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

A pioneering trial combined microdoses of psilocybin with frontal-midline theta neurofeedback to improve executive functions in adults with deficits. Thirty-seven participants were randomly assigned to an experimental group (18 people) receiving three microdose sessions followed by three psilocybin-assisted neurofeedback sessions, or a passive control group (19 people). The approach proved feasible without psychological support. Neurofeedback learning showed a statistical trend with large effect size for increases in frontal-midline theta across sessions. No task-based improvements in executive functions emerged, but the experimental group reported significant gains in daily executive functions—working memory, shifting, monitoring, and inhibition—with medium to large effect sizes, and meaningful progress on self-selected training goals. The authors call for a larger study with an active control group to confirm specificity and lasting benefits.

Study at a glance

Abstract

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). 37 eligible participants were randomised into an experimental (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 with large effect size 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 EFs 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.