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

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.