Unlocking the Mind: How Psychedelic Drugs Reset the Brain and Offer Promising Mental Health Treatments

Psychedelic drugs have shown promise in treating various mental-health conditions, although researchers have yet to fully comprehend their powerful therapeutic effects. A recent study conducted on mice suggests that psychedelics operate in a similar manner by resetting the brain to a more receptive state, allowing it to absorb new information and establish crucial connections between neurons. These findings raise the possibility that psychedelic drugs could bring about long-term changes in behavioral, learning, and sensory systems that are disrupted in mental-health conditions. However, scientists emphasize the need for further research to understand how these drugs remodel brain connections.

The study, published in Nature on June 14, reveals that psychedelics such as MDMA, ketamine, and psilocybin (the active ingredient in magic mushrooms) produce mind-altering effects and have the potential to relieve conditions like depression, addiction, and other challenging-to-treat disorders. Each compound affects a distinct biochemical pathway in the brain during the short-term experience, leading researchers to question why these drugs share the ability to provide long-term benefits.

To investigate this, a team of neuroscientists led by Gül Dölen from Johns Hopkins University studied how psychedelics impact social behavior in mice. They discovered that mice have an adolescent "critical period" during which they can associate socializing with positive feelings. The critical period ends as they transition into adulthood. By training the mice to associate different rooms in their enclosure with social interaction and solitude, the scientists could assess how psychedelics influenced the rodents' room preferences, which served as a proxy for examining the drug's effect on the critical period.

In a previous study, Dölen's team found that administering MDMA to adult mice in the presence of other mice reopened the critical period, making the MDMA-treated animals more inclined to sleep in the social room compared to untreated mice. This aligns with MDMA's known ability to promote bonding in animals and humans.

For the recent study, the researchers administered MDMA or one of four other psychedelic drugs (ibogaine, LSD, ketamine, and psilocybin) to adult mice. The mice that received any of the psychedelic drugs showed a greater preference for the social room compared to the untreated mice, indicating that each drug could reopen the critical period.

However, when mice were given enough ketamine to render them unconscious and unaware of their companions, they did not show a preference for the social room. This suggests that the drugs only open the social critical period when taken in a social context. Each drug had a different duration of critical period reopening, ranging from one week for ketamine to over four weeks for ibogaine.

Furthermore, the researchers examined the mice's brains and found that in certain regions, neurons became more sensitive to oxytocin, often referred to as the "love hormone." Dölen believes that the drugs induce a state called metaplasticity in the neurons, making them more responsive to stimuli such as oxytocin. This state increases the likelihood of rewiring and forming new connections, indicated by the neurons' expression of genes involved in regulating a protein matrix on their surface. Dölen suggests that modifying this matrix could facilitate the growth of neuronal branches and the establishment of new connections.

Dölen proposes that psychedelics act as a master key capable of unlocking various critical periods, not limited to sociability, by inducing metaplasticity in neurons. The specific outcome depends on the context in which the drugs are taken, such as the level of social engagement. These results indicate a mechanistic relationship between critical period reopening and the altered state of consciousness shared by all psychedelics.

Takao Hensch, a neurologist from Harvard University, views the study as pioneering for elucidating the biological mechanisms underlying the effects of psychedelic drugs. He believes that understanding the cellular impact of these drugs could hold the key to reopening brain plasticity and reversing what was previously considered irreversible during critical periods. Hensch suggests that while the study focuses on social behavior, the effects of these drugs should be further investigated in other brain regions.

On the other hand, David Olson, a biochemist from the University of California, Davis, remains skeptical. He suggests that the drugs might alter physical connections between neurons in specific brain regions rather than inducing metaplasticity that increases the neurons' susceptibility to environmental stimuli.

Currently, Dölen and her team are exploring whether psychedelic drugs can reopen critical periods in other areas, such as the motor system. If successful, this research could extend the period in which individuals who have experienced strokes can benefit from physical therapy, as current treatments are only effective in the initial months after a stroke.

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