2269. Brain on LSD Revealed: First Scans Show How the Drug Affects the Brain

By Science Daily, April 11, 2016

Researchers from Imperial College London, working with the Beckley Foundation, have for the first time visualized the effects of LSD on the human brain.

In a series of experiments, scientists have gained a glimpse into how the psychedelic compound affects brain activity. The team administered LSD (Lysergic acid diethylamide) to 20 healthy volunteers in a specialist research centre and used various leading-edge and complementary brain scanning techniques to visualize how LSD alters the way the brain works.

The findings, published in Proceedings of the National Academy of Sciences (PNAS), reveal what happens in the brain when people experience the complex visual hallucinations that are often associated with LSD state. They also shed light on the brain changes that underlie the profound altered state of consciousness the drug can produce.

A major finding of the research is the discovery of what happens in the brain when people experience complex dreamlike hallucinations under LSD. Under normal conditions, information from our eyes is processed in a part of the brain at the back of the head called the visual cortex. However, when the volunteers took LSD, many additional brain areas -- not just the visual cortex -- contributed to visual processing.

Dr Robin Carhart-Harris, from the Department of Medicine at Imperial, who led the research, explained: "We observed brain changes under LSD that suggested our volunteers were 'seeing with their eyes shut' -- albeit they were seeing things from their imagination rather than from the outside world. We saw that many more areas of the brain than normal were contributing to visual processing under LSD -- even though the volunteers' eyes were closed. Furthermore, the size of this effect correlated with volunteers' ratings of complex, dreamlike visions. “

The study also revealed what happens in the brain when people report a fundamental change in the quality of their consciousness under LSD.

Dr Carhart-Harris explained: "Normally our brain consists of independent networks that perform separate specialised functions, such as vision, movement and hearing -- as well as more complex things like attention. However, under LSD the separateness of these networks breaks down and instead you see a more integrated or unified brain.

"Our results suggest that this effect underlies the profound altered state of consciousness that people often describe during an LSD experience. It is also related to what people sometimes call 'ego-dissolution', which means the normal sense of self is broken down and replaced by a sense of reconnection with themselves, others and the natural world. This experience is sometimes framed in a religious or spiritual way -- and seems to be associated with improvements in well-being after the drug's effects have subsided.”

Dr Carhart-Harris added: "Our brains become more constrained and compartmentalized as we develop from infancy into adulthood, and we may become more focused and rigid in our thinking as we mature. In many ways, the brain in the LSD state resembles the state our brains were in when we were infants: free and unconstrained. This also makes sense when we consider the hyper-emotional and imaginative nature of an infant's mind.”

In addition to these findings, research from the same group, part of the Beckley/Imperial Research Programme, revealed that listening to music while taking LSD triggered interesting changes in brain signalling that were associated with eyes-closed visions.

In a study published in the journal European Neuropsychopharmacology, the researchers found altered visual cortex activity under the drug, and that the combination of LSD and music caused this region to receive more information from an area of the brain called the parahippocampus. The parahippocampus is involved in mental imagery and personal memory, and the more it communicated with the visual cortex, the more people reported experiencing complex visions, such as seeing scenes from their lives.

PhD student Mendel Kaelen from the Department of Medicine at Imperial, who was lead author of the music paper, said: "This is the first time we have witnessed the interaction of a psychedelic compound and music with the brain's biology.

The Beckley/Imperial Research Programme hope these collective findings may pave the way for these compounds being one day used to treat psychiatric disorders. They could be particularly useful in conditions where negative thought patterns have become entrenched, say the scientists, such as in depression or addiction.

Mendel Kaelen added: "A major focus for future research is how we can use the knowledge gained from our current research to develop more effective therapeutic approaches for treatments such as depression; for example, music-listening and LSD may be a powerful therapeutic combination if provided in the right way.”

Professor David Nutt, the senior researcher on the study and Edmond J Safra Chair in Neuropsychopharmacology at Imperial, said: "Scientists have waited 50 years for this moment -- the revealing of how LSD alters our brain biology. For the first time we can really see what's happening in the brain during the psychedelic state, and can better understand why LSD had such a profound impact on self-awareness in users and on music and art. This could have great implications for psychiatry, and helping patients overcome conditions such as depression.”

Amanda Feilding, Director of the Beckley Foundation, said: "We are finally unveiling the brain mechanisms underlying the potential of LSD, not only to heal, but also to deepen our understanding of consciousness itself.”

