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Article ; Online: DMSO potentiates the suppressive effect of dronabinol on sleep apnea and REM sleep in rats.

Calik, Michael W / Carley, David W

Journal of cannabis research

2023 Volume 5, Issue 1, Page(s) 30

Abstract: Introduction: Dimethyl sulfoxide (DMSO) is an amphipathic molecule with innate biological activity that also is used to dissolve both polar and nonpolar compounds in preclinical and clinical studies. Recent investigations of dronabinol, a cannabinoid, ... ...

Abstract	Introduction: Dimethyl sulfoxide (DMSO) is an amphipathic molecule with innate biological activity that also is used to dissolve both polar and nonpolar compounds in preclinical and clinical studies. Recent investigations of dronabinol, a cannabinoid, dissolved in DMSO demonstrated decreased sleep apnea frequency and time spent in REM sleep in rats. Here, we tested the effects of dronabinol dissolved in 25% DMSO diluted in phosphate-buffered saline (PBS) to rule out potentiating effects of DMSO. Methods: Sprague-Dawley rats were anesthetized and implanted with bilateral stainless steel screws into the skull for electroencephalogram recording and bilateral wire electrodes into the nuchal muscles for electromyogram recording. Each animal was recorded by polysomnography. The study was a fully nested, repeated measures crossover design, such that each rat was recorded following each of 8 intraperitoneal injections separated by three days: vehicle (25% DMSO/PBS); vehicle and CB Results: Dronabinol dissolved in 25% DMSO did not suppress sleep apneas or modify sleep efficiency compared to vehicle controls, in contrast to previously published results. However, dronabinol did suppress REM sleep, which is in line with previously published results. Conclusions: Dronabinol in 25% DMSO partially potentiated dronabinol's effects, suggesting a concomitant biological effect of DMSO on breathing during sleep.
Language	English
Publishing date	2023-07-28
Publishing country	England
Document type	Journal Article
ISSN	2522-5782
ISSN (online)	2522-5782
DOI	10.1186/s42238-023-00199-4
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Book: Sleep related breathing disorders

Carley, David W.

experimental models and therapeutic potential

(Lung biology in health and disease ; 171)

2003

Title variant	Sleep-related breathing disorders
Author's details	ed. by David W. Carley
Series title	Lung biology in health and disease ; 171
Collection
Keywords	Sleep Apnea Syndromes ; Schlafapnoe ; Tiermodell ; Schlaf ; Atemstörung
Subject	Atmungsstörung ; Schlafapnoe-Syndrom ; Obstruktives Schlaf-Apnoe-Syndrom
Language	English
Size	XV, 385 S. : Ill., graph. Darst.
Publisher	Dekker
Publishing place	New York u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT013553644
ISBN	0-8247-0877-6 ; 978-0-8247-0877-1
Database	Catalogue ZB MED Medicine, Health

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2003 A 2296	order for loan	Magazin

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Article ; Online: Effects of Cannabinoid Agonists and Antagonists on Sleep and Breathing in Sprague-Dawley Rats.

Calik, Michael W / Carley, David W

Sleep

2017 Volume 40, Issue 9

Abstract: Study objectives: There are no pharmacological treatments for obstructive sleep apnea syndrome, but dronabinol showed promise in a small pilot study. In anesthetized rats, dronabinol attenuates reflex apnea via activation of cannabinoid (CB) receptors ... ...

