Cited by 59Cannabis and Cannabinoid ResearchSleep and Wakefulness ResearchSleep and Work-Related Fatigue

Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans

Open access
Cedernaes, Jonathan, Fanelli, Flaminia, Fazzini, Alessia, Pagotto, Uberto, Broman, Jan-Erik, Vogel, Heike, Dickson, Suzanne L., Schiöth, Helgi B. +1 more·2016·Psychoneuroendocrinology

Abstract

Following binding to cannabinoid receptors, endocannabinoids regulate a variety of central nervous system processes including appetite and mood. Recent evidence suggests that the systemic release of these lipid metabolites can be altered by acute exercise and that their levels also vary across the 24-h sleep-wake cycle. The present study utilized a within-subject design (involving 16 normal-weight men) to determine whether daytime circulating endocannabinoid concentrations differ following three nights of partial sleep deprivation (4.25-h sleep opportunity, 2:45-7a.m. each night) vs. normal sleep (8.5-h sleep opportunity, 10:30p.m.-7a.m. each night), before and after an acute bout of ergometer cycling in the morning. In addition, subjective hunger and stress were measured. Pre-exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher 1.5h after awakening (vs. normal sleep, p<0.05) when participants were sleep-deprived. This coincided with increased hunger ratings (+25% vs. normal sleep, p<0.05). Moreover, plasma 2AG was elevated 15min post-exercise (+44%, p<0.05). Sleep duration did not however modulate this exercise-induced rise. Finally, subjective stress was generally lower on the day after three nights of short sleep vs. normal sleep, especially after exercise (p<0.05). Given that activation of the endocannabinoid system has been previously shown to acutely increase appetite and mood, our results could suggest that behavioral effects of acute sleep loss, such as increased hunger and transiently improved psychological state, may partially result from activation of this signaling pathway. In contrast, more pronounced exercise-induced elevations of endocannabinoids appear to be less affected by short sleep duration.

AI snapshot

Written from the paper’s full text.

TL;DR

In 16 healthy normal-weight men, three nights of partial sleep restriction increased fasting morning plasma 2-arachidonoylglycerol (2AG) before exercise and coincided with higher hunger, but sleep duration did not alter the exercise-induced rise in 2AG. Acute ergometer cycling transiently raised 2AG at 15 min post-exercise, while subjective stress was generally lower after short sleep.

Key findings

  • Pre-exercise morning plasma 2AG was 80% higher after short vs normal sleep (3.99 ± 0.74 vs 2.22 ± 0.21 pmol/ml, p = 0.014), with no difference the prior evening (p = 0.830); hunger was also +25% higher at 8:30 a.m. after short sleep (p = 0.034).
  • Exercise increased plasma 2AG at 15 min post-exercise (+44%; 2.94 ± 0.40 vs 2.04 ± 0.16 pmol/ml, p = 0.012), and this rise did not differ by sleep condition; OEA differed only between pre-exercise and 4 h post-exercise (7.42 ± 0.33 vs 6.29 ± 0.33 pmol/ml, p = 0.001).
  • AEA and PEA showed no significant main effects of exercise time point (p ≥ 0.058), and AEA, PEA, and OEA did not differ between sleep conditions.
  • Subjective stress was generally lower after short sleep vs normal sleep (main effect p = 0.010), especially after exercise, but no correlations were found between hunger or stress ratings and plasma endocannabinoid concentrations (Pearson r range −0.072 to 0.159, p ≥ 0.210).

Methods

  • Within-subject, randomized, counterbalanced design in 16 healthy non-smoking normal-weight men (age 22.9 ± 0.66 years; BMI 22.9 ± 0.46 kg/m²), comparing three nights of normal sleep (8.5-h opportunity, 10:30 p.m.–7 a.m.) vs partial sleep restriction (4.25-h opportunity, 2:45–7 a.m.).
  • On day 4, fasted participants completed 35 min of ergometer cycling (5-min warm-up at 25% workload, then 30 min at 75% VO₂ reserve; average 177 ± 10 W); blood was sampled at day 3 7:30 p.m., day 4 8:30 a.m., ∼10 a.m., ∼15 min post-exercise, and ∼4 h post-exercise, with plasma 2AG (sum of 1AG + 2AG), AEA, PEA, and OEA measured by LC-MS/MS.
  • Hunger and stress were rated on 100-mm visual analogue scales at 8:30 a.m., ∼10 a.m., ∼11 a.m., and ∼3 p.m.; repeated measures ANOVA with Greenhouse-Geisser correction and Pearson correlations were used, with two-tailed p < 0.05 considered significant.

