Nighttime Sleep and Respiratory Disturbances in Individuals Receiving Methadone to Treat Opioid Use Disorder.

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.

Co-consuming green tea with raloxifene decreases raloxifene systemic exposure in healthy adult participants.

Green tea is a popular beverage worldwide. The abundant green tea catechin (-)-epigallocatechin gallate (EGCG) is a potent in vitro inhibitor of intestinal UDP-glucuronosyltransferase (UGT) activity (K  ~2 μM). Co-consuming green tea with intestinal UGT drug substrates, including raloxifene, could increase systemic drug exposure.

Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom.

Oral formulations prepared from the leaves of the kratom (Mitragyna speciosa) plant are increasingly used for their opioid-like effects to self-manage opioid withdrawal and pain. Calls to US poison centers involving kratom exposures increased >50-fold from 2011-2017, one-third of which reported concomitant use of kratom with drugs of abuse. Many of these drugs are eliminated primarily via cytochrome P450 (CYP) 3A and CYP2D6, raising concerns for potential adverse pharmacokinetic kratom-drug interactions.

Hyperbaric Oxygen Therapy for Pain, Opioid Withdrawal, and Related Symptoms: A Pilot Randomized Controlled Trial.

Background: Pain, drug cravings, and opioid withdrawal symptoms can interfere with substance use disorder or opioid tapering treatment goals.

Aim: This pilot study investigated the feasibility of a protocol designed to test opioid withdrawal symptom relief relative to a sham condition after two consecutive days of hyperbaric oxygen therapy (HBOT) for adults prescribed daily methadone for opioid use disorder.

Method: Using a double-blind protocol, eight adults were randomized to receive either a full 90-minute HBOT dose in a pressurized chamber with 100% oxygen at 2.

Clinical Pharmacokinetic Assessment of Kratom (), a Botanical Product with Opioid-like Effects, in Healthy Adult Participants.

Increasing use of the botanical kratom to self-manage opioid withdrawal and pain has led to increased kratom-linked overdose deaths. Despite these serious safety concerns, rigorous fundamental pharmacokinetic knowledge of kratom in humans remains lacking. We assessed the pharmacokinetics of a single low dose (2 g) of a well-characterized kratom product administered orally to six healthy participants.

Sleep Deprivation and Sleep-Onset Insomnia are Associated with Blunted Physiological Reactivity to Stressors.

Introduction: Military operations often involve intense exposure to stressors combined with acute sleep deprivation, while military personnel also experience high prevalence of chronic sleep deficiency from insomnia and other sleep disorders. However, the impact of acute and chronic sleep deficiency on physiologic stressor responses is poorly understood. In a controlled laboratory study with normal sleepers and individuals with chronic sleep-onset insomnia, we measured responses to an acute stressor administered in a sleep deprivation condition or a control condition.

Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail.

The botanical natural product goldenseal can precipitate clinical drug interactions by inhibiting cytochrome P450 (CYP) 3A and CYP2D6. Besides P-glycoprotein, effects of goldenseal on other clinically relevant transporters remain unknown. Established transporter-expressing cell systems were used to determine the inhibitory effects of a goldenseal extract, standardized to the major alkaloid berberine, on transporter activity.

Robustness of inter-individual differences in slow wave sleep for daytime sleep periods after total sleep deprivation with or without caffeine administration: potential implications for around-the-clock operations.

There are large inter-individual differences in slow wave sleep, which constitute a trait or phenotype. We investigated whether the manifestation of this trait is impacted by daytime sleeping after sleep deprivation, and to what extent it is robust to prior caffeine intake. N = 12 subjects underwent three 48 h periods of total sleep deprivation with different caffeine dosing regimens.

C957T genotype modulates the time-on-task effect during total sleep deprivation.

Total sleep deprivation (TSD) and time-on-task (TOT), especially in combination, increase cognitive instability and cause performance impairment. There are large inter-individual differences in TSD and TOT effects which, in part, have a genetic basis. Here, we show that the dopamine receptor D C957T genetic polymorphism predicts the magnitude of the TOT effect on a psychomotor vigilance test (PVT) during 38 h of TSD.

