MDMA and psilocybin regulate oligodendrocyte-lineage cell numbers and anxiety-like behaviors in a rat model of fear.
Biological psychiatry February 3, 2026 Mehmet Bostancıklıoğlu, Davut Sinan Kaplan, Ramazan Bal et al.
Psilocybin and MDMA reduce anxiety-like behaviors in a rat model of fear conditioning, and these effects depend on myelin plasticity in the dentate gyrus. Both drugs triggered oligodendroglial changes and multi-omic signatures of myelin remodeling, though mean myelin thickness (g-ratio) did not differ significantly between treated and untreated fear-conditioned animals. Disrupting myelin abolished the anxiolytic effects. Psilocybin preferentially activated early oligodendroglial gene programs, while MDMA enhanced markers of mature myelin. Blocking the 5-HT2A receptor completely eliminated both the myelin and behavioral enhancements. Enhancing myelination may be a viable strategy to sustain therapeutic effects of psychedelic-assisted treatments for PTSD.