The Scale of Off-Label HBOT Use
Of 9,726 HBOT registry entries analyzed in a 2023 multicenter study, 45 conditions being treated fell outside FDA-cleared indications. Long COVID, ulcerative colitis, and post-concussion syndrome were the most common off-label uses. The gap between what clinicians treat and what insurance covers is growing, and a $28 million clinical trial at USF is now enrolling 400+ veterans to help close it.
“Off-label” means using an FDA-cleared device for a condition not on the cleared list. This is legal and common across medicine. For HBOT, the off-label share is particularly high in freestanding clinics and home chamber users.
Top Off-Label Conditions: Registry Data
From the International Multicenter Registry for Hyperbaric Oxygen Therapy (Tanaka et al. 2023):1
| Condition | Patients | % of Off-Label Cases | Key Outcome |
|---|---|---|---|
| Post-COVID (Long COVID) | 149 | 39.4% | NSI score: 30.6 pre to 14.4 post (P<0.001) |
| Ulcerative colitis | 47 | 12.4% | Improved QOL (EQ-5D), lower bowel scores |
| Crohn’s disease | 40 | 10.6% | EQ-5D: 53.8 to 68.8; 13% fistula closure |
| Calciphylaxis | 20 | 5.3% | Subset reported improvement |
| Frostbite | 18 | 4.8% | Case-level improvements |
“A multicenter registry study identified 45 emerging conditions being treated with HBOT outside approved indications. Long COVID, ulcerative colitis, and Crohn’s disease accounted for over 62% of off-label cases.”
Tanaka et al. 2023, Interactive Journal of Medical Research
Off-Label Conditions by Evidence Level
| Evidence Level | Conditions | Study Type |
|---|---|---|
| Strong emerging (RCTs) | Long COVID, IBD (Crohn’s, UC) | Randomized controlled trials |
| Moderate (cohort/case studies) | TBI, calciphylaxis, frostbite, fertility | Phase I/II trials, prospective studies |
| Weak (anecdotal) | Anti-aging, athletic recovery, Lyme disease, autism | Case reports, anecdotes |
| No evidence / FDA-warned | Cancer, Alzheimer’s, Parkinson’s, ADHD | Do not recommend |
Long COVID: The Leading Off-Label Use
Long COVID is the most common emerging indication in registry data, accounting for 39.4% of all off-label HBOT cases.1 NSI scores improved from 30.6 to 14.4 (P<0.001) in the registry cohort. The Tel Aviv RCT (Zilberman-Itskovich et al. 2022) demonstrated significant improvements in cognitive function, energy levels, and brain perfusion on MRI in 73 post-COVID patients.5
TBI: The $28 Million Trial
Traumatic brain injury is one of the most active areas of off-label HBOT research. A landmark $28 million clinical trial at the University of South Florida is currently enrolling 400+ veterans to evaluate HBOT for TBI and PTSD using a gold-standard RCT design.7
“A landmark $28 million clinical trial at USF is currently enrolling 400+ veterans to determine whether HBOT can effectively treat traumatic brain injury and PTSD.”
USF Health 2025
The FDA Position
The FDA has explicitly warned consumers that HBOT has not been clinically proven to treat cancer, autism, diabetes, Alzheimer’s, or Parkinson’s disease.2 Off-label use by licensed practitioners is legal but should be based on clinical judgment and informed patient consent.
What Do Clinical Studies Show?
As of 2026, approximately 200+ active clinical trials involving HBOT are registered on ClinicalTrials.gov. The most-studied off-label conditions in active trials include:
- Long COVID / post-COVID condition (20+ active trials)
- TBI and concussion (15+ active trials)
- Cognitive decline and dementia (10+ active trials)
- Psychiatric conditions including depression and PTSD (8+ active trials)
- Autoimmune conditions (5+ active trials)
Utilization by Setting
- Hospital wound care centers: Less than 5% off-label (insurance-driven, limited to cleared indications)
- Freestanding HBOT clinics: 30-50% off-label (mix of on-label and cash-pay off-label)
- Integrative/functional medicine: 80-100% off-label
- Home chambers: ~100% off-label
- Tanaka H, Rees JR, Zhang Z et al. (2023). Emerging indications for hyperbaric oxygen treatment: Registry cohort study. Interactive Journal of Medical Research. DOI: 10.2196/53821. PMID: 39078624.
- FDA Consumer Update. Hyperbaric oxygen therapy: Get the facts. fda.gov/consumers/consumer-updates/hyperbaric-oxygen-therapy-get-facts
- UHMS. Hyperbaric Oxygen Therapy Indications, 14th Edition. 2024. uhms.org
- Harvard Health. (2024). Hyperbaric oxygen therapy: Evidence-based uses and unproven claims. health.harvard.edu
- Zilberman-Itskovich S et al. (2022). HBOT improves neurocognitive functions and symptoms of post-COVID condition. Scientific Reports. 12:11252. DOI: 10.1038/s41598-022-15565-0
- Dokmak A et al. (2023). Efficacy and safety of HBOT in fistulizing Crohn’s disease. Inflammatory Bowel Diseases. DOI: 10.1093/ibd/izac247.121
- USF Health. (2025). Veterans powering landmark hyperbaric oxygen research. usf.edu
- ClinicalTrials.gov. Active HBOT clinical trials. clinicaltrials.gov
- HBOT USA. (2026). Why so much HBOT use is off-label (and what that actually means). hbotusa.com
- Efrati S et al. (2020). HBOT increases telomere length and decreases immunosenescence. Aging. DOI: 10.18632/aging.202188
Medical Disclaimer
The content on BaricBoost.com is for informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Author
Seph Fontane Pennock is the founder of BaricBoost.com and Regenerated.com, a clinic directory for regenerative medicine serving 10,000+ providers across the United States. He previously built and sold PositivePsychology.com, which grew to 19 million users and became the largest evidence-based positive psychology resource on the web. Seph brings direct experience as an HBOT patient, having completed protocols at clinics across three continents while navigating mold illness, systemic inflammation, and autoimmune conditions. His treatment journey includes hyperbaric oxygen therapy, peptide protocols, NAD+ therapy, and consultations with specialists from Dubai to Cape Town to Mexico. This combination of entrepreneurial track record and lived patient experience shapes everything published on BaricBoost.com. Every article is grounded in peer-reviewed research, informed by real clinical encounters, and written for patients making high-stakes treatment decisions. Seph's focus is on bringing transparency, scientific rigor, and practical guidance to the hyperbaric oxygen therapy space.
