailing his experiences with the hallucinogenic drug mescaline — suggested to Osmond the word "phanerothyme" — taken from the Greek for "to show" and "spirit." Osmond didn’t think this was at all pleasant-sounding, so he made a counter proposal, built from the Greek words for "soul" and "manifest" — psychedelic.

Many summers of love later and the experiences had with the drug, along with the word that describes them, have become firmly woven into our culture. A psychedelic experience, whether it's induced by a mind-altering drug or not, is, at the very least, a disorienting one. And in moving a person away from preconceived notions and forcing them to confront reality anew, it manifests the buried inner workings of one’s mind, or "soul" — exactly as Osmond felt it did. 

But it’s only recently that scientists have begun to grapple with what exactly LSD does to the brain, and they've found evidence that it really does blow open your mind. According to new research, psychedelic drugs put the brain into a state where it can flow more freely, unconstrained by prior beliefs of how the world is supposed to work. The findings also have implications for treating anxiety and depression, the researchers said.

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"When you’re a child your brain is very malleable, you don’t have all of these models for your whole life yet, you’re more able to continuously update your beliefs." Parker Singleton, a doctoral candidate at Cornell University in New York, told Live Science. "At some point those models harden, and they become more difficult to shape. Under psychedelics we open up a new window to do that."

This, says Singleton, is the "relaxed brain under psychedelics" or "Rebus" model that his team set out to examine. The brain, according to the hypothesis, is like an engine that generates predictions about the world based on prior experiences. As these experiences accumulate, the engine becomes more refined and efficient — increasingly capable of cutting through extraneous noise — but at the cost of becoming more rigid and more likely to discard harder-to-classify experiences. Psychedelic drugs, the hypothesis suggests, unwind the influence one’s prior beliefs have on the brain, allowing thoughts to flow more freely, unimpeded by past assumptions.

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"As just one example, what our brain does on a daily basis is predict faces. It’s very easy to see a face in a cloud or on any object," said Singleton, referring to the phenomenon of "face pareidolia" that led some to spot a face on the surface of Mars from a photo taken by NASA’s 1976 Viking 1 orbiter.

Parallels to this can also be drawn to the Tufts University neuroscientist Erik Hoel’s "noisy brain hypothesis," which attempts to explain why we dream. According to Hoel, the brain goes about constructing patterns from observations of the world in much the same way a prediction-generating AI does. And, much like an AI, the brain can become "overfitted" — too accustomed to the repetitive dataset a person’s routines provide and less capable of adapting to new situations. Dreams exist to inject some much needed noise to loosen up our systems — offering a phantasmagoric jolt to prepare them for unexpected scenarios.  

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To test the Rebus model, Singleton’s team analyzed magnetic resonance imaging (fMRI) brain scans, taken from a 2016 Imperial College London study, of 20 healthy volunteers either on a placebo or on LSD. They saw that the volunteers’ brains switched between four distinct states, or activity patterns, while they rested inside the scanner — two of the states primarily involved the sensory parts of the brain, and the other two were more connected to the top-down, analytical brain regions responsible for generating accurate pictures of the world. The researchers noticed that those who were tripping  on LSD, however, were spending far longer in the sensory brain states than the analytical ones. 

Further comparison between the LSD brains and the placebo ones also revealed an even more fascinating phenomenon: The LSD brains required far less energy to move from one brain state to another.

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"If you think of our neural connections as like a series of roads and highways, LSD doesn’t change the roadways, but it does lower the energy you need to get from one to the other," Singleton said. "It flattens the energy landscape between different parts of the brain, bringing them closer together." 

LSD acts on the brain by binding to a serotonin receptor called 5-HT2a, and the team also found through spatial analysis that this receptor is distributed throughout the brain so as to significantly boost the energy-leveling effect.

This flattening enables brain regions that wouldn’t usually talk with one another to suddenly enter into garrulous conversation. This may be the cause of the childlike "freshness" of perspective that users of the drug often report, according to Singleton. As familiar resemblances melt away and the boundaries between objects become blurred, users can find themselves fascinated by the foreign appearance of once unremarkable items. In "The Doors of Perception," Huxley describes brief obsessions with the folds of his trousers; the zebra pattern made by sunlight shining through the slats of a garden chair; and the self-satisfied appearance of a friend's car, which caused him to erupt into laughter. 

This profound shift in brain activity could explain why psychiatrists have begun to consider integrating psychedelics into treatments for mental health disorders such as PTSD, anxiety and depression, according to recent studies. 

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"Our hypothesis is that in a diseased state, your brain is going to have higher energy hills and lower energy valleys. More so than a placebo, different parts of their brain can’t talk to each other," Singleton said. "That’s why someone stuck in a negative pattern of thought could be having a hard time — in spite of new evidence they’re not able to see that there are reasons to be happy. Psychedelic therapy could flatten out that energy landscape again and allow more information to come in. It could allow depressed or anxious people to update their models of the world."

Next, the team plans to use LSD to further map out different states of consciousness. This will enable them to further explore the therapeutic relevance of the drug.

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"I’m not a clinician, but if it continues to be safe and effective I could imagine it becoming a very useful psychoanalytical tool," Singleton said. "You don’t have to have treatment-resistant depression to benefit from it, any therapy process could be helped by it."

The researchers published their findings May 17 on the preprint server bioRxiv, so the study has yet to be peer-reviewed.

Originally published on Live Science