Abstract	Study objectives: There are no pharmacological treatments for obstructive sleep apnea syndrome, but dronabinol showed promise in a small pilot study. In anesthetized rats, dronabinol attenuates reflex apnea via activation of cannabinoid (CB) receptors located on vagal afferents; an effect blocked by cannabinoid type 1 (CB1) and/or type 2 (CB2) receptor antagonists. Here, using a natural model of central sleep apnea, we examine the effects of dronabinol, alone and in combination with selective antagonists in conscious rats chronically instrumented to stage sleep and measure cessation of breathing. Methods: Adult male Sprague-Dawley rats were anesthetized and implanted with bilateral stainless steel screws into the skull for electroencephalogram recording and bilateral wire electrodes into the nuchal muscles for electromyogram recording. Each animal was recorded by polysomnography on multiple occasions separated by at least 3 days. The study was a fully nested, repeated measures crossover design, such that each rat was recorded following each of 8 intraperitoneal injections: vehicle; vehicle and CB1 antagonist (AM 251); vehicle and CB2 antagonist (AM 630); vehicle and CB1/CB2 antagonist; dronabinol; dronabinol and CB1 antagonist; dronabinol and CB2 antagonist; and dronabinol and CB1/CB2 antagonist. Results: Dronabinol decreased the percent time spent in rapid eye movement (REM) sleep. CB receptor antagonists did not reverse this effect. Dronabinol also decreased apneas during sleep, and this apnea suppression was reversed by CB1 or CB1/CB2 receptor antagonism. Conclusions: Dronabinol's effects on apneas were dependent on CB1 receptor activation, while dronabinol's effects on REM sleep were CB receptor-independent.
MeSH term(s)	Animals ; Cannabinoid Receptor Agonists/pharmacology ; Cannabinoid Receptor Agonists/therapeutic use ; Cannabinoid Receptor Antagonists/pharmacology ; Cannabinoid Receptor Antagonists/therapeutic use ; Disease Models, Animal ; Dronabinol/pharmacology ; Dronabinol/therapeutic use ; Electroencephalography ; Electromyography ; Indoles/pharmacology ; Male ; Piperidines/pharmacology ; Polysomnography ; Pyrazoles/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1/agonists ; Receptor, Cannabinoid, CB1/antagonists & inhibitors ; Receptor, Cannabinoid, CB1/metabolism ; Receptor, Cannabinoid, CB2/agonists ; Receptor, Cannabinoid, CB2/antagonists & inhibitors ; Receptor, Cannabinoid, CB2/metabolism ; Respiration/drug effects ; Sleep/drug effects ; Sleep Apnea, Central/drug therapy ; Sleep Apnea, Central/physiopathology ; Sleep, REM/drug effects ; Vagus Nerve/physiology
Chemical Substances	Cannabinoid Receptor Agonists ; Cannabinoid Receptor Antagonists ; Indoles ; Piperidines ; Pyrazoles ; Receptor, Cannabinoid, CB1 ; Receptor, Cannabinoid, CB2 ; AM 251 (3I4FA44MAI) ; Dronabinol (7J8897W37S) ; iodopravadoline (U1LNJ6NBKA)
Language	English
Publishing date	2017--01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	424441-2
ISSN	1550-9109 ; 0161-8105
ISSN (online)	1550-9109
ISSN	0161-8105
DOI	10.1093/sleep/zsx112
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Article: Vikrahraun-the 1961 basaltic lava flow eruption at Askja, Iceland: morphology, geochemistry, and planetary analogs.

Blasizzo, Aline Y / Ukstins, Ingrid A / Scheidt, Stephen P / Graettinger, Alison H / Peate, David W / Carley, Tamara L / Moritz, Adam J / Thines, Jennifer E

Earth, planets, and space : EPS

2022 Volume 74, Issue 1, Page(s) 168

Language	English
Publishing date	2022-11-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2087663-4
ISSN	1880-5981 ; 1343-8832
ISSN (online)	1880-5981
ISSN	1343-8832
DOI	10.1186/s40623-022-01711-5
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Article ; Online: Intracerebroventricular injections of dronabinol, a cannabinoid receptor agonist, does not attenuate serotonin-induced apnea in Sprague-Dawley rats.

Calik, Michael W / Carley, David W

Journal of negative results in biomedicine

2016 Volume 15, Page(s) 8

Abstract: Background: Evidence suggests that vagal nerve activity may play a role in sleep apnea induction. In anesthetized rats, dronabinol, a cannabinoid (CB) receptor agonist, injected into the nodose ganglia attenuates reflex apnea and increases genioglossus ... ...

