During key stages of brain growth, the brain is highly receptive to certain experiences. This allows it to quickly adapt in terms of how it's wired and how it behaves. These pivotal stages are called "critical periods" and are observed in almost every species. If an individual misses these experiences during these times, it can become challenging or even impossible to learn specific skills or functions later on. Examples include geese forming bonds, finches learning songs, and humans picking up language. There is also a critical period for learning social skills that ends in childhood. For a long time, brain scientists have been trying to find ways to revisit these periods to help treat various conditions. Recent research into psychedelics has highlighted its potential to reoopen these crucial stages of development, especially in terms of social reward learning, offering individuals a second chance to learn critical social skills they missed growing up.
MDMA reopens critical social reward learning period
In 2019, a study by Gül Dölen's team at Johns Hopkins showed that there's a specific developmental window in the nucleus accumbens that is regulated by oxytocin and which is crucial for social reward learning. Giving mice just one dose of MDMA could reactivate this crucial learning phase and enhance sensitivity to oxytocin. MDMA is often referred to as an "empathogen" because of its noticeable prosocial effects when consumed.
In this study, scientists evaluated how the social preferences of mice varied with age. They found that mice showed the highest level of social preference around 42 days, which corresponded to when they matured sexually. This preference then declines until the critical period closes at 98 days, which corresponds to mature adulthood. This social preference period was linked to the regulation of oxytocin-driven neural plasticity in the nucleus accumbens, which represents a primary mechanism establishing the crucial period for social reward learning.
Giving the mice MDMA re-opened their window for social reward learning in as little as 6 hours and remained open for up to two weeks. But by the end of the fourth week, it reverted back to its original state. The reopening of this learning window was driven by the stimulation of oxytocin receptors in the nucleus accumbens.
Prior to this research, Gül Dölen's lab had examined the behaviour of the California two-spot octopus, Octopus bimaculoides are known for their antisocial tendencies. The team originally housed these octopuses individually under separate flower pots, understanding that they could harm each other if they were given the chance. However, after they were given MDMA, they became more sociable and drawn to communal areas. This suggests that these creatures have the neural structures for social interaction, although these tendencies are typically dormant unless it is mating season.
Other psychelics also reopen the critical social reward learning period
In this latest study, Dölen's lab has found that psilocybin, ketamine, ibogaine, and LSD also reopen the critical social reward learning period, in addition to MDMA.
In mice, the critical period remained open for between 48 hours and four weeks, depending on the psychedelic.
Figure from Nardou et al. (2023)
In humans, the subjective effects of psychedelics vary from about 30 minutes to 72 hours. However, the therapeutic effects can last much longer, from a week to months and even years.
Why is this important?
The critical social reward learning period in childhood is when we learn appropriate social behaviour according to social norms. These include behaviours such as empathy, cooperation, community, tolerance, altruism, and civility, but can also include behaviours such as social anxiety, shyness and reservedness. During this critical period, we can also learn destructive behaviours that violate social norms, such as antisocial behaviour, deception, malevolence, and tit-for-tat. Being able to reopen this critical period gives us another opportunity to learn new social behaviours or correct inappropriate or destructive social behaviours. And it is during this open period that individuals may be more receptive to the therapist themselves.
Approximately 7% of the population grapple with social anxiety, which can profoundly limit various aspects of their lives, from voicing opinions in meetings to attending job interviews and social events. Between 1% and 4% are affected by anti-social personality disorder, with many more displaying antisocial tendencies. The potential to alleviate or even reverse these conditions is exciting. "These results [also] suggest that psychedelics could serve as a ‘master key’ for unlocking a broad range of critical periods for disorders (including autism, stroke, deafness and blindness) that might benefit from treatment with psychedelics."
Of course, any exploration in this domain must be approached with caution and under appropriate guidance.
Eric Edsinger, E, & Gül Dölen, A. (2018). A conserved role for serotonergic neurotransmission in mediating social behavior in octopus, Current Biology, 28, 3136-3142.e4, https://doi.org/10.1016/j.cub.2018.07.061.
Nardou R, Lewis E.M, Rothhaas R, et al. (2019). Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Nature: 569(7754):116-120. doi: 10.1038/s41586-019-1075-9.
Nardou, R., Sawyer, E., Song, Y.J. et al. (2023). Psychedelics reopen the social reward learning critical period. Nature 618, 790–798. https://doi.org/10.1038/s41586-023-06204-3
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