Limitations

  • The paper states that sleep-disorder breathing cannot be completely ruled out because the adaptation-night polysomnography lacked respiratory recordings, though this was considered unlikely in young, normal-weight, healthy participants; it also states that generalizability to females, older participants, obese humans under short sleep, or exercise after an energy preload is unknown.
  • The paper notes that sleep deprivation may have modulated post-exercise endocannabinoid concentrations before, between, or after the measured 15-min and 4-h post-exercise time points, and that the late OEA rise could reflect circadian fluctuation or extended fasting rather than exercise.
  • Evident from the text: the sample was small (16 men only), the study used a single exercise intensity and morning timing, and no correlations supported a direct mediation of hunger or stress by circulating endocannabinoids.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.psyneuen.2016.09.014

Cites

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Statistics

Claims the paper makes

0 of 58 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    No differences in plasma 2AG were observed in the evening of day 3 between sleep conditions (p=0.830).

    “No differences were, however, observed in the evening of day 3 (i.e., following 2 experimental nights) between sleep conditions (p = 0.830, pairwise t-test comparison; Fig. 2A).”
    Quote in the paperSubstantial claim
  • Findingown data

    In the morning of day 4 at 8:30 a.m. following 3 experimental nights, plasma 2AG concentrations were on average 80% higher in the short vs normal sleep condition (3.99 ± 0.74 vs 2.22 ± 0.21 pmol/ml, p=0.014).

    “In the morning of day 4 (i.e., at 8:30 a.m.following 3 experimental nights), plasma concentrations of 2AG were on average +80% higher in the short vs. normal sleep condition (3.99 ± 0.74 vs. 2.22 ± 0.21 pmol/ml, df = 15, t = 2.78, p = 0.014; Fig. 2A).”
    • Also stated in: § Abstract · plain
      “Pre-exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher 1.5 h after awakening (vs.normal sleep, p < 0.05) when participants were sleep-deprived.”
    Quote in the paperSubstantial claim
  • Findingown data

    There was a main effect of Exercise time point on plasma OEA concentrations (p≤0.036).

    “In contrast, main effects of Exercise time point on plasma concentrations of 2AG and OEA were found (p ≤ 0.036 for all main effects of Exercise time point; Table 1).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Plasma 2AG was significantly higher 15 min post-exercise than pre-exercise (2.94 ± 0.40 vs 2.04 ± 0.16 pmol/ml, p=0.012, Bonferroni-corrected).

    “Post-hoc comparisons revealed that plasma concentrations of 2AG were only significantly different when pre-exercise and 15 min post-exercise time points were compared (15 min post-exercise vs. pre-exercise: 2.94 ± 0.40 vs. 2.04 ± 0.16 pmol/ml, p = 0.012; +4 h post-exercise, 2.25 ± 0.22 pmol/ml vs. pre-exercise: p = 0.196; 4 h post-exercise vs. 15 min post-exercise:p = 0.093; all Bonferroni-correct”
    Quote in the paperSubstantial claim
  • Findingown data

    Plasma OEA did not differ significantly between 15 min post-exercise and pre-exercise (6.77 ± 0.45 vs 6.29 ± 0.33 pmol/ml, p=0.896, Bonferroni-corrected).

    “Finally, plasma concentrations of OEA differed only between preexercise and 4 h post-exercise time points (15 min post-exercise vs. pre-exercise: 6.77 ± 0.45 vs. 6.29 ± 0.33 pmol/ml, p = 0.896; 4 h post-exercise, 7.42 ± 0.33 pmol/ml, vs. pre-exercise: p = 0.001; 4 h post-exercise vs. 15 min post-exercise:p = 0.466; all Bonferronicorrected; Fig. 3D).”
    Quote in the paperSubstantial claim
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    Findingown data

    There was a main effect of time on plasma PEA concentrations across all time points and both sleep conditions (p<0.001), with lowest at 8:30 a.m. day 4 (14.48 ± 0.53 pmol/ml) and highest at ~3 p.m. day 4 (18.58 ± 0.68 pmol/ml).