Abstract	Background: Evidence suggests that vagal nerve activity may play a role in sleep apnea induction. In anesthetized rats, dronabinol, a cannabinoid (CB) receptor agonist, injected into the nodose ganglia attenuates reflex apnea and increases genioglossus activity, and reflex apnea attenuation is blocked by systemic pre-treatment with cannabinoid type 1 and/or type 2 receptor antagonists. However, it is unclear whether dronabinol has similar effects in the central nervous system; CB receptors are widely distributed in the brain, especially on neuronal circuitry important for respiration and upper airway activation. Here, we examine the effects of intracerebroventricular (ICV) injection of dronabinol on serotonin (5-HT)-induced apnea. Methods: Adult male Sprague-Dawley rats were anesthetized and instrumented with bilateral electrodes to monitor genioglossi EMG and with a piezoelectric strain gauge to monitor respiratory pattern. Serotonin was intravenously infused into a femoral vein to induce reflex apnea. After baseline recordings, rats were placed in a stereotaxic apparatus. A unilateral osteotomy was made to allow access for injection to the right lateral ventricle, and the dura were carefully removed. Dronabinol (100, 10, 1, or 0.1 μg/3 μl DMSO) or control (3 μl DMSO) was injected into the right lateral ventricle and 5-HT infusion was repeated. Data (mean ± SEM) were analyzed using a mixed model analysis with a repeated/fixed measure. Results: There was no main effect in 5-HT-induced apnea or breath duration, or in breath instability, between ICV dronabinol injected and ICV vehicle control injected groups. Moreover, there was no main effect in phasic or tonic genioglossus activity between ICV dronabinol injected and ICV vehicle control injected groups. Conclusion: Our data show that ICV injection of dronabinol did not decrease 5-HT-induced apneas, and did not increase genioglossus activity. This in contrast to published results of dronabinol's effect on apnea via the vagus nerve. Our results suggest that the effects of dronabinol on reflex apneas are peripherally mediated via suppression of vagal nerve activity.
MeSH term(s)	Animals ; Apnea/chemically induced ; Apnea/physiopathology ; Apnea/prevention & control ; Cannabinoid Receptor Agonists/administration & dosage ; Cannabinoid Receptor Agonists/pharmacology ; Dronabinol/administration & dosage ; Dronabinol/pharmacology ; Electromyography ; Injections, Intraventricular ; Male ; Rats ; Rats, Sprague-Dawley ; Serotonin/administration & dosage
Chemical Substances	Cannabinoid Receptor Agonists ; Serotonin (333DO1RDJY) ; Dronabinol (7J8897W37S)
Language	English
Publishing date	2016-05-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2091480-5
ISSN	1477-5751 ; 1477-5751
ISSN (online)	1477-5751
ISSN	1477-5751
DOI	10.1186/s12952-016-0052-1
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Article: Physiology of Sleep.

Carley, David W / Farabi, Sarah S

Diabetes spectrum : a publication of the American Diabetes Association

2015 Volume 29, Issue 1, Page(s) 5–9

Abstract: IN BRIEF Far from a simple absence of wakefulness, sleep is an active, regulated, and metabolically distinct state, essential for health and well-being. In this article, the authors review the fundamental anatomy and physiology of sleep and its ... ...

Abstract	IN BRIEF Far from a simple absence of wakefulness, sleep is an active, regulated, and metabolically distinct state, essential for health and well-being. In this article, the authors review the fundamental anatomy and physiology of sleep and its regulation, with an eye toward interactions between sleep and metabolism.
Language	English
Publishing date	2015-11-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211544-4
ISSN	1040-9165
ISSN	1040-9165
DOI	10.2337/diaspect.29.1.5
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Article ; Online: Co-creating a suite of patient decision aids for parents of an infant or young child with differences of sex development: A methods roadmap.

Lightfoot, Sophie / Carley, Meg / Brinkman, William / Gardner, Melissa D / Gruppen, Larry D / Liang, Noi / Pinkelman, Kendra / Speiser, Phyllis W / Suorsa-Johnson, Kristina I / VanderBrink, Brian / Wisniewski, Jessica / Sandberg, David E / Stacey, Dawn

Frontiers in urology

2023 Volume 2

Abstract: Introduction: Parents and guardians of infants and young children with differences of sex development (DSD) often face numerous health and social decisions about their child's condition. While proxy health decisions can be stressful in any circumstance, ...

