Neuroscientists have long sought techniques to reactivate critical periods in the brain when animals are more receptive to environmental cues that could alter brain development. According to a recent study in mice conducted by Johns Hopkins Medicine, psychedelic substances are related in their shared ability to reopen such important periods, but the range of time for which the critical period is open from two days to four weeks at a single dose.
The findings, published in the journal Nature, provide a new explanation for how psychedelic drugs work and suggest they may be useful in treating conditions other than depression, addiction and post-traumatic stress disorder, according to the researchers. Scientists have also taken a new look at the molecular pathways affected by psychedelics.
Critical times have been shown to help birds learn to sing and humans to acquire a new language, restore motor skills after a stroke and establish dominance of one eye over the other.
“There is a period when the mammalian brain is much more susceptible and open to learning from the environment,” said Gul Dolen, M.D., Ph.D., associate professor of neuroscience at the Johns Hopkins University School of Medicine, adding, “At some point this window closes and then the brain becomes much less open to new learning.”
Drawing on her lab’s experience studying social behavior, Dolen’s team investigated how psychedelic drugs work by reopening these critical periods. In 2019, her team found that MDMA, a psychedelic drug that induces feelings of love and companionship, opens a critical period in mice.
At the time, Dolen thought MDMA’s prosocial properties eased the way to open the critical period, but her team was surprised to find in the current study that other psychedelic drugs without prosocial properties could also reopen the critical periods.
For this study, Dolen’s team looked to rediscover the potential of five psychedelic drugs ibogaine, ketamine, LSD, MDMA, and psilocybin—which have been shown in multiple studies to alter the normal perception of existence and enable a sense of self-discovery world.
The research team conducted a well-established behavioral test to understand how easily adult male mice learn from their social environment. They trained mice to make an association between an environment associated with social interaction and another environment associated with being alone.
By comparing the time spent in each environment after the mice were given the psychedelic drug, the researchers were able to determine whether a critical period opened up in the adult mice, allowing them to learn the value of the social environment – a behavior normally learned as juveniles.
In ketamine-treated mice, the critical period of social reward learning in mice remained open for 48 hours. With psilocybin, the open state lasted two weeks. In mice given MDMA, LSD, and ibogaine, the critical period remained open for two, three, and four weeks.
The researchers say that the time the critical period remained open in the mice appeared to be roughly the same as the average time it took people to self-report the acute effects of each psychedelic drug.
“This relationship gives us another clue that the duration of the acute effects of psychedelic drugs may be why each drug may have a longer or shorter effect on the opening of the critical period,” Dolen said.
“The open state of the critical period can be an opportunity for a post-treatment integration period to maintain a state of learning,” she said, adding, “Too often, people return to their chaotic, busy lives after a procedure or treatment, which can be overwhelming. Clinicians may want to consider the period of time after a psychedelic drug dose as a time for healing and learning, much like we do with open-heart surgery.”
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