Psychomotor Vigilance Impairment During Total Sleep Deprivation Is Exacerbated in Sleep-Onset Insomnia.

Purpose: Individuals with primary insomnia frequently report cognitive impairment as a next-day consequence of disrupted sleep. Studies attempting to quantify daytime impairment objectively in individuals with insomnia have yielded mixed results, with evidence suggesting impairments in aspects of executive functioning but not psychomotor vigilance. It has been suggested that persons with insomnia may have latent performance deficits for which they would be able to compensate effectively under normal daytime circumstances - suggesting that any such deficits may be exposed through perturbation.

Cannabis Use and Cognition in Adults Prescribed Opioids for Persistent Pain.

Background: Adults with persistent pain frequently report cannabis use to help manage their symptoms. The impact of cannabis use on cognition in the presence of concurrent symptoms of depression and anxiety is poorly understood.

Aims: Our study explored how cannabis use affects relationships among symptoms of depression, anxiety, and cognition.

Cardiac autonomic activity during sleep deprivation with and without caffeine administration.

Caffeine is often consumed to mitigate degraded alertness associated with sleep deprivation. Both caffeine and sleep deprivation have been implicated in cardiovascular disease, but evidence is largely anecdotal. We determined the effects of sleep deprivation and caffeine on markers of cardiac autonomic activity.

Cardiac autonomic activity during simulated shift work.

Shift work leads to adverse health outcomes including increased risk of cardiovascular disease. Heart rate (HR) and heart rate variability (HRV) are measures of cardiac autonomic activity and markers of cardiovascular disease and mortality. To investigate the effects of shift work on cardiac autonomic activity, we assessed the influence of simulated night work on HR and HRV, and dissociated the direct effects of circadian misalignment from those of sleep displacement and altered physical activity patterns.

Sex differences in opioid use and medical issues during buprenorphine/naloxone treatment.

Background: There are sex differences in buprenorphine/naloxone clinical trials for opioid use. While women have fewer opioid-positive urine samples, relative to men, a significant decrease in opioid-positive samples was found during treatment for men, but not women. In order to inform sex-based approaches to improve treatment outcomes, research is needed to determine if opioid use, and predictors of opioid use, differs between men and women during treatment.

3-minute smartphone-based and tablet-based psychomotor vigilance tests for the assessment of reduced alertness due to sleep deprivation.

The psychomotor vigilance test (PVT) is widely used to measure reduced alertness due to sleep loss. Here, two newly developed, 3-min versions of the psychomotor vigilance test, one smartphone-based and the other tablet-based, were validated against a conventional 10-min laptop-based PVT. Sixteen healthy participants (ages 22-40; seven males, nine females) completed a laboratory study, which included a practice and a baseline day, a 38-h total sleep deprivation (TSD) period, and a recovery day, during which they performed the three different versions of the PVT every 3 h.

Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults.

Context: There is a paucity of data describing the impact of type of beverage (coffee versus energy drink), different rates of consumption and different temperature of beverages on the pharmacokinetic disposition of caffeine. Additionally, there is concern that inordinately high levels of caffeine may result from the rapid consumption of cold energy drinks.

Objective: The objective of this study was to compare the pharmacokinetics of caffeine under various drink temperature, rate of consumption and vehicle (coffee versus energy drink) conditions.

Sleep and performance in simulated Navy watch schedules.

To operate Navy ships 24h per day, watchstanding is needed around the clock, with watch periods reflecting a variety of rotating or fixed shift schedules. The 5/15 watch schedule cycles through watch periods with 5h on, 15h off watch, such that watches occur 4h earlier on the clock each day - that is, the watches rotate backward. The timing of sleep varies over 4-day cycles, and sleep is split on some days to accommodate nighttime watchstanding.

Co-occurring mood disorders among hospitalized patients and risk for subsequent medical hospitalization.

Objective: The objective was to determine if patients hospitalized with a primary medical diagnosis and any co-occurring serious mental illness (SMI) were more likely than patients without any co-occurring SMI diagnosis to experience a subsequent medical hospitalization.

Method: This was a longitudinal cohort study of 925,705 adult persons (aged 18+ years). Patients hospitalized in Washington State from 2004 to 2008 were followed through 2009 (for an average of 43 months).