Psilocybin, neuroplasticity and the default mode network in anti-aging research

In an All-In Podcast, longevity entrepreneur Bryan Johnson said psychedelics may become rejuvenation protocols for anti-aging. He highlighted psilocybin research as potentially longevity-relevant, pointing to preclinical mouse evidence and linking psilocybin’s effects to changes in the brain’s default mode network (DMN). Johnson argued that aging stiffens DMN patterns, narrowing how people perceive reality; psilocybin may dampen DMN activity and reshape self/ego perception. He also described how psilocybin could drive neuroplasticity by “scrambling” neural activity patterns, potentially rewiring repeated trauma/anxiety circuitry. Johnson further discussed Five MEO DMT as strongly suppressing the DMN, producing “childlike” excitement and clarity. The conversation stressed scientific and safety challenges. Johnson said brain rejuvenation is harder than improving organs like the heart and lungs. He cited extensive, measured ketamine therapy work for depression (before/during/after) as an example of rigorous data collection. While Johnson sees psychedelic compounds as promising for longevity, he warned that risks often come from unregulated, unsupervised use—such as people not knowing mushroom strain or operating in the wrong “set and setting.” He called for licensed professionals and a safety structure to reduce harm. Main themes: psilocybin for anti-aging, DMN modulation, neuroplasticity, and the push for controlled, evidence-based psychedelic medicine.