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MDMA May Reopen Critical Period for Social Reward Learning

April 15, 2019

A single dose of the psychedelic drug methylendioxymethamphetamine (MDMA) reopens the critical period for learning the reward value of social behaviors, which may explain why the drug has been successful in treating patients with post-traumatic stress disorder (PTSD), according to a study published online in Nature.

With MDMA considered a breakthrough therapy for PTSD, the US Food and Drug Administration is prioritizing clinical trials testing the drug.

“As we develop new therapies or determine when to give these therapies, it’s critical to know the biological mechanism on which they act,” said neuroscientist Gül Dölen, MD, PhD, assistant professor of neuroscience at the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Phase 3 Trials to Test MDMA-Assisted Psychotherapy for PTSD

In studies involving mice, Dr. Dölen and colleagues determined the critical period for learning social rewards is around puberty. To determine if they could reopen the critical period in adult mice, they administered a single dose and waited 48 hours for the drug to leave their system.

For at least 2 weeks, the mice formed positive associations between social interactions and environments associated with companionship, researchers reported. Such behavior was not observed in mature mice who received saline injections.

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

A Turning Point for Psychedelics?

In mature mice given MDMA, oxytocin triggered signaling in the synapses that encode learning and memory—an occurrence not typical in mature mice, researchers explained.

Researchers believe the drug’s success in aiding PTSD treatment may be due to its ability to reopen the critical period for social reward learning in humans as well. By strengthening the bond between psychotherapist and patient, the drug may then allow more effective treatment to occur, they reasoned.

—Jolynn Tumolo


Nardou R, Lewis EM, Rothhaas R, et al. Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nature. 2019 April 3;[Epub ahead of print].

Psychedelic drug MDMA may reawaken ‘critical period’ in brain to help treat PTSD [press release]. Baltimore, Maryland: Johns Hopkins Medicine; April 4, 2019.

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