New findings from an animal study show that psychedelics open a ‘critical period’ of social reward learning in the brain, but that different psychedelics do so for different lengths of time.
This period differs in length from two days to four weeks, say Johns Hopkins researchers.
While psychedelics are currently being extensively researched for mental health indications and addiction, the researchers suggest that the findings from the study, which has been published in the journal Nature, show the potential of psychedelics to treat a wider range of conditions, such as stroke and deafness.
Critical learning periods
Research has so far shown that critical periods in the mammalian brain help to learn from the environment, for example, in humans, it can help them to learn a new language or relearn motor skills after a stroke.
Gül Dölen, M.D., Ph.D., associate professor of neuroscience at the Johns Hopkins University School of Medicine, stated: “There is a window of time when the mammalian brain is far more susceptible and open to learning from the environment. This window will close at some point, and then, the brain becomes much less open to new learning.”
Dölen’s team has been researching how psychedelic drugs work by reopening these critical periods, and, in 2019, found that MDMA opens a critical period in mice.
Initially, the team thought this was due to MDMA’s prosocial properties, however, the current study has revealed that other psychedelic drugs without prosocial properties could also reopen critical periods.
In this study, the researchers looked at the reopening potential of ibogaine, ketamine, LSD, MDMA and psilocybin.
The research team conducted a behavioural test to understand how easily adult male mice learn from their social environment, training the mice to develop an association between an environment linked with social interaction versus another environment connected with being by themselves.
The team compared the time spent in each environment after giving the psychedelic drug to the mice, enabling them to see if the critical period opened in the adult mice in order to learn the value of a social environment — a behaviour normally learned as juveniles.
The results showed that the critical period of social reward learning stayed open in the mice:
- Ketamine: 48 hours
- Psilocybin: Two weeks
- MDMA: Two weeks
- LSD: Three weeks
- Ibogaine: Four weeks
The researchers state that the length of time that the critical period stayed open in mice seems to roughly parallel the average length of time that people self-report the acute effects of each psychedelic drug.
“This relationship gives us another clue that the duration of psychedelic drugs’ acute effects may be the reason why each drug may have longer or shorter effects on opening the critical period,” said Dölen.
“The open state of the critical period may be an opportunity for a post-treatment integration period to maintain the learning state,” she adds. “Too often, after having a procedure or treatment, people go back to their chaotic, busy lives that can be overwhelming. Clinicians may want to consider the time period after a psychedelic drug dose as a time to heal and learn, much like we do for open heart surgery.”
Molecular mechanisms
To gain a deeper understanding of psychedelic drugs’ impact on molecular mechanisms the team examined a binding point in mice brain cells, known as a receptor, for the neurotransmitter serotonin.
They found that while LSD and psilocybin use the serotonin receptor to open the critical period, MDMA, ibogaine and ketamine do not.
To explore other molecular mechanisms, the research team turned to ribonucleic acid (RNA), a cousin to DNA that represents which genes are being expressed (producing proteins) in the mice’s cells.
They found expression differences among 65 protein-producing genes during and after the critical period was opened.
About 20% of these genes regulate proteins involved in maintaining or repairing the extracellular matrix — a kind of scaffolding that encases brain cells located in the nucleus accumbens, an area associated with social learning behaviours that are responsive to rewards.
