A Single Psychedelic Dose Shows Weeks-Long Impact on Learning

A lab mouse investigates a food pellet as a part of a behavioral experiment studying learning and memory.

Researchers at the University of Michigan have reported that one dose of a psychedelic compound improved learning flexibility in mice, with effects lasting for at least two to three weeks!

The study tested 25CN-NBOH, a compound that targets serotonin 2A receptors. After receiving a single injection, mice were trained to follow a sequence to receive a food pellet. After several days, the rules of the task were reversed. Mice that had received the psychedelic adjusted to the new rules more effectively than those given saline.

Their improvements were seen in multiple ways. During the reversal phase, they made more correct moves, completed tasks more efficiently, and earned more rewards. These changes did not appear during the initial learning phase, suggesting that the compound specifically helped with adapting to new rules rather than with general learning.

This type of behavioral flexibility, often called cognitive flexibility, is a key function of the brain's prefrontal cortex. It is frequently reduced in people living with depression, PTSD, and some neurodegenerative conditions. Difficulty with changing habits or adapting to new information is common in these disorders.

Unlike many previous studies that measure short-term psychedelic effects, this study measured performance weeks after the treatment. This timing is important. It shows that the improvement was not tied to the acute effects of the drug but rather to longer-lasting changes in how the brain functions.

The study's results suggest that psychedelics might support brain plasticity in a way that could be useful for therapeutic interventions. For people facing conditions that reduce cognitive flexibility, strengthening this capacity could help with daily decision-making, planning, and adjusting to unexpected situations.

This study adds to a growing body of research showing that psychedelics can influence brain structure and behavior long after the drug has left the body. Rather than focusing only on symptom relief, future treatments might look toward supporting the brain’s capacity to adapt.

External to Internal Spiritual Authority

The Comfort of Tradition

Growing up in a conservative religious environment like Mormonism provided me with a sense of structure and security. The belief that a higher power controlled my life offered comfort, balancing grace with the responsibilities of devotion. Life’s biggest questions had answers, and the weight of uncertainty was lessened by the belief that someone else held the reins. In retrospect, I now understand this to be a natural stage of human development—that involves relying on external sources for guidance and safety.

A Shift in Spiritual Understanding

As I grew older, my need for external spiritual authority began to wane. My faith transition led me to question who Jesus was to me. While I still revere the historical figure and Christian values, my expectations of him as a Savior shifted. It felt as though Jesus “died,” not in the literal or traditional sense, but because he could no longer fulfill the role of an all-powerful figure who could rescue me from life’s difficulties. This was a jarring realization and a step toward understanding that the strength I sought resided within me, not in a figure outside myself.

Facing Life Without External Rescue

Without the comforting belief in an external divine rescuer, I’ve been forced to confront the consequences of my actions head-on. When I experience anxiety or sadness, there’s no longer a religious framework to hold me up or provide relief. Instead, I’ve learned to turn inward, tapping into my internal strength. This shift has been challenging, as it means taking full responsibility for my actions and their impact on others and myself. The loss of an external “reset” for human failures can be painful, yet it raises the question of whether such a resolution is truly necessary—or even possible.

Rediscovering Power Within

As a psychotherapist, I’ve found that the Internal Family Systems (IFS) model reflects much of this journey inward. IFS teaches that we all have a core “Self” capable of healing and loving the different parts of our psyche. It’s a concept that mirrors what traditional religions often attribute to an external divine force. In my spiritual journey, I’ve seen this internal power as immutable—something we all possess but may overlook if we remain focused on external sources. While these ideas can be unsettling for those who find comfort in traditional beliefs, I cannot return to my former way of thinking. Today, I believe that the Divine, if it exists, wants us to embrace our internal authority and stand firm in our power grounded in love and curiosity.

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If you find this topic interesting, I recommend Leaving the Saints: How I Lost the Mormons and Found My Faith, or The Dark Night of the Soul.

The Power of Psilocybin Therapy for Depression

Psychedelic-assisted psychotherapy is reshaping mental health treatments. A recent study investigating the effects of Psilocybin Therapy (PT) versus conventional antidepressants like Escitalopram (Lexapro) in treating Major Depressive Disorder (MDD) challenged traditional approaches. It highlighted the unique psychological mechanisms underpinning psychedelic therapy's success.

DALL-E, 2024

PT, utilizing psychoactive compounds found in magic mushrooms, induces deep, meaningful psychological experiences. These experiences, particularly mystical experiences and ego dissolution, play a key role in the treatment's effectiveness. Unlike traditional antidepressants focusing on serotonin levels for symptom management, PT leverages acute psychological transformations for long-term healing.

This study's trial with a rigorous control and double-blind structure compared PT against Escitalopram, a commonly prescribed Selective Serotonin Reuptake Inhibitor (SSRI). Patients undergoing PT reported significantly higher levels of mystical experiences and ego dissolution, linked to a greater reduction in depressive symptoms.

The study also highlighted the role of music during PT sessions in enhancing these experiences, suggesting the therapeutic setting significantly influences the treatment's efficacy. This aspect distinguishes PT from traditional treatments, pointing towards a holistic approach that integrates environment, mindset, and "drugs" to catalyze healing.

One striking finding was the durability of PT's effects. Patients treated with psilocybin showed lasting improvements, suggesting the acute psychological experiences induced by the therapy lead to long-term neuroplastic changes, contrasting with the maintenance approach of SSRIs, which often requires ongoing medication to manage symptoms.

What makes this exciting for me as a psychotherapist is the validation that the research expresses in reinforcing the significant aspect of impactful psychedelic psychotherapy as the mechanism of change in conjunction with rewiring the brain. These medicines themselves, in particular in microdose levels, do not necessarily create any more change than what you would see in classic psychiatric pharmacology.

This study validates the effectiveness of Psilocybin Therapy and highlights the role of mystical experiences and ego dissolution in driving therapeutic change. It paves the way for a new understanding of mental health treatment, where transformative psychological experiences are used for profound and enduring healing.

Reference:

Weiss, B., Roseman, L., Giribaldi, B., Nutt, D. J., Carhart-Harris, R. L., & Erritzoe, D. (2024). Unique Psychological Mechanisms Underlying Psilocybin Therapy Versus Escitalopram Treatment in the Treatment of Major Depressive Disorder. International Journal of Mental Health and Addiction, 1-36.