Raymond M. Quock

Opioids are a leading cause of drug overdose deaths in the United States. Methadone used as medication for opioid use disorder (MOUD) reduces drug cravings and promotes abstinence. However, individuals in methadone-based MOUD treatment commonly report subjective sleep complaints and are at risk for respiratory depression from opioids. We investigated nighttime sleep and respiratory function in eight individuals (six women, two men; ages 31–68 years) in their first 90 days of methadone-based MOUD treatment. Participants underwent overnight cardiorespiratory polysomnography. Sleep and respiratory variables were characterized with descriptive statistics for comparison to reference data from similarly aged healthy adults. Although participants spent 8.1 ± 0.3 hours (mean ± SD) in bed, their total sleep time was only 6.8 ± 1.3 hours. They exhibited longer sleep latency and intermittent wakefulness. Sleep structure was irregular, with disrupted sleep cycles. Participants also displayed a decreased amount of N1 sleep and an increased amount of N3 sleep, compared with reference data. Participants showed respiratory depression, with an average apnea–hypopnea index of 16.5 ± 8.9 events per hour. Central sleep apneas comprised 69.1% ± 20.9% of the respiratory events. A Cheyne–Stokes-like breathing pattern, consisting of 30-second cycles of three central sleep apneas, was observed in 75% of participants. Our results suggest that individuals early in methadone-based MOUD treatment experience disordered sleep and respiratory disturbances. Such nighttime physiological changes may have serious long-term health consequences and contribute to unintended overdose rates. Identifying and treating MOUD individuals with sleep apnea could reduce risk of death.

Opioid withdrawal symptoms can interfere with substance use disorder treatment goals. This study investigated the acceptability, feasibility, and treatment effects of hyperbaric oxygen therapy (HBOT) as an adjunct to reduce withdrawal symptoms for adults initiating a medically supervised methadone dose reduction. Adults prescribed methadone for opioid use disorder were randomized into either a hyperbaric oxygen group (n = 17) or an attention control group (n = 14). The study site was an outpatient opioid treatment program in the northwestern United States. Participants were asked to attend five consecutive daily 90-minute HBOT sessions offered at 2.0 atmospheres absolute with 100% oxygen in a pressurized chamber. Treatment attendance and reported satisfaction were measures of acceptability and feasibility. Medication doses were tracked posttreatment at 1 week, 1 month, and 3 months. Withdrawal symptoms were assessed at baseline and daily during the 5-day intervention period. After randomization, 13 (76.5%) followed through with medical screening and HBOT sessions, and of those, nine (69.2%) completed all five 90-minute HBOT sessions. At 3 months, the treatment group maintained, on average, a 4.3-mg methadone dose reduction compared with an average reduction of 0.25 mg for control group participants. Opioid withdrawal symptoms were reduced after Day 1 of HBOT by twice as much, on average, compared with the control condition. Satisfaction surveys found participants were generally satisfied with ease and comfort of the treatment. The evidence that HBOT is an acceptable, feasible adjunct warrants future trials to determine more conclusively effects on withdrawal symptoms associated with methadone dose taper.

Background: Previous research from our laboratory implicated opioid and benzodiazepine- GABA mechanisms in other effects of N2O (antinociception and anxiolysis), so a decision was made to study these as potential mechanisms of N2O-induced dysfunction of spatial working memory. Objective: to explore potential mechanisms of N2O in reducing spatial working memory in mice. Methods: we monitored spontaneous alternation behavior (SAB) in male NIH Swiss mice exposed to N2O during a T-maze spontaneous alternation task (T-SAT). Results: mice that were exposed to 70% N2O (in O2) exhibited severely and significantly reduced spontaneous alternation behavior in the T-SAT. Mice in this environment alternated their route only 33% of the time, in comparison to the control (room air) rate of alternation at approximately 70%. Mice pretreated with the benzodiazepine antagonist, flumazenil exhibited a dose-dependent restoration of spatial working memory under 70% N2O in the T-SAT. Alternatively, pretreatment with neither the GABAA antagonist gabazine nor the opioid antagonist naloxone had any appreciable effect on the N2O-reduced SAB. Conclusion: this study verified that 70% N2O can reduce spatial working memory in mice, which appears to involve benzodiazepine mechanisms in the brain.

Background: Hyperbaric oxygen (HBO₂) therapy can produce analgesia in patients experiencing various conditions of chronic pain. Previously, we reported that naloxone antagonized the acute antinociceptive effect of both brief (11 min) and longer (60 min)HBO₂treatments. This implied a possible role for opioid receptors in the antinociceptive effects ofHBO₂.Objectives: The aim of this study was to determine whether mice previously rendered as tolerant to opioid agonists would exhibit a reduced antinociceptive responsiveness toHBO₂.Methods: MaleNIH Swiss mice were given repeated injections of the opioid agonists morphine, fentanyl or (‐)‐U50488Hover 4 days to induce tolerance at their respective opioid receptors. Mice receiving saline according to a similar injection schedule served as a vehicle control group. On day 5, 15 h after the last injection, mice received either an antinociceptive challenge dose of the opioid agonists or a 30‐minHBO₂exposure at 3.5 atmosphere absolute. The antinociception was then assessed by the 0.6% acetic acid‐induced abdominal constriction test.Results: The results showed that mice rendered as tolerant to morphine, fentanyl or (‐)‐U50488Hpretreatment all exhibited reduced antinociceptive responsiveness to themselves andHBO₂.Conclusions: These results demonstrated that both μ‐ and κ‐opioid receptors are involved in mediation of the acute antinociceptive response toHBO₂.