Endocannabinoid Signaling Regulates Sleep Stability

Pava, Matthew J.; Makriyannis, Alexandros; Lovinger, David M.

doi:10.1371/journal.pone.0152473

Cited by 64 publications

(70 citation statements)

References 82 publications

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“…However, evidence showing an apparent opposite modulatory role of the CB 1 cannabinoid receptor in sleep modulation has been published as well. In this regard, injection of the antagonist/inverse agonist AM281 of the CB 1 cannabinoid receptor immediately after TSD did not obstructed sleep rebound (Pava et al, 2016). Moreover, SWS was increased during the dark period after administrations of higher dose of CP47497, a cannabinoid receptor agonist, while reduction in this sleep stage was observed across the light period (Pava et al, 2016).…”

Section: Discussionmentioning

confidence: 90%

“…In this regard, injection of the antagonist/inverse agonist AM281 of the CB 1 cannabinoid receptor immediately after TSD did not obstructed sleep rebound (Pava et al, 2016). Moreover, SWS was increased during the dark period after administrations of higher dose of CP47497, a cannabinoid receptor agonist, while reduction in this sleep stage was observed across the light period (Pava et al, 2016). The intriguing but as yet unexplained results that CB 1 cannabinoid receptor modulates sleep raises questions about the mechanism of action implied.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, FAAH-KO mice display higher values of SWS (Huitro´n-Rese´ndiz et al, 2004) while the pharmacological inhibition of FAAH by administrations of URB597 in rats promotes waking (Murillo-Rodrı´guez et al, 2007, 2011. Conversely, it has been shown that administrations of FAAH inhibitor AM3506 promote an increase in SWS (Pava et al, 2016). According to the authors, mice treated with a systemic injection of AM3506 (10 mg/kg) during the dark period showed a significant enhancement in SWS whereas no effects across the light period were observed.…”

Section: Discussionmentioning

confidence: 99%

“…For example, dosage, sleep analysis procedure, species, pharmacological time administration, among other variables might provide an alternative reasonable explanation between opposite results. For instance, Pava et al (2016) used rotating disk paradigm for sleep deprivation studies whereas in the current report, gentle manipulation was handled. Differences in techniques used for sleep deprivation have provided different outcomes in intensity of sleep rebound (Rechtschaffen et al, 1999;Colavito et al, 2013;Pires et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

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Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

et al. 2016

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Abstract-The endocannabinoid system comprises receptors (CB 1 and CB 2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB 1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents. However, no further evidence is available regarding the neurobiological role of the endocannabinoid system in the homeostatic control of sleep. Therefore, the aim of the current experiment was to test if SR141716A, URB597 or VDM-11 would modulate the sleep rebound after sleep deprivation. Thus, these compounds were systemically injected (5, 10, 20 mg/kg; ip; separately each one) into rats after prolonged waking. We found that SR141716A and URB597 blocked in dose-dependent fashion the sleep rebound whereas animals treated with VDM-11 displayed sleep rebound during the recovery period. Complementary, injection after sleep deprivation of either SR141716A or URB597 enhanced dose-dependently the extracellular levels of dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT), as well as adenosine (AD) while VDM-11 caused a decline in contents of these molecules. These findings suggest that SR141716A or URB597 behave as a potent stimulants since they suppressed the sleep recovery period after prolonged waking. It can be concluded that elements of the endocannabinoid system, such as the CB 1 cannabinoid receptor, FAAH and AMT, modulate the sleep homeostasis after prolonged waking. Ó

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

et al. 2016

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“…For instance, cumulative evidence has suggested that the elements of the endocannabinoid system, including FAAH, control the sleep-wake cycle (Santucci et al, 1996; Murillo-Rodríguez et al, 1998, 2001, 2003, 2008a, 2011a, 2013, 2016; Herrera-Solis et al, 2010; Rueda-Orozco et al, 2010; Pava et al, 2014, 2016). In this regard, an experimental approach to explore the role of FAAH in sleep modulation has consisted in the characterization of the properties of FAAH inhibitors, such as URB597 (Murillo-Rodríguez et al, 2007b, 2011a, 2016).…”

Section: Discussionmentioning

confidence: 99%

Role of N-Arachidonoyl-Serotonin (AA-5-HT) in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation

Murillo-Rodrı́guez

Marzo

Machado

et al. 2017

Front. Mol. Neurosci.

