A single dose of psilocybin boosts neuroplasticity and reduces depression symptoms

A new study provides evidence that psilocybin, the active component in “magic” psychedelic mushrooms, induces lasting changes in neuroplasticity and that these changes are linked to improvements in depression symptoms. The research has been published in the Journal of Psychopharmacology.

Psilocybin, along with other psychedelics like LSD and DMT, has long been associated with vivid perceptual and mood alterations in humans. These effects are believed to be primarily mediated by the activation of serotonin 5-HT-2A receptors in the brain. However, while psychedelics have been used for centuries in various cultural and spiritual contexts, they fell out of favor in the mid-20th century due to legal restrictions and societal concerns.

But in recent years, researchers have reignited the interest in these substances, exploring their potential to treat a wide range of neuropsychiatric and behavioral health conditions. While traditional antidepressant medications can take weeks to produce noticeable improvements and need to be taken daily, early-phase trials suggested that psilocybin-assisted psychotherapy might offer rapid and long-lasting therapeutic effects after just one or two doses.

However, the mechanisms behind psilocybin’s therapeutic effects have remained largely elusive. To shed light on this, the researchers set out to investigate whether psilocybin therapy could enhance neuroplasticity – the brain’s ability to adapt and rewire itself. Understanding the mechanisms underlying the benefits of psilocybin could pave the way for more targeted and effective treatments for depression.

“If psychedelic treatments produce long lasting changes in mood after just one or two doses, characterizing the neural mechanisms underlying these enduring changes in the brain is important,” said study authors Deepak Cyril D’Souza (the Albert E. Kent Endowed Professor of Psychiatry at Yale University School of Medicine) and Patrick D. Skosnik (a professor at the Bouvé College of Health Sciences at Northeastern University).

The study involved 22 participants diagnosed with Major Depressive Disorder. These individuals had been living with depression for an average of 20 years and had previously undergone at least one unsuccessful antidepressant treatment. Importantly, they had been off conventional antidepressant medications for at least two weeks before enrolling in the study.

Participants underwent two dosing sessions about 4 weeks apart. In one session, they received a placebo (microcrystalline cellulose), and in the other, they received psilocybin (0.3 mg/kg, up to a maximum dose of 35 mg).

During each dosing session, participants were attended to by a study therapist and a psychiatrist. They were encouraged to have inward-directed experiences facilitated by supportive music and optional use of headphones and eyeshades. Psychoeducation and psychotherapy were provided before, during, and after dosing sessions.

The study included both clinical assessments and EEG (electroencephalography) measurements to evaluate the effects of psilocybin. The researchers specifically focused on a measure known as auditory evoked theta power, a particular pattern of electrical brain activity that has been linked to neuroplasticity. EEG data were collected 1 day and 2 weeks after each dosing session.

The researchers found that participants who received psilocybin experienced significant improvements in their depression symptoms. The effects were observed over time, with depression scores consistently decreasing in the weeks following psilocybin administration.

Two weeks after the administration of psilocybin, participants exhibited significantly increased auditory evoked theta power in their EEG readings. This suggests that psilocybin may enhance neuroplasticity in the brain, potentially contributing to its therapeutic effects.

“We found objective evidence using electroencephalography suggestive of enduring changes in the brain after exposure to just one dose of psilocybin,” D’Souza said.

“We were surprised that the brain changes after psilocybin (using our EEG measure of neuroplasticity) occurred only two weeks after psilocybin treatment,” Skosnik noted. “This suggests that some process/mechanism related to neural changes after psilocybin evolves days to weeks after treatment.”

Importantly, the researchers also examined the correlation between the change in depression scores and the change in theta power in the EEG data from 1 day to 2 weeks after psilocybin administration. A significant negative correlation was observed, indicating that as depression scores decreased (improved), theta power in the EEG increased.

As research in this field continues to evolve, the hope is that psychedelic such as psilocybin could offer new hope for individuals struggling with depression, offering rapid and sustained relief from their symptoms. However, further studies with larger cohorts and more diverse populations are needed to validate these preliminary findings and pave the way for safe and effective psychedelic-assisted therapies in the future.

“The findings must be replicated, as this was a relatively small study and sample size. Moreover, we need to try and understand the mechanisms underlying these changes,” the researchers said. “Lastly, we would like to thank the rest of our research team and coauthors, particularly Dr. Jordan Sloshower, who played a major role in bringing this study to fruition.”

The study, “Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms“, was authored by Patrick D. Skosnik, Jordan Sloshower, Hamideh Safi-Aghdam, Surbhi Pathania, Shariful Syed, Brian Pittman, and Deepak C D’Souza.

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