Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity.
Level 5 - mechanism / opinion, no new human data
Animal research with no human clinical data
PubMed 37000971 · doi:10.1097/CM9.0000000000002647
What was done
Mice underwent auditory cued fear conditioning followed by fear extinction training. Animals received a single intraperitoneal dose of psilocybin (2.5 mg/kg) or control 30 minutes before extinction training. Behavioral testing assessed percentage of freezing time during extinction testing (day 1 / 24 hours), extinction retrieval (day 6), and fear renewal (day 7). Biological assessments of hippocampal neuroplasticity included Golgi staining for dendritic complexity and spine density, Western blotting for BDNF and mTOR protein expression, and immunofluorescence for neurogenesis markers (DCX- and BrdU-positive cells in the dentate gyrus).
What was found
The abstract reports directional outcomes without exact numerical values, percentages, or confidence intervals. A single 2.5 mg/kg dose of psilocybin reduced the fear-conditioning-induced elevation in freezing time at 24 hours, day 6, and day 7. Psilocybin also reversed fear-conditioning-induced decreases in hippocampal dendritic complexity, spine density, BDNF protein levels, mTOR protein levels, and dentate gyrus DCX- and BrdU-positive cell counts.
Why it matters
The findings demonstrate a potential neurobiological mechanism—hippocampal structural plasticity and neurogenesis—through which psilocybin might enhance exposure-based fear extinction. This provides preclinical rationale for investigating psilocybin as an adjunct to exposure therapy in posttraumatic stress disorder.
Limits
The study was conducted exclusively in mice, so findings cannot be directly extrapolated to clinical human PTSD or exposure therapy protocols. The abstract does not provide sample sizes, effect sizes, variance measures, or dose-response comparisons, and it does not establish whether blocking neuroplasticity pathways directly abolishes psilocybin-facilitated fear extinction.
Cited by
- supports An animal study in mice showed that psilocybin administration increased neurogenesis in the dentate gyrus and facilitated fear extinction.