Psychedelic drugs have long fascinated neuroscientists due to their ability to reopen “critical periods” in the brain, when mammals are most receptive to environmental cues that influence brain development. A recent study conducted by researchers at Johns Hopkins Medicine sheds light on this phenomenon by showing that psychedelics can reopen critical periods, but with varying lengths of effectiveness. The findings, published in the journal Nature, not only explain how psychedelics work but also suggest their potential to treat a wider range of conditions beyond depression, addiction, and post-traumatic stress disorder, including stroke and deafness. Understanding these molecular mechanisms affected by psychedelics can lead to significant advancements in neuroscience and medical treatment.
Critical periods in brain development play crucial roles in various functions, such as language acquisition, motor skill relearning after a stroke, and establishing dominance of one eye over the other. These periods offer opportunities for the brain to learn from the environment before becoming less receptive to new information. Recognizing the importance of critical periods, the research team led by Gül Dölen, MD, Ph.D., associate professor of neuroscience at Johns Hopkins University School of Medicine, sought to investigate how psychedelics can reopen these critical periods.
In a previous study, Dölen’s team discovered that MDMA, a psychedelic drug known for its prosocial properties, could open a critical period in mice. However, in the current study, the researchers were surprised to find that other psychedelic drugs without prosocial properties, such as ketamine, LSD, psilocybin, and ibogaine, also reopened critical periods. This led them to examine the reopening potential of these five psychedelic drugs.
Using behavioral tests on adult male mice, the researchers trained the mice to associate a social interaction-related environment with positive reinforcement and another environment related to isolation. By comparing the time spent by the mice in each environment after administering the psychedelic drugs, the researchers could determine if the critical period had reopened. The results showed that the duration of the critical period varied among the different drugs. Ketamine’s effect lasted for 48 hours, while psilocybin extended the critical period for two weeks. MDMA, LSD, and ibogaine maintained the critical period for two, three, and four weeks, respectively. Interestingly, the length of the critical period in mice corresponded roughly to the average time people report experiencing the acute effects of the drugs.
Investigating the molecular mechanisms involved, the researchers focused on the serotonin receptor, a binding site for the neurotransmitter serotonin. They found that LSD and psilocybin used the serotonin receptor to open the critical period, whereas MDMA, ibogaine, and ketamine did not. Additionally, the research team examined the expression of genes involved in protein production in mouse cells. They discovered differences in gene expression during and after the critical period opened, with approximately 20% of the genes regulating proteins related to the maintenance and repair of the extracellular matrix in the nucleus accumbens, an area associated with social learning behaviors and reward response.
The findings of this study have significant implications for the medical field. Recognizing that the critical period represents an opportunity for learning and healing, clinicians could consider the period following psychedelic drug administration as a time for post-treatment integration and reflection. By providing a conducive environment for patients to process their experiences, similar to the care given after open-heart surgery, clinicians may enhance the therapeutic effects of psychedelic treatments.
In conclusion, this study sheds light on the unique ability of psychedelics to reopen critical periods in the brain. The varying lengths of these periods and their correlation with the acute effects of psychedelic drugs provide insights into their mechanisms of action. By understanding these molecular processes, scientists can explore the potential of psychedelics to treat a broader range of conditions, beyond mental health disorders. This research opens up new possibilities for medical interventions and offers a deeper understanding of how the brain learns and adapts to its environment.
Additional piece:
Expanding the Boundaries of Neuroscience: Psychedelics and Human Potential
Over the past few decades, the study of psychedelics has experienced a renaissance. Once dismissed as substances associated with counterculture movements, these mind-altering compounds are now captivating the attention of scientists, researchers, and therapists worldwide. The recent study conducted by researchers at Johns Hopkins Medicine not only enhances our understanding of psychedelics’ ability to reopen critical periods in the brain but also broadens the scope of their potential applications.
Traditionally, psychedelics have been associated with the treatment of mental health disorders, such as depression, addiction, and post-traumatic stress disorder. However, the findings from the study suggest that their therapeutic potential extends far beyond these conditions. By reopening critical periods in the brain, psychedelics could provide groundbreaking insights into the treatment of stroke and hearing loss. Imagine a future where a single dose of a psychedelic drug could help individuals recover motor skills after a stroke or improve auditory perception in individuals with hearing impairments.
Furthermore, the study delves into the molecular mechanisms affected by psychedelics, providing valuable knowledge for scientists and researchers in the field of neuroscience. Understanding how these compounds interact with the brain’s receptors and influence gene expression opens up new avenues for targeted drug development and personalized medicine. By exploring the genetic and molecular changes induced by psychedelics, we can uncover valuable clues about the underlying mechanisms of neurological disorders and potentially develop novel treatments.
While the study focuses on mice, the implications for human application are promising. As researchers continue to investigate the therapeutic potential of psychedelics, human clinical trials are increasingly demonstrating their efficacy. In recent years, psychedelic-assisted therapies have shown remarkable results in treating treatment-resistant depression and end-of-life anxiety in cancer patients. The reopening of critical periods in the brain could be a game-changer in mental health treatment, offering a unique opportunity for individuals to break free from deeply ingrained patterns and traumas.
However, it is essential to proceed with caution and ensure the responsible and ethical use of these substances. The psychedelic experience is profound and can be overwhelming for individuals without proper guidance and support. The integration period following a psychedelic experience is crucial, as it allows individuals to make sense of their journey and integrate the insights gained into their daily lives. Therapy sessions, support groups, and community networks play a vital role in maximizing the benefits of psychedelic-assisted therapies and ensuring the long-term well-being of individuals.
