Double-Blind Trial: HBOT for Persistent Symptoms After Brain Injury
A double-blind trial gave 40 HBOT or sham sessions to adults with lasting symptoms after brain injury. The oxygen group improved on the primary measure, with caveats.
What was tested
A double-blind randomised trial published in Scientific Reports in February 2025 examined hyperbaric oxygen for adults who still had symptoms months to years after a non-stroke brain injury. Participants received either 40 hyperbaric oxygen sessions or 40 sham sessions over 12 weeks. Three months later, everyone was offered a further 40 unblinded oxygen sessions, which let the researchers watch the originally blinded groups over a longer horizon. Symptoms that persist months to years after a brain injury are notoriously hard to shift, which is part of what makes any controlled signal in this group worth examining.
The trial enrolled 49 participants and analysed 47 after drop-out and exclusions. Of those analysed, 26 were male and 40 had a traumatic brain injury; the remainder reflected other causes such as hypoxia or carbon monoxide exposure.
The primary result
The main outcome was a neurobehavioural symptom inventory scored at 13 weeks. The oxygen group improved by an average of about 10.6 points, compared with about 3.6 points in the sham group - a mean difference of 7.0 points (95 percent confidence interval 1.7 to 12.3; p = 0.01). That is a statistically significant separation in favour of oxygen on the primary measure.
A positive primary endpoint in a properly blinded trial is the kind of result that moves a question forward, because it is harder to explain away as expectation alone. The inventory used here is a standard self-report scale for neurobehavioural symptoms, so the improvement is one that patients themselves registered.
The nuance in the secondary results
The secondary outcomes are where the picture becomes more textured. Both groups - oxygen and sham - reported improvements in depression, headaches, PTSD symptoms, physical quality of life, and the degree to which their difficulties interfered with daily life. Improvements seen in both arms are a reminder of how strong sham responses can be in this setting, and of why an unblinded before-and-after look at HBOT can be so misleading.
The oxygen group additionally improved on measures of smell (olfaction), anxiety, sleep difficulties and vestibular complaints, and, after the extra unblinded sessions, reported further gains at 12 months. The authors present this as encouraging but not definitive, given the small sample and the mixed secondary picture.
How to weigh it
A well-conducted double-blind trial with a positive primary endpoint is meaningful, and blinding brain-injury patients to sham pressurisation is genuinely hard to do well. At the same time, 47 analysed participants is a small sample, and single trials rarely close a question on their own. Independent replication in larger and more diverse samples is the missing piece before firm clinical conclusions are drawn. For orientation on the sealed, single-occupant (monoplace) chambers used in studies like this, see our overview at monoplace chambers.
Persistent symptoms after a brain injury deserve a tailored medical plan. Use findings like these as a discussion point with a neurologist or rehabilitation physician, not as a reason to pursue treatment without medical oversight.