Functional role for cannabinoids in respiratory stability during sleep.

@article{Carley2002FunctionalRF,
  title={Functional role for cannabinoids in respiratory stability during sleep.},
  author={David W. Carley and Sasa Paviovic and Marina Janelidze and Miodrag G. Radulovacki},
  journal={Sleep},
  year={2002},
  volume={25 4},
  pages={
          391-8
        }
}
STUDY OBJECTIVES Serotonin, acting in the peripheral nervous system, can exacerbate sleep-related apnea, and systemically administered serotonin antagonists reduce sleep-disordered respiration in rats and bulldogs. Because cannabinoid receptor agonists are known to inhibit the excitatory effects of serotonin on nodose ganglion cells, we examined the effects of endogenous (oleamide) and exogenous (delta9-tetrahydrocannabinol; delta9THC) cannabimimetic agents on sleep-related apnea. DESIGN… 
View on PubMed
academic.oup.com
63 Citations
Background Citations
15
Methods Citations
1
Results Citations
1

Figures and Tables from this paper

63 Citations

Effects of Cannabinoid Agonists and Antagonists on Sleep and Breathing in Sprague-Dawley Rats
TLDR
Dronabinol's effects on apneas were dependent on CB1 receptor activation, while dronabinols effects on REM sleep were CB receptor-independent, according to a natural model of central sleep apnea.
Intranodose ganglion injections of dronabinol attenuate serotonin-induced apnea in Sprague-Dawley rat
Title : Intranodose ganglion injections of dronabinol attenuate serotonin-induced apnea in Sprague-Dawley rat
TLDR
It is shown that dronabinol injected locally into the nodose ganglia suppresses 5-HT-induced reflex apnea, and increases phasic, but not tonic, activation of the genioglossus, which supports the view that dRONabinol stabilizes respiratory pattern and augments upper airway muscles by acting at the nodoses ganglia.
Proof of Concept Trial of Dronabinol in Obstructive Sleep Apnea
TLDR
Dronabinol treatment is safe and well-tolerated in OSA patients at doses of 2.5–10 mg daily and significantly reduces AHI in the short-term and should be confirmed in a larger study in order to identify sub-populations with OSA that may benefit from cannabimimetic pharmacologic therapy.
Anandamide enhances extracellular levels of adenosine and induces sleep: an in vivo microdialysis study.
TLDR
Anandamide increased adenosine levels in the basal forebrain and also increased sleep in conditions where sleep may be severely attenuated, and this findings identify a potential therapeutic use of endocannabinoids to induce sleep in terms of dosage and mechanism.
Intracerebroventricular injections of dronabinol, a cannabinoid receptor agonist, does not attenuate serotonin-induced apnea in Sprague-Dawley rats
TLDR
The data show that ICV injection of dronabinol did not decrease 5-HT-induced apneas, and did not increase genioglossus activity, and this in contrast to published results of dRONabinol’s effect on apnea via the vagus nerve.
Effects of Cannabinoid Agonists and Antagonists on Sleep in Laboratory Animals.
TLDR
In this chapter, the studies detailing the effects of cannabinoids on sleep in laboratory animals are reviewed and some evidence suggests that some sleep effects may be elicited via non-cannabinoid receptor-dependent mechanisms.
DMSO potentiates the suppressive effect of dronabinol, a cannabinoid, on sleep apnea and REM sleep
TLDR
Dronabinol in 25% DMSO partially potentiated dronabinl’s effects, suggesting a concomitant biological effect of D MSO on breathing during sleep.
Clinical Management of Sleep and Sleep Disorders With Cannabis and Cannabinoids: Implications to Practicing Psychiatrists
TLDR
Preclinical investigations have demonstrated that combining the agent oleamide and THC aids in the stabilization of respiration in all stages of sleep as well as the maintenance of autonomic stability during sleep.
Pharmacology of vagal afferent influences on disordered breathing during sleep
...
...

References

SHOWING 1-10 OF 61 REFERENCES
Role of peripheral serotonin in the regulation of central sleep apneas in rats.
TLDR
It is concluded that binding at 5-HT3 receptors in the peripheral nervous system promotes REM-related apnea genesis in rats and suggests that endogenous 5-ht, acting at least at peripheral 5- HT3 receptors, may play a baseline physiologic role in the expression of spontaneous central apneas in rats.
Serotonin 5-HT3-receptor antagonist GR 38032F suppresses sleep apneas in rats.
TLDR
The authors' data implicate 5-HT3 receptor systems in determining sleep-related respiratory drive and apnea expression in rats, effects which are most probably mediated by vagal afferents.
The effects of ondansetron on sleep-disordered breathing in the English bulldog.
TLDR
Ondansetron had no effect on either sleep efficiency or sleep architecture, and there were no effects on either oxyhemoglobin saturation nadirs or on the sleep time with saturations <90%.
Mirtazapine, a mixed-profile serotonin agonist/antagonist, suppresses sleep apnea in the rat.
TLDR
It is concluded that mirtazapine, over a 50-fold dose range, significantly reduces central apnea expression during NREM and REM sleep in the rat and that the efficacy of this compound to suppress apnea in all sleep stages most probably arises from its mixed agonist/antagonist profile at serotonin receptors.
The effects of trazodone with L-tryptophan on sleep-disordered breathing in the English bulldog.
TLDR
Trazodone with L-tryptophan can treat sleep-disordered breathing (SDB) in an animal model of OSAHS; the effectiveness of this therapy may be related to increased upper airway dilator activity in sleep and/or enhanced slow-wave sleep.
The hypnotic actions of oleamide are blocked by a cannabinoid receptor antagonist.
TLDR
Data suggest that at least one aspect of the hypnotic action of OA involves interactions with the CB1 receptor system, possibly by blocking the metabolism of the endogenous CB1 cannabinoid-1 receptor agonist anandamide.
Brain lipids that induce sleep are novel modulators of 5-hydroxytrypamine receptors.
TLDR
Modulation of 5-HT2 receptors by ODA and related lipids may represent a novel mechanism for regulation of receptors that activate G proteins and thereby play a role in alertness, sleep, and mood as well as disturbances of these states.
L-tryptophan in the treatment of impaired respiration in sleep.
  • H. Schmidt
  • Biology, Medicine
    Bulletin europeen de physiopathologie respiratoire
  • 1983
TLDR
Serotoninergic activity with a defect in feedback control of tryptophan-serotonin metabolism is postulated as a potential mechanism in the pathophysiology of obstructive sleep apnea and the enhanced usefulness of L-T in combination with protriptyline is predicted.
Arousal-enhancing properties of the CB1 cannabinoid receptor antagonist SR 141716A in rats as assessed by electroencephalographic spectral and sleep-waking cycle analysis.
Response of obstructive sleep apnea to fluoxetine and protriptyline.
TLDR
Fluoxetine is beneficial to some, but not all, patients with OSA, and is better tolerated than protriptyline; however, for the group as a whole, there was no significant improvement in the number of arterial oxygen desaturation events, the level of arterIAL oxygen Desaturation, or the numberof arousals with either agent.
...
...