Psilocybin and DNA methylation changes in 37 people treated for alcohol use disorder

The question

Does a single dose of psilocybin change chemical marks on DNA (methylation) in people recovering from alcohol use disorder, and do any of those changes track with mood or drinking?

What they did

Researchers looked at blood samples from 37 detoxified patients with alcohol use disorder taking part in a randomized placebo-controlled trial. Participants received either 25 mg of psilocybin or a placebo (mannitol). Blood and questionnaire data were collected at the start, 24 hours after dosing, and one month later. The team scanned the whole genome for changes in DNA methylation, a chemical tag that can switch genes on or off without changing the DNA code itself.

What they found

The trial’s main goals (length of abstinence and average alcohol use) were not met. Among secondary measures, scores on the Beck Depression Inventory and the Beck Hopelessness Scale differed significantly between the groups. In the genome-wide scan, one site in the gene TLE4 was linked to psilocybin treatment (p = 1.1e-7), and a region in the gene RASGRP4 showed altered methylation (pFDR = 3.2e-4). Network analysis found clusters of co-changing sites tied to psilocybin, to reduced depressive symptoms and to drinking behaviour, with gene functions relating to brain plasticity and immune activity. At a weaker statistical threshold (p < 0.05), changes appeared near HTR2A (a serotonin receptor gene) and TNF (an inflammation gene).

The fine print

This was a small exploratory pilot: 37 people, blood-based methylation rather than brain tissue, and follow-up of only one month. The trial’s primary drinking outcomes were not achieved, so mood findings are secondary and could reflect chance or recovery from detox rather than psilocybin itself. Some gene results were only nominally significant, meaning they were not corrected for the large number of comparisons. This summary is based on the abstract alone.

What it means

The study offers early clues that psilocybin may be linked to shifts in gene regulation involving brain plasticity and immune pathways, but the sample was small and the trial did not improve drinking outcomes, so nothing here shows a clinical benefit.

Evidence grade: Low. Exploratory biomarker analysis inside a small randomized pilot trial (37 people) whose main drinking outcomes were not met, so the findings are preliminary and hypothesis-generating.

This summary is based on the study’s published abstract.