    “PEA (p < 0.001, lowest concentration at 8:30 a.m. on day 4, 14.48 ± 0.53 pmol/ml; highest concentration at ∼3 p.m. on day 4, 18.58 ± 0.68 pmol/ml)”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    In the normal sleep condition, subjects slept 7.95 ± 0.13 h, 7.91 ± 0.10 h, and 8.02 ± 0.10 h on nights 1-3.

    “In the normal sleep condition (i.e., where subjects could sleep for 8.5 h each night), the polysomnographic analysis revealed that subjects slept in total 7.95 ± 0.13 h on the first night, 7.91 ± 0.10 h on the second night, and 8.02 ± 0.10 h on the third night.”
    Quote in the paperNot a substantial claim
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    Findingown data

    There was a main effect of time on plasma AEA concentrations across all time points and both sleep conditions (p<0.001), with lowest at 8:30 a.m. day 4 (0.82 ± 0.04 pmol/ml) and highest at 7:30 p.m. day 3 (1.16 ± 0.06 pmol/ml).

    “AEA (p < 0.001, lowest concentration at 8:30 a.m. on day 4, 0.82 ± 0.04 pmol/ml; highest concentration at 7:30 p.m. on day 3, 1.16 ± 0.06 pmol/ml)”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    There was a main effect of time on plasma OEA concentrations across all time points and both sleep conditions (p<0.001), with lowest at 8:30 a.m. day 4 (5.18 ± 0.26 pmol/ml) and highest at ~3 p.m. day 4 (7.42 ± 0.33 pmol/ml).

    “OEA (p < 0.001, lowest concentration at 8:30 a.m. on day 4, 5.18 ± 0.26 pmol/ml; highest concentration at ∼3 p.m. on day 4, 7.42 ± 0.33 pmol/ml)”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    There was a main effect of time on plasma 2AG concentrations across all time points and both sleep conditions (p<0.001), with lowest at 10 a.m. day 4 (2.04 ± 0.16 pmol/ml) and highest at 8:30 a.m. day 4 (3.10 ± 0.44 pmol/ml).

    “repeated measures ANOVA revealed a strong main effect of time on plasma concentrations of 2AG (p < 0.001, lowest concentration at 10 a.m. on day 4, 2.04 ± 0.16 pmol/ml; highest concentration at 8:30 a.m. on day 4, 3.10 ± 0.44 pmol/ml)”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    In the short sleep condition, subjects slept 3.97 ± 0.05 h, 4.07 ± 0.03 h, and 4.12 ± 0.02 h on nights 1-3.

    “In the short sleep condition (i.e., subjects had an sleep opportunity of 4.25 h each night), they slept in total 3.97 ± 0.05 h on the first night, 4.07 ± 0.03 h on the second night, and 4.12 ± 0.02 h on the third night (F(1,12) = 3495, p < 0.001 for the main effect of Sleep condition).”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim.

    Findingown data

    No correlations were found of subjective hunger and stress ratings with plasma endocannabinoid concentrations.

    “When considering individual ratios (i.e., individual values at each time points on day 4 in the short sleep condition were divided by corresponding time-matched individual values in the normal sleep condition, e.g.plasma concentration of 2AG at 8:30 a.m. in the short sleep condition was divided by plasma concentration of 2AG at 8:30 a.m. in the normal sleep condition), no correlations were found”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Participants in general felt more stressed in the normal sleep condition than in the short sleep condition (p=0.010 for Sleep condition), especially for ratings done after physical exercise (15 min and 4 h post-exercise).

    “Concerning stress, participants in general felt more stressed in the normal sleep condition than they did in the short sleep condition (F(2.26,33.95)= 0.95, p = 0.407 for Sleep condition*Time; F(1.0,15.0)= 8.57, p = 0.010 for Sleep condition; F(2.47,37.03)= 2.83, p = 0.061 for Time), especially for ratings done after the physical exercise task had been completed (i.e., 15 min post-exercise and 4 h”
    Quote in the paperNot a substantial claim
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    Findingown data

    This study observed an increase in plasma 2AG of about 44%, much greater than the 17% diurnal fluctuation.

    “While we observed an increase much greater (about 44%) than this observed diurnal fluctuation”
    Quote in the paperNot a substantial claim
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    Findingown data

    Partial sleep loss increased pre-exercise plasma concentrations of 2AG only at 8:30 a.m. but not at 10 a.m.

