Psilocybin-associated microRNA changes in the pig brain: Establishing an nCounter pipeline for cross-species microRNA quantification.
Erik Kaadt, Rolf Søkilde, Hanne Demant Garling, N. Raval, Lene Lundgaard, Jesper Just, Gitte M. Knudsen, Betina Elfving
European Journal of Pharmacology August 1, 2026 DOI: 10.1016/j.ejphar.2026.179222 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Adolescent female pigs |
| Intervention | Psilocybin |
| Duration | 1 day and 7 days after a single dose |
| Topics | Psilocybin |
| Key findings | Psilocybin administration was associated with region- and time-dependent miRNA changes in pig brain: 12 dysregulated miRNAs in the prefrontal cortex and two in the hippocampus at 1 day, and four in the hippocampus at 7 days. Nine of 18 miRNAs had prior links to depression-related phenotypes; miR-212-3p and miR-107 showed the most robust acute regulation in the prefrontal cortex. |
Abstract
Novel treatment strategies are needed to address treatment resistance and delayed onset of action in psychiatry. Psilocybin has shown promise as a treatment for major depressive disorder, but the molecular changes associated with its effects remain incompletely understood. In parallel, microRNAs (miRNAs) have been implicated in depression and in responses to antidepressant interventions. Here, adolescent female pigs were used to explore miRNA expression profiles in the prefrontal cortex (PFC) and hippocampus (HIP) 1 day and 7 days after a single dose of psilocybin. We established a conservative NanoString nCounter workflow for pig tissue using the Human v3b miRNA Assay panel, cross-species reannotation based on complete human-pig sequence conservation, and evaluation of multiple normalization strategies. Using this pipeline, 12 dysregulated miRNAs were identified in the PFC and two in the HIP 1 day after psilocybin administration, whereas four dysregulated miRNAs were detected in the HIP after 7 days. Nine of the 18 miRNAs identified across the two regions have previously been linked to depression-related phenotypes. miR-212-3p and miR-107 showed the most robust acute regulation in the PFC across all four normalization approaches. These findings indicate that psilocybin administration is associated with region- and time-dependent miRNA changes in the pig brain and support the utility of this conservative nCounter pipeline for cross-species miRNA profiling. The study is exploratory and does not establish causality or direct antidepressant mechanisms.
Comparable studies
Other observational and cohort studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Patients with treatment-resistant depression | 2017 | Observational cohort | n = 19 |
| Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Healthy volunteers | 2019 | Observational cohort | n = 8 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Prediction of Psilocybin Response in Healthy Volunteers Healthy volunteers | 2012 | Observational cohort | n = 409 |
Citations in the library
Cites 18
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
and 13 more in the library