Credit: Unsplash/CC0 Public Domain
People who
consume psilocybin-containing mushrooms—otherwise known as magic
mushrooms—typically undergo a surreal experience in which their sense of space,
time and self is distorted. Advocates have long argued that, under the right
conditions, psychedelic experiences can alleviate mental distress, and a
smattering of scientific studies suggests they may be right. Understanding
precisely how the drug affects the brain will help scientists and doctors
harness its therapeutic potential.
In a new study, researchers at Washington University
School of Medicine in St. Louis report that psilocybin, the active compound in magic mushrooms, temporarily scrambles a
critical network of brain areas involved in introspective thinking such as
daydreaming and remembering.
The findings provide a neurobiological explanation for
the drug's mind-bending effects and lay some of the groundwork for the
development of psilocybin-based therapies for mental illnesses such as
depression and post-traumatic stress disorder.
"There's a massive effect initially, and when it's gone, a pinpoint effect remains," said co-senior author Nico U. F. Dosenbach, MD, Ph.D., a professor of neurology.
This heat map of brain activity patterns shows
profound disturbance during an individual's experience after taking psilocybin.
Relatively stable patterns before and after the dose (blue and green hues) are
temporarily scrambled during the "trip" (red, orange and yellow
hues). Researchers at Washington University School of Medicine in St. Louis
report that psilocybin destabilizes a critical network of brain areas involved
in introspective thinking. The findings provide a neurobiological explanation
for the drug's mind-bending effects. Credit: Sara Moser/Washington University
"That's exactly what you'd want to see for a potential medicine. You wouldn't
want people's brain networks to be obliterated for days, but you also wouldn't
want everything to snap back to the way it was immediately. You want an effect
that lasts long enough to make a difference."
The study, available July 17
in Nature, creates a road map other scientists can follow to
evaluate the effects of psychoactive drugs on brain
function, potentially accelerating drug development efforts for any
number of psychiatric illnesses.
Psilocybin showed promise as a treatment for depression in the 1950s and
'60s, but restrictive federal drug policy in subsequent decades quashed nearly
all further research. In recent years, though, regulations have loosened, and
interest in the field has been revived.
"These days, we know a lot about the psychological effects and the molecular/cellular effects of psilocybin," said first author Joshua S. Siegel, MD, Ph.D., an instructor in psychiatry. "But we don't know much about what happens at the level that connects the two—the level of functional brain networks."
Researchers at Washington University School of
Medicine in St. Louis report that psilocybin destabilizes a critical network of
brain areas involved in introspective thinking. The findings provide a
neurobiological explanation for the drug’s mind-bending effects. Credit: Sara
Moser/Washington University
To fill that gap, Siegel pulled together a team including Dosenbach, who is
an expert in brain imaging, and co-senior author Ginger E. Nicol, MD, an
associate professor of psychiatry who has experience running clinical trials
with controlled substances.
Together, they devised a way to visualize the impact of psilocybin on
individual participants' functional brain networks—neural communication
pathways that connect different brain regions—and to correlate changes in these
networks with subjective experiences.
The team recruited seven healthy adults to take
a high dose of psilocybin or methylphenidate, the generic form of Ritalin,
under controlled conditions. Because psychedelic trips carry the risk of users
having negative or scary experiences, a pair of trained experts stayed with
each participant throughout the experience.
The experts helped prepare the participants for what they were likely to
experience, provided guidance and support during each experiment, and helped
the volunteers process what had occurred afterward. Each participant underwent
an average of 18 functional MRI brain scans in the days to weeks before, during
and up to three weeks after their experiences with psilocybin. Four
participants returned six months later to repeat the experiment.
Psilocybin caused profound and widespread—yet not permanent—changes to the
brain's functional networks. In particular, it desynchronized the default mode
network, an interconnected set of brain areas that, ordinarily, are
simultaneously active when the brain is not working on anything in particular.
After falling out of sync, the network re-established itself when the acute
effects of the drug wore off, but small differences from pre-psilocybin scans
persisted for weeks. The default mode network remained
stable in people who received methylphenidate.
"The idea is that you're taking this system that's fundamental to the
brain's ability to think about the self in relation to the world, and you're
totally desynchronizing it temporarily," Siegel said. "In the short
term, this creates a psychedelic experience. The longer-term consequence is
that it makes the brain more flexible and potentially more able to come into a
healthier state."
Normally, each individual's functional brain network is as distinctive as a
fingerprint. Psilocybin distorted brain networks so thoroughly that individuals
could no longer be identified until the acute affects wore off.
"The brains of people on psilocybin look more similar to each other
than to their untripping selves," Dosenbach said. "Their
individuality is temporarily wiped out. This verifies, at a neuroscientific
level, what people say about losing their sense of self during a trip."
During the experience, participants were asked to rate their feelings of
transcendence, connectedness and awe using the validated Mystical Experience
Questionnaire. The magnitude of the changes to the functional networks tracked
with the intensity of each participant's subjective experience.
"We were able to get very precise data on the effects of the drug in
each individual," Nicol said.
"This is a step toward precision clinical trials. In psychiatry, we
often don't know who should get a particular medicine and how much or how
often. As a result, we end up prescribing one medicine after another, tinkering
with the dosage, until we find something that works. By using this
approach in clinical trials, we can identify the factors
that determine who benefits and who doesn't, and make better use of the
medicines we have."
Nicol, Siegel and Dosenbach emphasize that people should not interpret their study as a reason to self-medicate with psilocybin. The drug is not approved by the Food and Drug Administration (FDA) as a treatment for depression or any other condition, and there are risks to taking it without the supervision of trained mental health experts.
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