    “In light of our findings that partial sleep loss increased pre-exercise plasma concentrations of 2AG only at 8:30 a.m. but not at 10 a.m.”
    • Also stated in: § 4.3. Sleep loss increases hunger feelings: possible role of 2AG · plain
      “However, three nights of partial sleep loss increased plasma concentrations of 2AG only shortly after awakening in the present study (i.e., 8:30 a.m.)”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Acute sleep loss accentuates the brain's hedonic response to food.

    “Acute sleep loss increases food intake and ideal portion sizes (Hogenkamp et al., 2013;St-Onge et al., 2011), accentuates the brain's hedonic response to food (Benedict et al., 2012), and relatedly, impairs the ability to cognitively inhibit pre-potent responses to rewarding food stimuli (Cedernaes et al., 2014; topics reviewed in Cedernaes et al., 2015a).”
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    • cites Benedict et al., 2012 source

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    Premisecitation

    2AG is more linked to hedonic motivation for food whereas AEA is more involved in driving homeostatic eating.

    “In relation to the latter, recent findings suggest 2AG to be more linked to hedonic motivation for food whereas AEA seems to be more involved in driving homeostatic eating (Monteleone et al., 2016).”
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    • cites Monteleone et al., 2016

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    Premisecitation

    Endocannabinoids AEA and 2AG are endogenously produced lipids that are elevated in blood in response to psychological stress.

    “The endocannabinoids anandamide (AEA) and 2arachidonoylglycerol (2AG) are endogenously produced lipids that have been found, for instance, to be elevated in blood in response to psychological stress (Hill et al., 2009;Dlugos et al., 2012).”
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    • cites Hill et al., 2009 source

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    • cites Dlugos et al., 2012 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Acute sleep loss increases food intake and ideal portion sizes.

    “Acute sleep loss increases food intake and ideal portion sizes (Hogenkamp et al., 2013;St-Onge et al., 2011), accentuates the brain's hedonic response to food (Benedict et al., 2012), and relatedly, impairs the ability to cognitively inhibit pre-potent responses to rewarding food stimuli (Cedernaes et al., 2014; topics reviewed in Cedernaes et al., 2015a).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Hogenkamp et al., 2013 source

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    • cites St-Onge et al., 2011 source

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    Premisecitation

    Following binding to central nervous system receptors such as CB1, endocannabinoids reduce anxiety and increase food intake.

    “Following their binding to central nervous system receptors (e.g.CB1 receptors), endocannabinoids have been shown, e.g., to reduce anxiety (Marsicano et al., 2002;Lutz et al., 2015) and increase food intake (Di Marzo et al., 2001).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Marsicano et al., 2002 source

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    Premisecitation

    Acute sleep loss impairs the ability to cognitively inhibit pre-potent responses to rewarding food stimuli.

    “Acute sleep loss increases food intake and ideal portion sizes (Hogenkamp et al., 2013;St-Onge et al., 2011), accentuates the brain's hedonic response to food (Benedict et al., 2012), and relatedly, impairs the ability to cognitively inhibit pre-potent responses to rewarding food stimuli (Cedernaes et al., 2014; topics reviewed in Cedernaes et al., 2015a).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Cedernaes et al., 2014 source

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    • cites Cedernaes et al., 2015a

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    Premisecitation

    Plasma AEA concentrations are increased during and shortly after intense exercise (60 min at 55% followed by 30 min at 75% Wmax) in healthy trained male cyclists.

    “For instance, a recent study involving 11 healthy trained male cyclists found plasma AEA concentrations to be increased during and shortly after intense exercise (i.e., 60 min at 55% followed by 30 min at 75% W max ; Heyman et al., 2012).”
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    • cites Heyman et al., 2012 source

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    Premisecitation

    Treadmill running increases blood levels of AEA only at moderate versus low or high exercise intensity (70-85% of age-adjusted maximum heart rate).

    “In another study, treadmill running resulted in increased blood levels of AEA; however, only at moderate -versus low or high -exercise intensity (i.e., at 70-85% of age-adjusted maximum heart rate) (Raichlen et al., 2013).”
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    Premisecitation

    One hour of moderate intensity exercise increases plasma AEA concentrations in young males.

    “Finally, a study involving 24 young males demonstrated that 1 h of moderate intensity exercise increased plasma AEA concentrations.”
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    • cites Sparling et al., 2003 source

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    Premisecitation

    Acute sleep deprivation acutely alleviates symptoms of depression.

