Psychedelic Drug MDMA May Reawaken ‘Critical Period’ in Brain to Help Treat PTSD

Johns Hopkins neuroscientists have found that
the psychedelic drug MDMA reopens a kind of window, called a “critical
period,” when the brain is sensitive to learning the reward value of
social behaviors. The findings, reported April 3 in Nature, may explain why MDMA may be helpful in treating people with post-traumatic stress disorder (PTSD).

Critical periods were first described in the 1930s in snow geese.
About 24 hours after a gosling hatches, if mother goose is nowhere to be
found, the hatchling will bond with an object, including non-living
ones. Yet, if mother goose disappears 48 hours after her gosling
hatches, the critical period is over, and the hatchling won’t bond to an

There is evidence for critical periods that smooth the way for development of language, touch and vision.

For the current study, neuroscientist Gül Dölen
says, “We wanted to know if there was a critical period for learning
social reward behaviors, and if so could we reopen it using MDMA, since
this drug is well-known to have prosocial effects.”

Dölen and her team studied groups of mice in enclosures with
different bedding. They put several mice together in one enclosure with
one type of bedding for 24 hours and, in the next 24 hours, put the same
mice by themselves in another enclosure with a different type of
bedding. The mice began to associate certain types of bedding with
isolation or companionship. Then, they let the mice wander between
enclosures with the two types of bedding and tracked how long the mice
spent in each enclosure. The more time the mice spent in the bedding
linked to their companions indicated more social reward learning.

“It’s why people gather around the water cooler,” says Dölen,
assistant professor of neuroscience at the Johns Hopkins University
School of Medicine. People are conditioned to know that the water cooler
is an optimal place to chitchat with companions.

In their experiments, Dölen and her colleagues found that the
critical period for social reward learning in mice is around puberty and
wanes once they become mature adults. To determine if they could reopen
the critical period, the scientists gave MDMA to mature mice, waited 48
hours for the drug to be washed out of their system, and observed how
the mice explored their enclosure and behaved with other mice in the
enclosure. Following the treatment with MDMA, most of the animals
responded to social interactions the same way as juveniles, by forming a
positive association between social interactions and the bedding. This
effect lasted for at least two weeks after the MDMA treatment, and it
was not observed in mice given saline injections.

“This suggests that we’ve reopened a critical period in mice, giving
them the ability to learn social reward behaviors at a time when they
are less inclined to engage in these behaviors,” says Dölen.

Dölen and her postdoctoral student and first author of the current
study, Romain Nardou, also observed that MDMA works to reopen the
critical period only if the drug is given to mice when they are with
other mice, not if it is given to mice while they are alone. This
suggests that reopening the critical period using MDMA may depend on
whether the animals are in a social setting, say the scientists.

The mice maintained their ability to learn the rewards of social
behavior for up to two weeks from the time they were given MDMA. During
this time, Dölen and her colleagues also found that the brains of the
mice had corresponding responses to oxytocin, known as the “love
hormone,” which is made in the hypothalamus and acts in the brain as a
signal between neurons that encode information about social rewards.
They found these responses by looking more closely at synapses, the
spaces between brain cells called neurons. Their experiments showed
that, in mature mice given MDMA, oxytocin triggers signaling in the
synapses that encodes learning and memory, which does not typically
happen in mature mice.

Dölen says that opening the critical window for social reward
behavior may also have implications for treating psychiatric conditions.
A strong bond between a psychotherapist and patient is well-known to be
important for successful treatment. If MDMA reopens the critical period
for social reward learning in humans in the same way it does for mice,
then it could explain why the drug has been successful in treating
people with PTSD, perhaps by strengthening the psychotherapist-patient

MDMA has been designated by the U.S. Food and Drug Administration as a
“breakthrough therapy” for PTSD, meaning that the agency will
fast-track the development and review of clinical trials to test it.
However, the researchers caution that MDMA may not work for every
psychiatric condition linked to social behaviors.

“As we develop new therapies or determine when to give these
therapies, it’s critical to know the biological mechanism on which they
act,” says Dölen.

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