Psychedelic drugs may help sustain PTSD recovery by triggering brain repair, according to new research in rats.
Psilocybin and MDMA can produce rapid effects in people with PTSD, but lasting benefits require brain circuits to stabilise.
The study suggests myelin, the insulating layer around nerve cells, may help bridge the gap between the short-lived psychedelic experience and longer-term recovery.
John Krystal, editor of Biological Psychiatry, said much of the focus in psychedelic and MDMA research has been on neurons and neuroplasticity, with less attention paid to other brain cell types that may also shape therapeutic effects.
Researchers used a rat model of contextual fear conditioning and gave repeated low doses of psilocybin or MDMA. They then measured anxiety-like and exploration behaviours and assessed spatial learning and memory.
The results showed that anxiety-like behaviours were reduced, alongside changes in oligodendrocyte biology and multi-omic, or genetic, signatures pointing to myelin remodelling in the dentate gyrus, part of the hippocampus involved in memory.
Mehmet Bostancıklıoğlu, of Gaziantep University faculty of medicine in Turkey, said the team combined the drug treatments with models that either damaged brain insulation or chemically enhanced it to test whether myelin integrity was simply linked to behavioural change or was actually required for it.
Using high-powered microscopy and genetic analysis, the researchers confirmed that both psilocybin and MDMA triggered physical myelin repair.
A 5-HT2A serotonin receptor blockade prevented both the behavioural and myelin-associated effects.
When the team used a different drug, anisomycin, to block the formation of fear memories, anxiety decreased but the myelin remained unrepaired, suggesting that while memories can be suppressed, biological recovery requires the structural support of myelin.
Krystal said: “The implication of oligodendrocytes in the therapeutic effects of psychedelics and MDMA is important because of their many functions in the brain, including myelin formation, glutamate homeostasis, and neuroinflammation.
The dependency of the therapeutic effects of these drugs in animals may suggest that myelin compromise may undermine their efficacy.
“Overall, these data suggest that psychedelics and MDMA, like selective serotonin reuptake inhibitors (SSRIs) and ketamine, may promote the recovery from stress-related damage to myelin, contributing to clinical recovery.”
The study also found that psilocybin and MDMA reduced astrocyte reactivity, which can cause inflammation.
The investigators said enhancing myelination would not be expected to replace psychotherapy, but could support the consolidation and maintenance of healthier network communication after the acute psychedelic session, when the brain is moving from destabilisation back towards reintegration.
Bostancıklıoğlu said: “We often talk about psychedelics as ‘opening a window’ for brain plasticity.
“Recent work emphasises that these drugs can acutely loosen entrenched network patterns and then leave a sub-acute period in which experience can reshape circuits.
“What we show here is that myelin-producing cells may be an underappreciated part of that story, helping translate a transient window into longer-lasting circuit change, at least in a fear-based rat model.”