Abstract	Introduction: Parents and guardians of infants and young children with differences of sex development (DSD) often face numerous health and social decisions about their child's condition. While proxy health decisions can be stressful in any circumstance, they are further exacerbated in this clinical context by significant variations in clinical presentation, parental lack of knowledge about DSD, irreversibility of some options (e.g., gonadectomy), a paucity of research available about long-term outcomes, and anticipated decisional regret. This study aimed to engage clinicians, parents, and an adult living with DSD to collaboratively develop a suite of patient decision aids (PDAs) to respond to the decisional needs of parents and guardians of infants and young children diagnosed with DSD. Methods: We used a systematic co-development process guided by the Ottawa Decision Support Framework and the International Patient Decision Aids Standards (IPDAS). The five steps were: literature selection, establish the team, decisional needs assessment, create the PDAs, and alpha testing. Results: We developed four PDAs to support parents/guardians of infants or young children diagnosed with DSD about four priority decisions identified through our decisional needs assessment: genetic testing, gender of rearing, genital surgery and gonadal surgery. All four PDAs include information for parents about DSD, the options, reasons to choose or avoid each option, and opportunities for parents/guardians to rate the importance of features of each option to clarify their values for these features. Qualitative feedback was positive from clinicians, parents and an adult living with DSD. Conclusions: These PDAs are clinical tools designed to support parents/guardians and to promote making an informed and shared DSD-related decision. While these tools are specific to DSD, they contain themes and elements translatable to other pediatric populations.
Language	English
Publishing date	2023-01-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	3123829-4
ISSN	2673-9828 ; 2673-9828
ISSN (online)	2673-9828
ISSN	2673-9828
DOI	10.3389/fruro.2022.1020152
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Article ; Online: Prevalence and Correlates of Insomnia in People Living With HIV in Indonesia: A Descriptive, Cross-sectional Study.

Pujasari, Hening / Culbert, Gabriel J / Levy, Judith A / Steffen, Alana / Carley, David W / Kapella, Mary C

The Journal of the Association of Nurses in AIDS Care : JANAC

2020 Volume 31, Issue 5, Page(s) 606–614

MeSH term(s)	Adult ; Anti-HIV Agents/administration & dosage ; Antiretroviral Therapy, Highly Active ; Anxiety/epidemiology ; Anxiety/psychology ; Cross-Sectional Studies ; Depression/epidemiology ; Depression/psychology ; Female ; HIV Infections/complications ; HIV Infections/drug therapy ; HIV Infections/psychology ; Humans ; Indonesia/epidemiology ; Male ; Medication Adherence ; Middle Aged ; Prevalence ; Quality of Life ; Risk Factors ; Sleep Initiation and Maintenance Disorders/epidemiology ; Sleep Initiation and Maintenance Disorders/etiology ; Sleep Initiation and Maintenance Disorders/psychology ; Substance-Related Disorders/epidemiology ; Substance-Related Disorders/psychology
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2020-08-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1159376-3
ISSN	1552-6917 ; 1055-3290
ISSN (online)	1552-6917
ISSN	1055-3290
DOI	10.1097/JNC.0000000000000192
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Article ; Online: Cannabinoid type 1 and type 2 receptor antagonists prevent attenuation of serotonin-induced reflex apneas by dronabinol in Sprague-Dawley rats.

Calik, Michael W / Carley, David W

PloS one

2014 Volume 9, Issue 10, Page(s) e111412

Abstract: The prevalence of obstructive sleep apnea (OSA) in Americans is 9% and increasing. Increased afferent vagal activation may predispose to OSA by reducing upper airway muscle activation/patency and disrupting respiratory rhythmogenesis. Vagal afferent ... ...

