One of the hottest tickets at this year's Society for Neuroscience meeting in San Diego was a session on psychedelic drugs.
About 1,000 brain scientists squeezed into an auditorium at the San Diego Convention Center for the symposium, called Psychedelics and Neural Plasticity.
They'd come to hear talks on how drugs like psilocybin and MDMA can alter individual brain cells, can help rewire the brain, and may offer a new way to treat disorders ranging from depression to chronic pain.
"I was pleasantly surprised at the number of people," says Alex Kwan, a biomedical engineer at Cornell University who spoke at the session.
"In the last couple of years there has been a lot of public excitement about psychedelics," Kwan says. "The scientists are catching on now that we just don't know much about what these compounds do."
So during the session, Kwan and several other researchers shared what they are learning about the drugs.
Rewiring the brain
Kwan described his own work on how psilocybin, the active ingredient in magic mushrooms, seems to help the brain rewire by generating new connections between neurons.
A study of mice found that psilocybin altered dendrites, the branch-like structures that extend from a nerve cell and receive input from other cells.
Dendrites form connections through small protrusions known as dendritic spines. And in mice that got psilocybin, the size and number of these spines increased by about 10%, which allowed cells to form new connections.
"When we give mice a single dose of psilocybin, we can see those new connections form within a day," Kwan says. "And then they can last more than a month," which is the equivalent of many months in a human.
New connections are a critical part of the rewiring process known as brain plasticity, which allows the brain to learn and adapt.
"Psychedelics seem to elevate plasticity," Kwan says.
Brain plasticity may explain why a single dose of a psychedelic drug can have a long-lasting impact on disorders like anxiety, depression and PTSD.
"It can be months or years," says Dr. Gitte Knudsen a neurologist from University of Copenhagen in Denmark who spoke at the psychedelics session. "It's a stunning effect."
These long-term effects have been shown with drugs including psilocybin, LSD and DMT (ayahuasca), Knudsen says. In contrast, most existing psychiatric drugs need to be taken every day.
But psychedelic drugs have some drawbacks. They can cause nausea or produce hallucinations that are frightening or unpleasant.
"It can be a quite overwhelming experience to people," Knudsen says. "And for that reason, you need to prepare them for that, and you also need to be with them while they are in the experience."
Even when patients are well prepared for a session, Knudsen says, they may have mixed feelings afterward.
"When people have been through a psychedelic experience in my lab, they say, 'Wow this was amazing, this was just a fantastic experience,'" she says. "And you ask them, 'Well, would you like to come back next week for another session?' They say, 'Thank you, but no thank you.' "
Psychedelics in the mainstream
The fact that psychedelics were featured at the world's largest meeting of brain scientists suggests the drugs are poised to enter the scientific mainstream. That's a recent development.
Psychedelic research was popular in the 1950s but pretty much ended after the mid-1960s when the drugs were made illegal in the U.S. and Europe.
In the 1990s, a few researchers began cautiously studying how drugs like LSD, MDMA and psilocybin might help with psychiatric conditions like depression and PTSD.
And in 2016, a pair of studies published by prominent researchers "really piqued everyone's interest," says Dr. Joshua Gordon, who directs the National Institute of Mental Health.
Both studies found that a single treatment with psilocybin reduced anxiety and depression in cancer patients.
That has led to some large studies of psychedelics, including one published in The New England Journal of Medicine in November showing that psilocybin helped people with major depression who hadn't been helped by other treatments.
Studies like that one suggest that psychedelics "are going to be beneficial and useful" in treating psychiatric disorders, Gordon says.
But the effects found in large studies of psychedelics have been much less dramatic than in some of the earlier, smaller studies, Gordon says. Also, he says, some companies hoping to market psychedelics have overstated their benefits.
"There is a lot of hype," he says, "and a lot of hope."
ARI SHAPIRO, HOST:
The world of neuroscience is tuning in to psychedelic drugs. Researchers are studying how substances like magic mushrooms and ecstasy may help rewire the brains of people with depression, PTSD and chronic pain. NPR's Jon Hamilton reports.
JON HAMILTON, BYLINE: One of the hottest tickets at this year's Society for Neuroscience meeting in San Diego was a symposium on how psychedelic drugs affect the brain. Steven Grieco, a brain scientist at the University of California, Irvine, helped organize the session.
STEVEN GRIECO: There's probably a thousand or more people there. It seemed like every section and every chair of that entire room was filled up.
HAMILTON: A decade ago, research on psychedelics was still largely outside the scientific mainstream. But that's changing, says Alex Kwan of the biomedical engineering department at Cornell University.
ALEX KWAN: The scientists are catching on now. We just don't know much about what these compounds do and a lot of interest from young scientists who want to jump into this area.
HAMILTON: At the meeting, Kwan presented some of his own research, looking at how psychedelic drugs can help brain cells form new connections, a process known as plasticity.
KWAN: What it suggests is that psychedelic seems to elevate that type of plasticity potential to make that brain generate even a bit more connections.
HAMILTON: For example, a study of mice found that psilocybin altered dendrites, the part of a nerve cell that receives input from other cells. Kwan says psilocybin increased the number of spiny protrusions on dendrites, allowing them to make more connections.
KWAN: When we give mice a single dose of psilocybin, we can see those new connection form within a day, and then they last up to more than just over a month.
HAMILTON: That long-term rewiring suggests psychedelic drugs won't have to be taken every day like most current psychiatric medications.
Dr. Gitte Knudsen, a neurologist at the University of Copenhagen in Denmark, told the session that people who get psilocybin for anxiety and depression may only need one dose.
GITTE KNUDSEN: The stunning effects of psychedelics is that one of a few single doses can have such long-lasting impact. It could be months or even years. And that is what makes it such an interesting drug to look at.
HAMILTON: But Knudsen says in the first few hours after a dose, the drugs can produce mind-bending effects that are frightening or disturbing.
KNUDSEN: It can be a quite overwhelming experience to people. And for that reason, you need to prepare them for that. And you also need to be with them while they're in the experience.
HAMILTON: Knudsen says even when patients are prepared, they often have mixed feelings about the sessions.
KNUDSEN: When people have been through a psychedelic experience in my lab, they say, wow; this was amazing. This was just a fantastic experience. And you ask them, well, would you like to come back next week for another session - say, thank you, but no thank you.
HAMILTON: Psychedelic research was popular in the 1950s, but pretty much ended in the mid-1960s when governments began outlawing the drugs. In the 1990s, a few researchers began studying how drugs like LSD, MDMA and psilocybin might help with psychiatric conditions, including depression and PTSD. Dr. Joshua Gordon, who directs the National Institute of Mental Health, says just a few years ago, psychedelics got a big boost in credibility.
JOSHUA GORDON: The first study that really piqued everyone's interest was the end-of-life work - right? - where you can reduce people's anxiety about end-of-life issues using psychedelics.
HAMILTON: In 2016, two studies by prominent researchers showed that psilocybin helped people with anxiety and depression associated with a cancer diagnosis. That led to a series of small studies and then some large trials, showing that psychedelics really can help with conditions like depression and PTSD.
GORDON: When you start seeing large trials showing effects, then the skeptics, now, are even jumping on board.
HAMILTON: But the large studies haven't reproduced the spectacular results seen in some smaller trials. And Gordon says some companies hoping to market psychedelics are overpromising.
GORDON: There is a lot of hype. These drugs are probably going to be beneficial and helpful, but not really transformative drugs.
HAMILTON: Gordon thinks psychedelics probably won't revolutionize psychiatry, but they may help some people who haven't been helped by anything else. Jon Hamilton, NPR News.
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