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LSD Makes Your Brain More ‘Flexible,’ Less Anxious

Breakthrough research shows how psychedelic drugs like LSD and psilocybin expand the brain.

Psychedelic drugs like LSD and magic mushrooms seem to have gone the way of other hippie trends, like flower power, free love, and tie-dye. For a small group of scientists, however, psychedelics hold the promise not of sex, drugs, and rock ’n’ roll, but of understanding some of the inner workings of the human brain. The renaissance of LSD, psilocybin, and MDMA (aka Ecstasy) in neuropsychiatric research is providing scientists with new insights into how our brains construct reality.

Last week, a pair of new studies revealed some of the first images of neural activity in people who had taken LSD. A far cry from the “This is your brain on drugs” ads of the 1980s, this new research shows that your brain on LSD actually involves a breakdown of the factors that normally keep neural circuits separate. The result? That stereotypical feeling of feeling “at one” with the world and part of something larger than yourself.

“These studies are a real milestone. We’re at the beginning of a new era in psychedelic research. It’s becoming more mainstream,” said Robin Carhart-Wright, a neuroscientist at Imperial College London and co-leader of both of these studies.

Swiss chemist Albert Hofmann first synthesized Lysergic acid diethylamide in 1930. By the 1950s and ’60s, psychologists and neuroscientists were experimenting with the drug’s therapeutic potential. At the time, Freudian psychoanalysis was at its peak. Freud had said that dreams were the key to accessing the brain’s subconscious, and psychologists believed that taking LSD as part of psychotherapy could provide a shortcut, allowing patients to make larger breakthroughs in shorter time periods.

For about 10 years, LSD research was de rigueur among forward-thinking psychologists. But as people began to take LSD recreationally in the 1960s, and it became associated with anti-establishment and counter-cultural movements, the government ultimately made the drug illegal.

This effectively brought a halt to research on LSD, psilocybin, and other psychedelic drugs. In the past decade, however, neuroscientists have renewed their interest in these compounds, not just for their potential therapeutic uses, but also for what they can tell us about the inner workings of the brain. It’s this latter option that first drew Carhart-Wright to psychedelic research.

“There are many different ways of accessing the unconscious mind, and drugs are one of those possibilities,” he said. “There’s a lot more to the mind than normal, waking consciousness.”

Starting any type of major research project is a complex undertaking, and it’s even more so when you’re working with a controlled substance that can occasionally have unpredictable effects on users. But Carhart-Wright believed in the possibilities of psychedelic research, and began collaborating closely with David Nutt, also at Imperial College London, and one of the world’s leading experts in illicit drugs. They started with psilocybin and MDMA, because they were easier to get ahold of and research.

But Carhart-Wright remained interested in LSD and finally got his chance to use functional magnetic resonance imaging (fMRI) to study what happened in the brain of people while they were tripping on LSD. He obtained funding for his project via crowdsourcing and via the Beckley Foundation, which funds research on the potential beneficial usage of illicit drugs.

Because LSD was known to give people bad trips, and because participants would have to lie down and remain still in an fMRI scanner for an extended period, the researchers knew they would have to select participants carefully. Carhart-Wright ensured that a nurse and psychiatrist were on hand during every experiment, for the entire 8-10 hours it took for the drugs to wear off. They ultimately selected 20 healthy adults, all of whom had tried LSD before, and invited them into the lab on two separate occasions.

On one occasion, they were injected with a placebo. On another, they received 75 micrograms of LSD. In both cases, their brain activity was scanned while resting comfortably in the fMRI machine. Two other complementary neuroimaging techniques were also used, and they published their results in the journal PNAS.

Carhart-Wright and colleagues found that LSD intensified activity in the visual cortex, and that the drug also increased the connections between this region to other parts of the brain. These changes, they believe, are correlated with LSD’s ability to cause visual hallucinations. The researchers observed other changes, too. It simultaneously decreased connections between the parahippocampus and retrosplenial cortex (RSC), brain areas that are involved in memory and navigation. These changes, the scientists believe, are linked to feelings of being part of a larger whole that frequently accompany LSD use.

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Our brain normally separates our body from the rest of the world, which is an important step in being able to interact with the environment around us. “LSD breaks down those barriers,” Carhart-Wright said. “It creates stroking and unusual brain changes, creating a more flexible, labile brain,” which is an important factor for people in psychotherapy who are usually trying to enact some form of behavioral change.

In a related study in Current Biology, published two days after the PNAS paper, Carhart-Wright and neuroscientist and physicist Enzo Tagliazucchi, of the University of Kiel in Germany, focused more on this phenomenon, known as ego depletion. Analysis of fMRI images of the brain on LSD reveals that the drug broadly increases the functional connectivity across the entire brain. Increased cross-talk between different brain regions opens the mind to new experiences and seems to integrate the self with the rest of the world.

Other research on psychedelic drugs given to dying cancer patients struggling with anxiety over their impending deaths has shown that this type of experience can be very helpful in relieving the sense of over-arching doom. Building on evidence from more than half a century ago, other studies are showing that these drugs may be helpful in relieving anxiety more broadly. For neuroscientists like Tagliazucchi, however, these drugs provide a novel way to simply understand how the brain goes about its everyday duties.

“We think that what we experience normally is reality, but the truth is our brains are just constructing reality for us,” Tagliazucchi said.