Widespread executive function deficits impair daily functioning in psychiatric disorders. In this group, reduced frontal-midline-theta neurofeedback responsiveness may be related to impaired neural plasticity. In our pioneering study, we investigated the feasibility and practicality of integrating a neuroplasticity agent by psilocybin-assisted neurofeedback. Thirty-seven participants were divided into an experimental and a passive control group. The experimental group received three microdose sessions followed by three psilocybin-assisted neurofeedback sessions. Our results showed changes in self-regulatory frontal-midline theta from session-to-session approaching significance. Importantly, placebo ratings and expectations did not differ between the two groups. There were no immediate improvements in the experimental tasks assessing executive functions. However significant improvements were observed in self-reported executive functions in daily life. Participants reported improvements in working memory, shifting, monitoring and inhibition with high effect sizes. In addition, the experimental group reported positive changes in their priority areas, which included cognition, presence and mood. These results suggest that psilocybin-assisted neurofeedback shows promise for a potential transdiagnostic treatment. Future research should investigate the optimal timing and duration of this pharmacological and neuroscientific combination. Overall, our study highlights the feasibility and potential of this innovative approach, emphasizing the potential for enhanced neuroplasticity that may amplify the impact of neurofeedback.