Psilocybin mitigates chronic behavioral and neurobiological alterations in a rat model of recurrent intimate partner violence-related brain injury
Psilocybin could help reverse brain damage from domestic violence related injuries, a new rodent study suggests.
A new Rodent Study suggests psilocybin could help reverse brain damage from domestic violence related injuries. Intimate partner violence (IPV) poses a significant medical concern, predominantly affecting females. IPV-related brain injuries (IPV-BI), such as mild traumatic brain injury (mTBI) and non-fatal strangulation (NFS), sustained during physical attacks are common and often repetitive.
Chronic neurobehavioral sequalae from IPV-BI are associated with neuroinflammation and impaired neuroplasticity, and effective treatment options are scarce, particularly in the context of IPV. However, psilocybin, a 5-HT2A receptor agonist with therapeutic potential in psychiatric disorders that share overlapping pathophysiology as BI, is a promising candidate. This study evaluated psilocybin's effects on behavior, cognition, and neurobiology in a novel rat model of recurrent IPV-BI. Female rats underwent daily mTBI (lateral impact) followed by NFS (90 s) for five days, followed by 16 weeks of recovery. Rats then received a single intraperitoneal injection of psilocybin (1 mg/kg) or saline, with behavioral testing 24 h later.
To investigate whether psilocybin's effects were 5-HT2A receptor dependent, additional rats received pre-treatment with selective 5-HT2A receptor antagonist M100907 (1.5 mg/kg) one hour before psilocybin administration. Psilocybin recovered mTBI+NFS-induced abnormalities in the elevated plus-maze, increased sucrose preference when administered without M100907, and improved reversal learning in the water maze and spatial memory in the Y-maze. In the dorsal hippocampus, mTBI+NFS rats treated with saline, but not those treated with psilocybin, exhibited an increased number of microglial cells in the molecular layer and fewer reelin-positive cells in the subgranular zone.
These findings suggest psilocybin's antidepressant, pro-cognitive, anti-inflammatory, and neuroplasticity-enhancing effects hold promise for improving chronic IPV-BI outcomes and highlight the critical role of 5-HT2A receptors in mediating psilocybin's therapeutic benefits.
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The results suggest psilocybin has multiple beneficial effects: anti-inflammatory, pro-cognitive, antidepressant/anxiolytic, and neuroplasticity-enhancing — at least in this animal model. That raises the possibility that it might help in humans suffering chronic brain injury after repeated trauma (e.g. IPV, repeated head impacts).The article argues that crucial, non-pharmacological factors are being marginalized by the push for standardization.
The dependency on the 5-HT₂A receptor supports the hypothesis that psilocybin’s beneficial effects in trauma/injury contexts overlap with those in psychiatric conditions — via receptor-mediated modulation of neuroplasticity and inflammation.
It is important to note this is an animal study. As such, the extent to which findings translate to human survivors of IPV or repeated brain trauma is uncertain. The authors note that effective treatment options are scarce in the IPV context — but also that more research (especially clinical trials) would be required
This study is among the first to:
Use a realistic and clinically relevant animal model of repeated brain injuries from trauma (mTBI + NFS) — approximating conditions faced by some survivors of intimate partner violence.
Show that a single dose of psilocybin can reverse long-term behavioural, cognitive, and neurobiological damage long after injury, pointing to neuroinflammation and impaired neuroplasticity as mechanisms — and 5-HT₂A receptor activation as central mediator.
Provide a proof of principle for psychedelics (specifically psilocybin) as potential therapeutic agents for chronic brain injury from trauma — a domain with very limited treatment options until now.
Allen J, Sun M, Baker TL, Dames S, Kryskow P, Christie BR, McDonald SJ, Shultz SR. Psilocybin mitigates chronic behavioral and neurobiological alterations in a rat model of recurrent intimate partner violence-related brain injury. Mol Psychiatry. 2025 Nov 5. doi: 10.1038/s41380-025-03329-x. Epub ahead of print. PMID: 41193674. View Paper
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