A study published in Nature Communications reveals that a single dose of psilocybin, the active compound in magic mushrooms, may induce lasting structural changes in the brain, including increased entropy, with effects measurable a month later, according to research led by UCSF and Imperial College London.
The research, involving 28 healthy adults with no prior psychedelic use, found that a 25-mg psilocybin dose triggered temporary increases in brain entropy—measured via EEG—linked to heightened psychological insight and improved well-being. Psychedelic means 'psyche-revealing,' or making the psyche visible,
said senior author Robin Carhart-Harris, PhD, professor of neurology at UCSF, emphasizing that the “trip” itself may be critical to therapeutic benefits.
Brain Entropy and Lasting Structural Changes
Psilocybin’s effects on brain entropy were observed within 60 minutes of a 25-mg dose, with participants exhibiting more diverse neural activity. This entropic state correlated with greater psychological insight the following day and improved well-being a month later. Researchers used diffusion tensor imaging (DTI) to track changes in neural tracts, finding decreases in axial diffusivity within prefrontal-subcortical white matter tracts—a pattern researchers noted was the reverse of changes commonly associated with aging, when neural tracts tend to become more diffuse. Of an array of findings, decreases in the diffusivity of large tracts running between the prefrontal cortex and the center of the brain are perhaps the most intriguing,
Carhart-Harris noted.
Participant Experiences and Cognitive Gains
All but one participant described the 25-mg psilocybin session as the single most
unusual state of consciousness they had ever experienced. The remaining participant ranked it among the five most unusual experiences of their life. Psychological insight scores rose significantly post-dose. Measures of well-being, including responses to statements such as I've been feeling optimistic about the future
and I've been dealing with problems well,
improved two and four weeks after the dose. Cognitive flexibility, assessed via standardized tests, also showed gains a month later.
These findings align with earlier clinical trials suggesting psilocybin’s potential for treating treatment-resistant depression, cancer-related anxiety, and alcohol use disorder. However, the study’s focus on healthy volunteers rather than patients with psychiatric conditions limits direct applicability. The weight of the human evidence suggests that the trip experience is critical for therapeutic benefits,
Carhart-Harris said.
Expert Analysis and Unanswered Questions
Experts like Alex Kwan, PhD, professor at the Meinig School of Biomedical Engineering, Cornell University, highlighted the study’s significance in linking psilocybin to structural brain changes. This study moves the needle by providing evidence for persistent structural brain changes following psilocybin use,
Kwan said, though he cautioned the sample size was small and the findings preliminary. We don’t yet know what the functional implications of these changes are,
Carhart-Harris added, stressing the need for follow-up research.
The study’s design—administering a 1-mg placebo dose first, then a 25-mg dose—raised questions about practice effects or expectations. Researchers noted that while the results are promising, they require replication. We’ve not yet had any success in this regard but, with the executive order, are now hopeful of change,
Carhart-Harris said, referencing recent federal efforts to expand psychedelic research.
Implications for Psychedelic Therapy
The findings add to a growing body of evidence supporting psychedelics as tools for mental health treatment. By demonstrating that psilocybin can alter brain structure and function in healthy individuals, the study suggests potential applications for conditions involving rigid thought patterns. However, the lack of patient data and the exploratory nature of the research mean clinical applications remain speculative.
As federal policies shift to permit more research, scientists like Carhart-Harris and Lyons hope to explore how these brain changes might be harnessed therapeutically. The fact that these changes track with insight and improved well-being is especially exciting,
Lyons said. For now, the study underscores the complex interplay between psychedelic experiences, neural plasticity, and psychological healing.