As society embraces a more holistic approach to health and well-being, psychedelics are poised to play a pivotal role in the future of medicine. The potential to enhance brain plasticity, facilitate emotional healing, and unlock hidden potentials within ourselves is awe-inspiring. However, as we embark on this journey, it is essential to maintain a spirit of curiosity, respect, and responsibility. By combining scientific rigor, compassionate care, and a commitment to ethical practices, we can unleash the transformative power of psychedelics and empower individuals on their path towards growth, healing, and self-discovery.
Summary:
Neuroscientists at Johns Hopkins Medicine have conducted a study on mice that shows psychedelics can reopen critical periods in the brain. These critical periods are crucial for brain development and learning. The study examined the effects of five different psychedelic drugs, including ketamine, LSD, psilocybin, MDMA, and ibogaine, and found that each drug had varying lengths of critical period reopening. The researchers also explored the molecular mechanisms affected by psychedelics and discovered differences in gene expression during and after the critical period opened. The study’s findings have significant implications for the potential use of psychedelics in treating conditions beyond depression, addiction, and post-traumatic stress disorder, such as stroke and deafness. The research provides new insights into how psychedelics work and opens up possibilities for further exploration in neuroscience and medical treatment.
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Neuroscientists have long sought ways to reopen “critical periods” in the brain, when mammals are most sensitive to cues from their environment that can influence periods of brain development. Now, Johns Hopkins Medicine researchers say a new study in mice shows that psychedelics are linked by their common ability to reopen critical periods, but differ in length of critical period, from two days to four weeks with a single dose.
The findings, published June 16 in the journal Nature, provide a new explanation for how psychedelics work, the scientists say, and suggest potential to treat a broader range of conditions, such as stroke and deafness, beyond those found in current studies of the drugs, such as depression, addiction and post-traumatic illness. stress disorder. The scientists are also providing a new look at the molecular mechanisms affected by psychedelics.
Critical periods have been shown to perform functions such as helping birds learn to sing and helping humans learn a new language, relearning motor skills after stroke, and establishing dominance of one eye over the other. .
“There is a window of time in which the mammalian brain is much more susceptible and open to learning from the environment,” says Gül Dölen, MD, Ph.D., associate professor of neuroscience at Johns University School of Medicine. Hopkins. “This window will close at some point, and then the brain becomes much less open to new learning.”
Building on his lab’s experience studying social behavior, Dölen’s team has been investigating how psychedelics work by reopening these critical periods. In 2019, her team discovered that MDMA, a psychedelic drug that arouses feelings of love and sociability, opens a critical period in mice.
At the time, Dölen thought that MDMA’s prosocial properties paved the way for opening the critical period, but he says his team was surprised to find in the current study that other psychedelics without prosocial properties could also reopen critical periods.
For the current study, Dölen’s team looked at the reopening potential of five psychedelic drugs (ibogaine, ketamine, LSD, MDMA, and psilocybin) that have been shown in numerous studies to be able to change normal perceptions of existence and allow a sense of discovery about oneself. or the world.
The research team conducted a well-established behavioral test to understand the ease with which adult male mice learn from their social environment. They trained mice to develop an association between an environment related to social interaction and another environment related to being alone. By comparing the time they spent in each environment after administering the psychedelic drug to the mice, the researchers were able to see if the critical period opened up in the adult mice, allowing them to learn the value of a social environment, a behavior that is normally learned when They are young. .
For mice given ketamine, the critical learning period for social reward remained open for 48 hours. With psilocybin, the open state lasted two weeks. For the mice given MDMA, LSD, and ibogaine, the critical period remained open for two, three, and four weeks, respectively.
The researchers say that the length of time that the critical period remained open in the mice appears to roughly parallel the average time that people report the acute effects of each psychedelic drug.
“This relationship gives us another clue that the duration of the acute effects of psychedelics may be the reason why each drug may have longer or shorter effects at the opening of the critical period,” says Dölen.
“The open state of the critical period may be an opportunity for a post-treatment integration period to maintain the learning state,” he adds. “Too often, after undergoing a procedure or treatment, people return to chaotic and busy lives that can be overwhelming. Clinicians may want to consider the time period following a dose of psychedelic drugs as a time to heal and learn, just like we do. for open-heart surgery.
Next, the scientists looked at the impact of psychedelic drugs on molecular mechanisms. First, in mouse brain cells, they examined a binding site, known as a receptor, for the neurotransmitter serotonin. The researchers 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 of DNA that represents which genes are expressed (make proteins) in mouse cells. The researchers found expression differences between 65 protein-producing genes during and after the critical period opened.
About 20% of these genes regulate proteins involved in the maintenance or repair of the extracellular matrix, a kind of scaffolding that encloses brain cells located in the nucleus accumbens, an area associated with social learning behaviors that respond to rewards.
No authors declared conflicts of interest related to this research under the policies of the Johns Hopkins University School of Medicine.
Funding for the research was provided by the Klingenstein-Simons Foundation, the Kavli Neuroscience Discovery Institute Distinguished Postdoctoral Fellowship, the Johns Hopkins Provost Postdoctoral Fellowship Program, and the National Institutes of Health (R01MH117127, R01HD098184, R01AG066768, R01AG072305, K99NS122 085) .
Others who helped conduct the research included Romain Nardou, Edward Sawyer, Young Jun Song, Makenzie Wilkinson, Yasmin Padovan-Hernandez, Júnia Lara de Deus, Noelle Wright, Carine Lama, Sehr Faltin, Loyal Goff, and Genevieve Stein-O’Brien de Johns Hopkins.
https://www.sciencedaily.com/releases/2023/06/230614220630.htm
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