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Common Diuretic Pill Cuts Opioid-Linked Breathing Pauses In Small Trial

People on long-term opioids often develop broken, pause-filled breathing at night, and this trial tested a drug that may calm it.

A drug called acetazolamide reduced opioid-related sleep-disordered breathing by 22% compared with a placebo pill, according to a study published August 28, 2026 in the Journal of Applied Physiology.

9-personcrossover trial
22%fewer breathing pauses
82%fewer central apneas
6-daytreatment period

Nine adults with opioid-associated sleep-disordered breathing, a condition where chronic opioid use slows and destabilizes breathing during sleep, took oral acetazolamide or a placebo pill for 6 days each in a crossover design, with order randomized. On day 4 of each period researchers measured breathing responses to added carbon dioxide while awake, then breathing-control signals during non-REM sleep using a breathing machine, followed by an overnight sleep study. Blood tests confirmed opioid and acetazolamide use in each period. Compared with placebo, acetazolamide reduced overall breathing-pause severity from 32.2 to 25.2 pauses per hour, a 22% drop, and cut central breathing pauses from 5.0 to 0.9 per hour, an 82% drop, with higher oxygen saturation overnight.

The authors attributed this to a fall in plant gain, the sensitivity of the lungs and blood vessels to carbon dioxide changes, from 6.6 to 4.0 mmHg per liter per minute, driven by acetazolamide-induced mild metabolic acidosis. That acidosis raised resting breathing rate from 6.8 to 10.0 liters per minute and lowered resting carbon dioxide from 41.6 to 33.1 mmHg. A separate control measure, controller gain, and the brain's blood vessel response to carbon dioxide did not change.

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The trial enrolled only 9 people for 6 days per period. The abstract did not report conflicts, side effects or discontinuations for either period.

Opioids blunt the brain's drive to breathe and make the breathing-control system overreact to small carbon dioxide shifts, producing the pauses and oxygen dips seen in this condition. The authors' finding suggests a drug that nudges blood chemistry toward mild acidity can steady that overreaction without changing the opioid dose itself.

Acetazolamide cut central breathing pauses 82% vs placebo

Acetazolamide cut central breathing pauses 82% vs placebo9 adults, crossover trial, 6 days per treatment. Placebo: 5 pauses/hour; Acetazolamide: 0.9 pauses/hour9 adults, crossover trial, 6 days per treatment
5 pauses/hour
PLACEBO
0.9 pauses/hour
ACETAZOLAMIDE
Journal of Applied Physiology, 2026, Greig et al.

Nine adults tracked for 6 days per period is too small and short to show whether the drug changes long-term outcomes like heart health or daytime symptoms.

Dr. Axe’s Take

The mechanism here makes sense even in a 9-person trial: opioids blunt the brain's steady breathing signal and make it overcorrect when carbon dioxide swings, and a drug that shifts blood chemistry slightly acidic appears to settle that overreaction. But this is a second drug added to manage a side effect of the first, and it works by deliberately changing your blood chemistry. For anyone on long-term opioids, the bigger question is the root cause: working with a physician on pain management and whether the opioid dose can safely come down over time. If you or someone you love is on long-term opioids and has loud snoring, witnessed breathing pauses or morning headaches, get a sleep study, and don't change any prescribed medication on your own. Alongside that, sleeping on your side, avoiding alcohol near bedtime and keeping nasal passages clear still support steadier breathing overnight.

Dr. Axe— Dr. Axe

Study summary

Who
9 adults with opioid-associated sleep-disordered breathing
Design
Randomized, crossover trial comparing oral acetazolamide with placebo, each for 6 days, with measurements on day 4 and an overnight sleep study
Dose
Oral acetazolamide for 6 days per period versus placebo for 6 days per period, order randomized
Primary result
Apnea-hypopnea index (overall breathing pauses per hour) fell from 32.2 to 25.2 per hour, a 22% reduction; central apnea-hypopnea index fell from 5.0 to 0.9 per hour, an 82% reduction
Secondary
Plant gain fell from 6.6 to 4.0 mmHg/L/min; resting minute ventilation rose from 6.8 to 10.0 L/min; resting end-tidal CO2 fell from 41.6 to 33.1 mmHg; controller gain and cerebrovascular CO2 responsiveness were unchanged
Funding / conflicts
Funder listed in the journal record: U.S. Department of Veterans Affairs. Conflicts not reported in the abstract.
Date
Aug 28, 2026
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