Patients with opioid use disorder treated with either methadone or buprenorphine are at risk of developing central sleep apnea (CSA) from these medications. Investigators will conduct a mechanistic trial using acetazolamide, a medicine known to improve CSA in other settings, to determine if acetazolamide can improve CSA due to medication for opioid use disorder and whether this leads to physiologic changes that might lead to reduced drug craving. Patients treated with medication for opioid use disorder and who have central sleep apnea will be randomized to treatment with acetazolamide or matching placebo for 7 days. At the end of the 7 days, they will undergo an overnight sleep study to assess the impact on breathing during sleep as well as sleep quality. In addition, measures of sympathetic tone, anxiety, arousal, cognition, and drug craving will be measured to determine if treatment of CSA with acetazolamide can produce physiologic changes that might contribute to improved health.

Medications used to treat opioid use disorder (MOUD) such as methadone and buprenorphine have been found to cause central sleep apnea (CSA), but the clinical ramifications are unclear. It has been hypothesized that the sleep fragmentation and intermittent hypoxemia caused by CSA from MOUD may lead to sympathetic activation, nocturnal arousal, increased anxiety, and cognitive impairment that may in turn increase drug craving and drug relapse. This mechanistic study will evaluate the potential adverse effect of CSA in patients on MOUD by evaluating the impact of acetazolamide to improve CSA and thereby lead to downstream physiologic changes in measures of sleep quality, sympathetic tone, nocturnal arousal, anxiety, cognitive functioning, and drug craving.

Eligible individuals will undergo an overnight research visit including overnight polysomnography, assessments of autonomic tone, sleep quality, nocturnal arousal, emotional distress, cognitive testing, and drug craving. Individuals with opioid-induced CSA will be randomized into a parallel-arm trial of acetazolamide vs. placebo with overnight research visit for outcome assessment at 7 days.

Inclusion Criteria:

• Patients on Medication for Opioid Use Disorder (MOUD) with central sleep apnea.

Exclusion Criteria:

• Sleep-related Hypoventilation.
• Other causes of Central Sleep Apnea besides Opioid Use.
• Pregnancy.
• Contraindications for Acetazolamide.

Individual Participant Data (IPD) from this clinical trial will be shared with other researchers. The IPD to be shared includes final closed dataset (after de-identification). All data will be released according to the specific timelines stated in the National Institutes of Health (NIH) Policy, ensuring no compromise to privacy, confidentiality, proprietary interests, national security, or law enforcement activities. These data will be submitted to a NIH-funded data registry for data sharing purposes.

The IPD will become available within 1 year of analysis of primary outcome. This data will be accessible on an NIH-sponsored platform for as long as the agency maintains it.

IPD will be available through a NIH funded registry. Access to the IPD will be governed by the policies and procedures of NIH.

Placebo pill matched to look like active drug.