Abstract	The prevalence of obstructive sleep apnea (OSA) in Americans is 9% and increasing. Increased afferent vagal activation may predispose to OSA by reducing upper airway muscle activation/patency and disrupting respiratory rhythmogenesis. Vagal afferent neurons are inhibited by cannabinoid type 1 (CB1) or cannabinoid type 2 (CB2) receptors in animal models of vagally-mediated behaviors. Injections of dronabinol, a non-selective CB1/CB2 receptor agonist, into the nodose ganglia reduced serotonin (5-HT)-induced reflex apneas. It is unknown what role CB1 and/or CB2 receptors play in reflex apnea. Here, to determine the independent and combined effects of activating CB1 and/or CB2 receptors on dronabinol's attenuating effect, rats were pre-treated with CB1 (AM251) and/or CB2 (AM630) receptor antagonists. Adult male Sprague-Dawley rats were anesthetized, instrumented with bilateral electrodes to monitor genioglossus electromyogram (EMGgg) and a piezoelectric strain gauge to monitor respiratory pattern. Following intraperitoneal treatment with AM251 and/or AM630, or with vehicle, serotonin was intravenously infused into a femoral vein to induce reflex apnea. After baseline recordings, the nodose ganglia were exposed and 5-HT-induced reflex apneas were again recorded to confirm that the nerves remained functionally intact. Dronabinol was injected into each nodose ganglion and 5-HT infusion was repeated. Prior to dronabinol injection, there were no significant differences in 5-HT-induced reflex apneas or phasic and tonic EMGgg before or after surgery in the CB1, CB2, combined CB1/CB2 antagonist, and vehicle groups. In the vehicle group, dronabinol injections reduced 5-HT-induced reflex apnea duration. In contrast, dronabinol injections into nodose ganglia of the CB1, CB2, and combined CB1/CB2 groups did not attenuate 5-HT-induced reflex apnea duration. However, the CB1 and CB2 antagonists had no effect on dronabinol's ability to increase phasic EMGgg. These findings underscore the therapeutic potential of dronabinol in the treatment of OSA and implicate participation of both cannabinoid receptors in dronabinol's apnea suppression effect.
MeSH term(s)	Animals ; Cannabinoid Receptor Agonists/chemistry ; Dronabinol/chemistry ; Electromyography ; Femoral Vein/pathology ; Indoles/chemistry ; Male ; Nodose Ganglion/drug effects ; Piperidines/chemistry ; Pyrazoles/chemistry ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1/antagonists & inhibitors ; Receptor, Cannabinoid, CB2/antagonists & inhibitors ; Serotonin/administration & dosage ; Serotonin/chemistry ; Sleep Apnea, Obstructive/chemically induced ; Sleep Apnea, Obstructive/drug therapy ; Treatment Outcome
Chemical Substances	Cannabinoid Receptor Agonists ; Indoles ; Piperidines ; Pyrazoles ; Receptor, Cannabinoid, CB1 ; Receptor, Cannabinoid, CB2 ; Serotonin (333DO1RDJY) ; AM 251 (3I4FA44MAI) ; Dronabinol (7J8897W37S) ; iodopravadoline (U1LNJ6NBKA)
Language	English
Publishing date	2014-10-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0111412
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Article ; Online: Relating three-dimensional airway measurements to the apnea-hypopnea index in pediatric sleep apnea patients.

Masoud, Ahmed I / Alwadei, Abdurahman H / Gowharji, Lena F / Park, Chang G / Carley, David W

Orthodontics & craniofacial research

2020 Volume 24, Issue 1, Page(s) 137–146

Abstract: Objectives: (a) To evaluate three-dimensional radiographic airway analysis as it relates to the pre-test probability for sleep apnea in pediatric patients, and (b) to develop cut-off values for measurements showing promising results.: Setting and ... ...

Abstract	Objectives: (a) To evaluate three-dimensional radiographic airway analysis as it relates to the pre-test probability for sleep apnea in pediatric patients, and (b) to develop cut-off values for measurements showing promising results. Setting and sample population: A consecutive series of pediatric patients between the ages of 7 and 17 years, referred for a sleep study were recruited. Cone beam computed tomography (CBCT) scans were acquired for 103 subjects within one month following the sleep study. Methods: Three-dimensional airway analysis was performed including volumetric, area and linear measurements. Correlations with the apnea-hypopnea index (AHI) and receiver operating characteristic (ROC) curves were constructed. Sensitivity and specificity were calculated for prediction of AHI ≥ 5 and AHI ≥ 10. Results: 99 CBCT scans were included (median age = 11 years). The nasopharyngeal volume (NPV) significantly correlated with AHI (rho≈-0.4, P < .05). In subjects aged 7-11 years, proposed cut-off values for NPV are 2400mm Conclusions: Contrary to findings in adults, the NPV shows promise when screening for sleep apnea in children when CBCT scans are available. The OCSA might also be of value when screening for sleep apnea especially in older children.
MeSH term(s)	Adolescent ; Adult ; Aged ; Child ; Humans ; Oropharynx ; Polysomnography ; ROC Curve ; Sleep Apnea Syndromes/diagnostic imaging ; Sleep Apnea, Obstructive/diagnostic imaging
Language	English
Publishing date	2020-09-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2076514-9
ISSN	1601-6343 ; 1601-6335
ISSN (online)	1601-6343
ISSN	1601-6335
DOI	10.1111/ocr.12417
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