Learn Like Babies (Part 1): Psychedelics And Critical Periods

We’re evaluating a study published in Nature in 2023. Titled “Psychedelics reopen the social reward learning critical period”, it examines whether psychedelics…reopen the social reward learning critical period. I love when study titles are straightforward.

What is the “Critical Period” & What’s the Benefit of Opening It?

Critical periods are crucial windows in time when the brain is exceptionally receptive to new information. During certain parts of brain development, the nervous system shows heightened sensitivity to certain stimuli. These periods play a vital role in acquiring essential skills such as language development, motor skills like walking, and forming strong bonds with parents. For instance, it’s during a critical period that babies learn to recognize faces and interpret facial expressions, while young animals learn crucial survival behaviors from their parents. Neuroscientists believe that there are critical periods for various cognitive functions, and once these windows close, the brain becomes less adaptable to new learning experiences.

Re-opening critical periods is of interest to neuroscientists as it has potential for therapeutic benefit. Opening critical periods may accelerate learning by making the brain highly receptive to new information. It enhances adaptability, enabling individuals to adjust more effectively to their surroundings and develop resilience. Additionally, skills learned during critical periods tend to be deeply ingrained, resulting in more proficient abilities later in life. Furthermore, opening critical periods may facilitate rehabilitation after brain injuries or neurological disorders, promoting recovery and functional improvement. Lastly, targeted interventions during critical periods can be more effective in addressing developmental delays or learning difficulties, maximizing the chances of successful intervention and overall improvement.

Psychedelics show potential for re-opening critical periods. A recent study by the Dölen lab showed MDMA can reopen a critical period for “social reward learning”. One thought is that this could be due to MDMA’s status as an empathogen – a substance which produces acute subjective effects that can be distinctly labeled as “prosocial”, such as increased empathy and other prosocial emotions. Other psychedelics such as psilocybin, ketamine, and LSD are not considered empathogens. Emphasis on “acute” and “distinctly”. Other psychedelics may produce similar prosocial emotions and feelings, but MDMA is in a tier above – these effects come upon you more rapidly, and are very prosocial.

If MDMA’s ability to reopen learning critical periods is related to this property, it would cast doubt on the potential of other psychedelics to reopen these windows.

But, another thought is that MDMA reopens learning critical periods because MDMA induces an altered state of consciousness. I’m not breaking news here, but in case you didn’t know, those other psychedelics mentioned above also induce an altered state of consciousness. And if it’s this quality that allows MDMA to reopen learning critical periods (rather than its empathogenic effects), then one could imagine other psychedelics may also have this capability.

Study Method

This study aimed to find an answer to the question posed above – is it the empathogenic effects of MDMA that allow it to reopen critical periods (such as the social reward learning critical period), or is it because MDMA induces an altered state of consciousness? (Or are both assumptions incorrect?)

Researchers administered doses of psychedelics to adult mice and assessed the effects. They used a tool called the social reward conditioned place preference (sCPP) assay to determine if the critical period for social reward learning was reopened. Conditioned place preference, or CPP, is a learned association between a condition and a cue. In this study, the “condition” is social (interacting with other mice) or isolation, and the “cue” is the type of bedding the mice were exposed to. Here’s how this played out, pre-psychedelic or saline administration:

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1. Male mice were housed in a cage with corncob bedding until a specific age for the study.

2. A monitoring chamber was created with plexiglass divided into two equal-sized zones, each containing different types of bedding.

3. 48 hours before testing, mice received injections of saline (placebo), psilocybin, LSD, ketamine, or ibogaine.

4. The “pre-test” involved exposing mice to the chamber one at a time for 30 minutes to freely explore and note preferences for each bedding zone, scored on a scale of 0 to 1,800 (don’t ask lol). A “900” score meant that mouse spent his time between both cages equally

5. “Social conditioning” for 24 hours involved mice spending time with cage mates on one type of bedding, followed by 24 hours of “isolation conditioning” alone on the other bedding.

6. After the isolation conditioning period, a 30-minute test was conducted to assess mice’s preference for the conditioned cues, scored on the same scale.

7. Researchers compared pre-test preferences with post-test preferences to determine if the social reward learning critical period was reopened.

Results

Psilocybin, LSD, ketamine, and ibogaine all re-opened the critical period, just like MDMA. This was shown when mice pre-treated with a psychedelic showed a preference for “social zone” versus the “isolation zone”. Saline, however, failed to do so.

Also interesting to note, the researchers tested and found no psychedelic had an effect on cocaine reward learning and amphetamine-induced locomotor sensitization, two addiction-like behaviors which can be induced by certain medications and substances.

What Comes Next?

There’s a lot to unpack in this study. In addition to exploring the potential for MDMA and other psychedelics to reopen the social reward critical learning period, the researchers also explored answers to questions such as:

• Once this window is reopened, how long is it open? Does this vary amongst different psychedelics?

• Do psychedelics induce metaplasticity or hyperplasticity?

• Is there a “universal mechanism” that explains how different psychedelics perform this similar function?

And, there are other conclusions from this study to discuss. But this seems like enough to digest for one newsletter. In my next article, I’ll continue breaking down details, results, and implications from this study. In the meantime, I encourage you to read the full article and let me know what you find interesting!