The research involved 20 healthy volunteers -- each of whom received both LSD and placebo -- and all of whom were deemed psychologically and physically healthy. All the volunteers had previously taken some type of psychedelic drug. During carefully controlled and supervised experiments in a specialist research centre, each volunteer received an injection of either 75 micrograms of LSD, or placebo. Their brains were then scanned using various techniques including fMRI and magnetoencephalography (MEG). These enabled the researchers to study activity within the whole of the brain by monitoring blood flow and electrical activity.

Journal References:

1 Robin L. Carhart-Harris, Suresh Muthukumaraswamy, Leor Roseman, Mendel Kaelen, Wouter Droog, Kevin Murphy, Enzo Tagliazucchi, Eduardo E. Schenberg, Timothy Nest, Csaba Orban, Robert Leech, Luke T. Williams, Tim M. Williams, Mark Bolstridge, Ben Sessa, John McGonigle, Martin I. Sereno, David Nichols, Peter J. Hellyer, Peter Hobden, John Evans, Krish D. Singh, Richard G. Wise, H. Valerie Curran, Amanda Feilding, and David J. Nutt. Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences (PNAS), April 2016 DOI: 10.1073/pnas.1518377113

2 M. Kaelen, L. Roseman, A. Lebedev, J. Kahan, A. Santos-Ribeiro, C. Orban, R. Lorenz, D. Nutt, R. Carhart-Harris. P.3.039 Effects of LSD and music on brain activity. European Neuropsychopharmacology, 2016; 26: S80 DOI: 10.1016/S0924-977X(16)70088-5

2257. Researchers Study the Benefits of Psychedelics

By Daniel Miller, The Washington Post, April 1, 2016

In 1970, Congress dropped psychedelics into the war on drugs. After a decade of Timothy Leary, “The Electric Kool-Aid Acid Test” and news reports of gruesome murders, the federal government declared that the drugs had no medical use — and high potential for abuse. The chairman of New Jersey’s Narcotic Drug Study Commission called LSD “the greatest threat facing the country today . . . more dangerous than the Vietnam War.”

But over the past decade, some scientists have begun to challenge that conclusion. Far from being harmful, they found, hallucinogens can help sick people: They helped alcoholics drink less; terminal patients eased more gently into death. And it’s not just the infirm who are helped by the drugs. Psychedelics can make the healthy healthier, too.

On this subject, only a handful of peer-reviewed studies have been conducted; sample sizes are tiny. There’s still a great deal researchers don’t know. But early results suggest that, when used by people without a family history or risk of psychological problems, psychedelics can make us kinder, calmer and better at our jobs. They can help us solve problems more creatively and make us more open-minded and generous. Some experiments even suggest that a single dose can change our personalities forever.

Is it possible that a drug labeled as one of the most destructive and dangerous could make everyone’s lives better?

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Americans have had a complicated history with psychedelics like LSD, magic mushrooms and peyote. In the 1950s, researchers began to investigate whether psychedelics could treat mental-health disorders and addiction. Between 1953 and 1973, the federal government funded 116 studies on the subject, affecting thousands of people.

At the same time, large numbers of Americans started using these drugs recreationally. 

As many as 2 million had dropped acid by 1970. Stories about “bad trips” and psychotic breaks emerged in the press. In one widely publicized incident, a 5-year-old accidentally took her uncle’s drug; people got scared. Meanwhile, soldiers were returning from Vietnam addicted to heroin; the country felt like it was locked in battle with illegal drug use. By 1968, President Richard Nixon had declared drugs “public enemy number one.” Congress banned all psychedelic use in 1970, which made research nearly impossible.

Then, in the early 2000s, a handful of scientists began looking into psychedelics as a way to relieve anxiety and addiction. (They were drawn to the drugs after reviewing the work of researchers from the 1950s and ’60s.) These experiments were successful. In one study, cancer patients were given psilocybin, a component of psychedelic mushrooms. Each patient was given one dose and then allowed to trip in a hospital room designed to look like a living room. Two medical professionals stayed close by.

Afterward, almost all of the participants experienced a significant reduction in anxiety and depression. Scientists checked in with the patients six months later; all reported that they still felt calmer and happier. Volunteer Gail Thomas told me that the treatment helped her overcome a deep sense of loneliness. “The main message from the trip was that we’re all connected,” she said. “We’re not alone.”

“The fact that a drug given once can have such an effect for so long is an unprecedented finding,” NYU psychiatrist Stephen Ross told the New Yorker. “We have never had anything like it in the psychiatric field.”