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The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)], receptors (CB1 and CB2), enzymes such as [fatty acid amide hydrolase (FAHH) and monoacylglycerol lipase (MAGL)], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep–wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1), N-arachidonoyl-serotonin (AA-5-HT) in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p.) injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W) and increased slow wave sleep (SWS) as well as rapid eye movement sleep (REMS). Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT) whereas the levels of adenosine (AD) were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD) or modafinil (MOD) during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD). The injection of CBD or MOD increased alertness during sleep rebound period after TSD. However, AA-5-HT blocked this effect by allowing animals to display an enhancement in sleep across sleep rebound period. Overall, our findings provide evidence that AA-5-HT is an important modulator of sleep, sleep homeostasis and neurotransmitter contents.

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Measuring Disturbance of the Endocannabinoid System in Psychosis

et al. 2019

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IMPORTANCEThe endocannabinoid system (ECS) is a lipid-based endogenous signaling system. Its relevance to psychosis is through the association between cannabis use and the onset and course of illness and through the antipsychotic properties of cannabidiol, a potential ECS enhancer.OBJECTIVE To conduct a systematic review and meta-analysis of the blood and cerebrospinal fluid (CSF) measures of the ECS in psychotic disorders.DATA SOURCES Web of Science and PubMed were searched from inception through June 13, 2018. The articles identified were reviewed, as were citations to previous publications and the reference lists of retrieved articles.STUDY SELECTION Original articles were included that reported blood or CSF measures of ECS activity in patients with psychotic illnesses and in healthy controls.DATA EXTRACTION AND SYNTHESIS PRISMA guidelines, independent extraction by multiple observers, and random-effects meta-analysis were used. Heterogeneity was assessed with the I 2 index. Sensitivity analyses tested the robustness of the results. MAIN OUTCOMES AND MEASURESThe clinical relevance of ECS modifications in psychotic disorders was investigated by (1) a quantitative synthesis of the differences in blood and CSF markers of the ECS between patients and healthy controls, and (2) a qualitative synthesis of the association of these markers with symptom severity, stage of illness, and response to treatment. RESULTS A total of 18 studies were included. Three individual meta-analyses were performed to identify the differences in ECS markers between people with schizophrenia and healthy controls. Five studies, including 226 patients and 385 controls, reported significantly higher concentrations of anandamide in the CSF of patients than controls (standardized mean difference [SMD], 0.97; 95% CI, 0.67-1.26; P < .001; I 2 = 54.8%). In 9 studies, with 344 patients and 411 controls, significantly higher anandamide levels in blood were found in patients, compared with controls (SMD, 0.55; 95% CI, 0.05-1.04; P = .03; I 2 = 89.6%). In 3 studies, involving 88 patients and 179 controls, a significantly higher expression of type 1 cannabinoid receptors on peripheral immune cells was reported in patients compared with controls (SMD, 0.57; 95% CI, 0.31-0.84; P < .001; I 2 = 0%). Higher ECS tone was found at an early stage of illness in individuals who were antipsychotic naïve or free, and it had an inverse association with symptom severity and was normalized after successful treatment. Moderate to high level of heterogeneity in methods was found between studies. CONCLUSIONS AND RELEVANCETesting clinically relevant markers of the ECS in the blood and CSF of people with psychotic illness appears possible, and these markers provide useful biomarkers for the psychotic disorder; however, not all studies accounted for important variables, such as cannabis use.

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Endocannabinoid Signaling Regulates Sleep Stability

Cited by 64 publications

References 82 publications

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

Role of N-Arachidonoyl-Serotonin (AA-5-HT) in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation

Measuring Disturbance of the Endocannabinoid System in Psychosis

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