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A recent study conducted by Wolf and associates1 has stirred the waters, prompting a closer examination of its conclusions regarding Hyperbaric Oxygen Therapy (HBOT) for the treatment of mild traumatic brain injury (mTBI)/post-concussion syndrome (PCS) and post-traumatic stress disorder (PTSD). The study’s findings, when dissected, tell a more complex story than initially presented.

The Study in Question

The study under scrutiny involved 16 military subjects grappling with chronic blast-induced mTBI, PCS, and PTSD. These individuals underwent 40 sessions of HBOT at 2.4 atmospheres absolute (ATA) pressure over a period of 30 days. A battery of assessments, including symptom surveys, physical and neurological exams, neuropsychological testing, and Single Photon Emission Computed Tomography (SPECT) brain imaging, was administered both before and after treatment.

The Mischaracterization

The crux of the issue lies in how the study has been characterized. It was erroneously labeled as a sham-controlled study, implying a placebo effect. In reality, the study is a Phase II comparative dosing study examining two composite doses of hyperbaric therapy, not a sham-controlled trial. Both doses, one involving hyperbaric air and the other hyperbaric oxygen, yielded significant improvements in PCS and PTSD symptoms. This suggests that the study does not fit the definition of a true sham, which would omit the active ingredients of increased pressure and hyperoxia. The control group in the study, exposed to 1.3/1.2 ATA of air, indeed experienced increased pressure and oxygen levels, negating its classification as a true sham.

Notable enhancements in PCS and PTSD symptomatology were observed with both the 2.4 atmospheres absolute (ATA) pure oxygen dosage and the low-pressure 1.3 ATA air/oxygen regimen.

The Dual Nature of HBOT

HBOT is a multifaceted treatment modality. It combines increased pressure and elevated oxygen levels above ambient atmospheric pressure, making it a unique therapeutic approach. While it has historically been misconstrued as a treatment solely based on increased oxygen levels (>1.4 ATA oxygen), its true nature involves both pressure and hyperoxia. This dual-component approach targets oxygen and pressure-sensitive genes.

This understanding is grounded in a wealth of scientific literature spanning over 351 years of hyperbaric air therapy and 60 years of animal, human tissue, and human experiments. These studies have consistently demonstrated biological effects of pressure, particularly in the micropressure range, similar to the “sham” control group’s exposure in the study by Wolf and colleagues1. These effects include changes in vasoactive substances, growth factors, inflammatory mediators, and cell proliferation.

Unraveling the Effects

The study’s positive outcomes cannot be solely attributed to a placebo or other non-biological factors. Both the low-dose hyperbaric air and high-dose hyperbaric oxygen groups exhibited significant net improvements in PCS and PTSD symptoms. Notably, the pattern of change in composite ImPACT scores varied between the two groups, suggesting differential dosing effects and the possibility of an overdose response in the high-dose oxygen group.

This sinusoidal trajectory aligns with previous observations in other HBOT treatments for chronic cerebral disorders and underscores the need for a nuanced understanding of dosing in hyperbaric therapy. While Wolf and colleagues1 listed several possibilities for the improvements observed, including placebo effects and the Hawthorne effect, the differences in component and pattern changes in the ImPACT data and the transient overdose effect in the high-dose oxygen group remain unexplained by these non-biological factors.


The study by Wolf and colleagues demonstrated significant improvements in PCS and PTSD symptoms with both doses of hyperbaric therapy, showing promise when compared to existing therapies for these conditions.

Additionally, establishing an economical networked hyperbaric treatment program through a Coverage with Evidence Development pathway could expedite treatment for military and veteran casualties, avoiding unnecessary delays.


Harch, P. (2013, December 1). Hyperbaric Oxygen Therapy for Post-Concussion Syndrome: Contradictory Conclusions from a Study Mischaracterized as Sham-Controlled. National Library of Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837504