Other researchers have tested the drug as a treatment for depression, addiction and other mental problems such as obsessive-compulsive disorder. Remarkably, in each small trial, scientists saw incredible results.

In a 2014 smoking-cessation study published in the Journal of Psychopharmacology, 15 participants were given three doses of psilocybin under careful supervision by doctors. The participants were all heavy nicotine users, consuming about a pack a day for an average of 31 years. Six months later, 80 percent were cigarette-free — most smoking-cessation efforts are about 35 percent effective. In a 2015 alcoholism study, also peer-reviewed and published in Psychopharmacology, many of the 10 participants saw a significant decrease in drinking for at least nine months after one or two psilocybin experiences. In both studies, the psilocybin doses were coupled with therapy.

Here’s why scientists think it works: When someone takes a psychedelic, there is a decrease in blood flow and electrical activity in the brain’s “default mode network,” a group of brain structures found in the frontal and pre-frontal cortex. The default mode network is primarily responsible for our ego or sense of self; it “lights up” when we daydream or self-reflect.

When we trip, our default mode network slows down. With the ego out of commission, the boundaries between self and world, subject and object dissolve. These processes may be related to something called the “primary mystical experience,” a phenomena highly correlated with therapeutic outcomes. As Matthew Johnson, a principal investigator in Johns Hopkins’s psilocybin studies, explains, these experiences include a “transcendence of time and space,” a sense of unity and sacredness and a deeply felt positive mood.

Robin Carhart-Harris, a neuroscientist with Imperial College London, notes that the default mode network is responsible for a lot of our rigid, habitual thinking and obsessions. Psychedelics help relax the part of the brain that leads us to obsess, which makes us calmer. And they can help “loosen if not break” the entrenched physical circuits responsible for addictive behavior.

There’s also an increase in activity between different parts of the brain that don’t normally communicate — what scientists call “cross-talk.” That may be why we hallucinate while on psychedelics; the brain’s visual-processing centers are interacting in strange ways with the parts of the brain that control our beliefs and emotions.

 * * *

Of course, it’s not just the mentally ill who need to feel less isolated and obsessive, more fulfilled and creative. Research has shown that healthy people also benefit from the brain shift that psychedelics provide. Taking the drug even one time can fundamentally reshape our lives, making us happier and kinder, more productive at work and more open-minded. These findings are one of the reasons I became a psychedelics advocate.

In one study (admittedly, one that didn’t follow today’s rigorous research parameters) conducted at Harvard in 1962, 10 divinity school students were given psilocybin just before a Good Friday service. Eight reported a mystical experience. In the late 1980s, researcher and psychedelics advocate Rick Doblin interviewed seven of the students who’d taken the drug. All said that experience had shaped their lives and work in profound ways. But Doblin also found that several subjects experienced acute anxiety during their experiences. One participant had to be dosed with a powerful antipsychotic after he became convinced that he’d been chosen to announce the arrival of the Messiah and ran from the chapel.

In 2006, Johns Hopkins researchers tested whether psychedelics induce a mystical experience in healthy people. Thirty-six volunteers were given either a hallucinogen or a placebo at one session. In the second session, the pills were reversed. Six months later, the study participants said they were “more sensitive, compassionate, tolerant, to have increased positive relationships, an increased need to serve others,” according to a lead researcher. The doctors interviewed participants’ family members, friends and colleagues as well; they all confirmed that the study participants had become nicer and more pleasant.

The positive changes seen in this study persisted for at least 14 months. A third of the participants in the Hopkins study rated their psilocybin session as the most spiritually significant experience of their lives, even more important than the birth of a child or the death of a parent.

The 2006 study was published in the Journal of Psychopharmacology. In that issue, several prominent drug researchers were invited to comment; all praised the finding and called for additional research. Columbia University professor Herbert Kleber wrote that he saw “major therapeutic possibilities.”

In a 2011 study, 18 healthy volunteers were given four doses of psilocybin. The vast majority of participants reported prolonged positive changes in attitude and mood, feelings that lasted for at least 14 months. In follow-up research, scientists determined that many of the volunteers from both studies had undergone a change in personality, something that is supposed to remain relatively fixed after 30. Participants had become more open-minded, tolerant and interested in fantasy and imagination.

“People have certain fears and rigid perspectives and ways of seeing the world that often limit what they can do,” said Katherine MacLean, who led the personality research at Johns Hopkins. “A lot of people I saw go through the study as healthy people wanted to make certain changes in their life. And psilocybin helped them make these changes.”