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Study offers new explanation for how psychedelic drugs work

The fascinating realm of neuroscience and psychedelic drugs has long been entranced by the prospect of unlocking the brain’s “critical periods” – developmental stages where the mammalian brain exhibits heightened sensitivity to environmental cues.

This sensitivity can shape and mold various brain functions, much like the pliable clay in a potter’s hand. A recent study from Johns Hopkins Medicine reveals that psychedelic drugs may hold the key to this unlocking process, albeit with differing durations.

This fascinating research, published in the prestigious journal Nature on June 14, shifts the understanding of how psychedelic drugs function.

The research also expands the potential therapeutic implications of these substances, extending beyond the commonly studied conditions such as depression, addiction, and post-traumatic stress disorder, to other maladies like stroke and deafness.

“Critical periods play a variety of essential roles, from assisting birds in mastering their melodies, to aiding humans in learning new languages, relearning motor skills after a stroke, and determining which eye asserts dominance over the other,” says Gül Dölen, M.D., Ph.D., associate professor of neuroscience at the Johns Hopkins University School of Medicine. She likens the brain’s critical period to a receptive window of opportunity that eventually shuts, reducing the brain’s openness to fresh learning.

Studying the deeper impact of psychedelic drugs

Dölen’s lab, with its expertise in the study of social behavior, has been delving into the effects of psychedelic drugs on reopening these vital developmental stages. Their 2019 research discovered that MDMA, a psychedelic known for its love-boosting and social enhancing effects, could pry open a critical period in mice.

It was initially believed that the prosocial properties of MDMA facilitated the reopening of the critical period. However, Dölen’s team encountered a surprise when they found that other psychedelics lacking prosocial properties were equally capable of unlocking these critical phases.

The researchers widened the scope of their investigation, turning their attention to five psychedelic drugs – ibogaine, ketamine, LSD, MDMA, and psilocybin. These substances, renowned for their ability to warp normal perceptions and trigger profound self-discovery, were tested on adult male mice using a well-established behavioral experiment.

How the study on psychedelic drugs was conducted

The researchers trained the mice to form associations between one environment linked to social interaction and another associated with solitude. By observing the time mice spent in each environment after administering a psychedelic drug, they gauged if the drug reopened the critical learning period in the adult mice. This social reward learning behavior is typically ingrained in juvenile mice.

Intriguingly, the results showed a variation in the reopening duration across different substances. Ketamine kept the social reward learning period active for 48 hours, psilocybin extended it to two weeks, while MDMA, LSD, and ibogaine sustained it for two, three, and four weeks, respectively. This duration aligns loosely with the self-reported acute effects of each psychedelic drug in humans.

Dölen points out that the varying lengths of these acute effects could explain the differing timeframes for each drug’s impact on reopening the critical period. She suggests that the post-treatment period could offer a valuable window of opportunity for maintaining the learning state.

Drawing a parallel to open heart surgery, Dölen recommends this period as an ideal time for healing and learning, particularly in the face of chaotic and busy lifestyles.

Taking the study to the molecular level

The researchers went a step further to examine the molecular mechanisms impacted by these drugs. Initially, they scrutinized a binding point, or receptor, for the neurotransmitter serotonin in mouse brain cells. They found that while LSD and psilocybin employed this receptor to unlock the critical period, MDMA, ibogaine, and ketamine did not.

Finally, they turned their attention to ribonucleic acid (RNA) to investigate other molecular pathways. They discovered differential expression among 65 protein-producing genes during and after the opening of the critical period. This means that these genes, responsible for producing proteins, were either turned on or off at varying levels in the mice’s cells.

Interestingly, about 20% of these genes are involved in maintaining or repairing the extracellular matrix – a sort of biological scaffolding that supports brain cells.

This is significant, as these brain cells are specifically located in the nucleus accumbens, an area associated with social learning behaviors that respond to rewards. In other words, the psychedelic drugs appear to influence these genes, which in turn modulate social learning behaviors.

Psychedelic drugs study results offer profound implications

The implications of this are profound. Not only does this research broaden our understanding of how psychedelics affect the brain, but it also offers potential new approaches for treating a variety of conditions.

By reopening critical periods in the brain, it may be possible to facilitate learning and recovery processes, as seen in the mice, with potential applications in the treatment of conditions like stroke or deafness.

The work of Dölen and her team marks a significant advancement in our understanding of the interplay between psychedelic drugs and the mammalian brain. While the research is still in its early stages, the evidence suggests that these drugs could hold significant therapeutic potential, opening new avenues in the field of neuroscience and mental health.

Nevertheless, as with all scientific findings, these results will need to be verified and expanded upon in further studies. In the meantime, the world of neuroscience eagerly awaits the unfolding of this enthralling narrative, the story of how our brains might be unlocked by the power of psychedelic drugs.

More about psychedelic drug therapy

Psychedelic drug therapy refers to the use of psychedelic substances as part of a therapeutic process. Psychedelics are substances that can alter cognition, perception, and mood, often leading to a deepened understanding of the self and the world around. Substances such as psilocybin (from magic mushrooms), LSD (lysergic acid diethylamide), MDMA (3,4-Methylenedioxymethamphetamine), and ayahuasca are being increasingly studied for their potential therapeutic uses.

Various different forms of psychedelic therapy

Psychedelic therapy can take various forms, but it generally involves one or several supervised sessions where the individual takes a psychedelic substance in a controlled and safe setting.

These sessions are typically accompanied by counseling or psychotherapy, both before and after the session, to help the individual prepare for the experience and to integrate what they have learned or felt during the experience.

The therapeutic effects of psychedelics are thought to be due, in part, to their ability to temporarily dissolve one’s normal sense of self (or “ego”), leading to a state of “ego-dissolution” or “ego-death.” This state can facilitate a new perspective on previously ingrained patterns of thought, emotion, and behavior, potentially leading to lasting changes in these patterns.

Potential Therapeutic Uses

Depression and Anxiety

Various trials have explored the use of psychedelic drugs, such as psilocybin and LSD, in treating depression and anxiety. This path is especially useful when these conditions are resistant to conventional treatment methods. In many cases, patients have reported significant improvements, often after just a single dose.


There is ongoing research on the use of psychedelics like psilocybin, LSD, and ayahuasca to treat various forms of addiction, including alcoholism and nicotine addiction.

Post-Traumatic Stress Disorder (PTSD)

Particularly with the use of MDMA, psychedelic therapy has shown promise in helping individuals with PTSD. MDMA is believed to reduce fear and increase feelings of trust, helping individuals to process traumatic memories in a therapeutic context.

End-of-life distress

Studies have shown that psilocybin and LSD can significantly reduce anxiety and depression in patients with life-threatening cancer, improving their quality of life.

Despite the potential benefits, therapy using psychedelic drugs is not without risks. Psychedelics can lead to uncomfortable or even terrifying experiences, commonly referred to as “bad trips”.

They can also interact with other substances or medications and are not advised for individuals with a history of psychosis or certain other mental health conditions. As such, this type of therapy should only be undertaken under the supervision of a trained professional.

Psychedelic therapy is still in a somewhat experimental stage, but quickly gaining momentum. While it’s been decriminalized or legalized in some jurisdictions, in many parts of the world it remains illegal. However, research is ongoing, and interest in this type of therapy is growing, both within the scientific community and beyond.

It’s important to note that while the results of studies on psychedelic therapy are promising, more research is needed to understand the long-term effects, appropriate dosage levels, and the mechanisms by which these substances operate. It’s also crucial that this therapy is performed in a controlled, safe, and supportive environment, and is seen as part of a broader therapeutic process, rather than a standalone solution.

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