Psilocybin-assisted neurofeedback for the improvement of executive functions: a randomized semi-naturalistic-lab feasibility study

This preprint randomised feasibility study (n=37) evaluates psilocybin-assisted (microdoses x 6) frontal-midline theta neurofeedback (NF) to improve executive functions (EFs) in participants with psychiatric disorders. Despite no significant improvements in tasks-based EFs, the experimental group reported medium to high gains in daily EFs, indicating the potential benefits of this neuromodulation technique for enhancing daily functioning.

Abstract of Psilocybin-assisted neurofeedback for the improvement of executive functions

Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique leveraging neuroplasticity, to improve executive functions (EFs). Thirty-seven eligible participants were randomized into an experimental group (n = 18) and a passive control group (n = 19). The experimental group underwent three microdose sessions and then three psilocybin-assisted NF sessions, without requiring psychological support, demonstrating the approach’s feasibility. NF learning showed a statistical trend for increases in frontal-midline theta from session to session with a large effect size and non-significant but medium effect size dynamical changes within sessions. Placebo effects were consistent across groups, with no tasks-based EF improvements, but significant self-reported gains in daily EFs—working memory, shifting, monitoring and inhibition—showing medium and high effect sizes. The experimental group’s significant gains in their key training goals underscored the approach’s external relevance. A thorough study with regular sessions and an active control group is crucial to evaluate EFs improvement and their specificity in future. Psilocybin-enhanced NF could offer significant, lasting benefits across diagnoses, improving daily functioning.

Authors: Stefanie Enriquez-Geppert, Jaroslav Krc, Fiachra J. O’Higgins, Morten Lietz

Summary of Abstract of Psilocybin-assisted neurofeedback for the improvement of executive functions

Executive function deficits are widespread across psychiatric disorders and significantly impact daily functioning. These deficits, which affect abilities like planning, decision-making, and self-control, are linked to reduced neural plasticity – the brain’s ability to form new connections and adapt. This reduced plasticity can make both behavioural and medication-based treatments less effective. With global mental health challenges increasing, there is an urgent need for more accessible and effective interventions that specifically target cognitive enhancement.

The neural basis of executive functions involves a network connecting the frontal and parietal regions of the brain, with a particular type of brain activity called frontal-midline theta serving as the communication mechanism. This theta activity, primarily generated in the midcingulate cortex and dorsolateral prefrontal cortex, is strongly associated with improved cognitive processing. When people struggle to increase this theta activity, their performance on executive function tasks typically suffers.

Recent research has shown that psychedelics, particularly psilocybin, can create rapid and lasting clinical benefits even after few doses. Their ability to enhance neuroplasticity through specific receptor interactions makes them potentially valuable tools for cognitive enhancement. However, their powerful hallucinogenic effects typically require controlled environments. Microdosing – taking sub-threshold doses about 1/10th to 1/20th of a therapeutic dose – may offer a more practical approach while still promoting neuroplasticity.

Methods

Recruitment and Study Design

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Psilocybin-assisted neurofeedback for the improvement of executive functions: a randomized semi-naturalistic-lab feasibility study

https://doi.org/10.1098/rstb.2023.0095

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Cite this paper (APA)

Enriquez-Geppert, S., Krc, J., O'Higgins, F. J., & Lietz, M. (2024). Psilocybin-assisted neurofeedback for the improvement of executive functions: A randomized semi-naturalistic-lab feasibility study. Philosophical Transactions of the Royal Society B, 379(20230095). https://doi.org/10.1098/rstb.2023.0095

Study details

Compounds studied
Psilocybin

Topics studied
Microdosing Neuroscience

Study characteristics
Open-Label Randomized Theory Building Bio/Neuro

Participants
37 Humans

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