    “Moreover, similar to the anxiolytic effects of endocannabinoids, acute sleep deprivation has repeatedly been shown to acutely alleviate symptoms of depression (Wu et al., 1999).”
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    Premisecitation

    Plasma 2AG concentrations show a trend to increase following exercise but do not reach statistical significance.

    “In the same study, plasma 2AG concentrations showed a similar trend to increase following exercise, but failed to reach statistical significance (Sparling et al., 2003).”
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    Study design and conductown data

    The assay's intrabatch, intra-assay and inter-assay imprecision were 0.5-11.2%, 2.0-13.9% and 0.6-17.1% for all analytes at low and high level.

    “Intrabatch, intra-assay and inter-assay imprecision was, respectively, 0.5-11.2%,2.0-13.9%and 0.6-17.1% for all analytes at low and high level.”
    Quote in the paperNot a substantial claim
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    Study design and conductreasoning

    Plasma endocannabinoid samples from the same subject were processed in the same batch, with low and high level quality controls, to minimize analytical variability.

    “In order to minimize the analytical variability caused by this phenomenon, samples from the same subject were processed in the same batch, and each batch included two replicates of low and high level quality controls (QCs).”
    Quote in the paperSubstantial claim
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    Premisecitation

    Exercise-induced elevations of endocannabinoid levels have been proposed to account partially for anxiolytic, anti-nociceptive and neuroprotective properties of exercise.

    “Exerciseinduced elevations of endocannabinoid levels have been proposed to account partially for anxiolytic (Tantimonaco et al., 2014;Fuss et al., 2015), anti-nociceptive (Galdino et al., 2014) and neuroprotective (Hill et al., 2010a) properties of exercise, which are all responses that instead are affected in a negative direction by sleep loss (e.g.Roy-Byrne et al., 1986;Schuh-Hofer et al., 2013;”
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    • cites Tantimonaco et al., 2014 source

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    • cites Fuss et al., 2015 source

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    Study design and conductnone given

    The order of experimental conditions was randomized and counterbalanced across subjects.

    “The order of experimental conditions was randomized and counterbalanced across subjects (Fig. 1).”
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    Study design and conductcitation

    Sleep was measured by polysomnography and scored by an experienced scorer according to standard criteria.

    “Sleep was subsequently scored by an experienced scorer (J.E.B.) according to standard criteria (Silber et al., 2007).”
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    Premisenone given

    No study has yet investigated whether exercise-induced elevations of endocannabinoids are affected by short sleep duration.

    “To our best knowledge, no study has yet investigated whether exercise-induced elevations of endocannabinoids are affected by short sleep duration.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    Anxiolytic, anti-nociceptive and neuroprotective properties of exercise are affected in a negative direction by sleep loss.

    “Exerciseinduced elevations of endocannabinoid levels have been proposed to account partially for anxiolytic (Tantimonaco et al., 2014;Fuss et al., 2015), anti-nociceptive (Galdino et al., 2014) and neuroprotective (Hill et al., 2010a) properties of exercise, which are all responses that instead are affected in a negative direction by sleep loss (e.g.Roy-Byrne et al., 1986;Schuh-Hofer et al., 2013;”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Roy-Byrne et al., 1986 source

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    • cites Schuh-Hofer et al., 2013 source

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    • cites Cedernaes et al., 2016

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    Premisecitation

    One night of total sleep deprivation disrupted the normal pattern of circulating AEA, indicating significant dysregulation of circulating AEA.

    “this pattern was disrupted following one night of total sleep deprivation (e.g.concentrations of plasma AEA did not decline over the day), indicating that the absence of sleep produces a significant dysregulation of circulating AEA (Vaughn et al., 2010).”
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    • cites Vaughn et al., 2010 source

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    Premisecitation

    Total sleep loss did not alter circulating AEA concentrations.

    “others have reported that total sleep loss did not alter circulating AEA concentrations (Koethe et al., 2009)”
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    • cites Koethe et al., 2009 source

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    Interpretationown data

    The increase in plasma 2AG due to sleep restriction was transient, occurring shortly after awakening at 8:30 a.m. but no longer apparent at 10 a.m. on day 4.

    “The increase we observed in plasma 2AG due to sleep restriction was transient, as it occurred shortly after awakening at 8:30 a.m., but was no longer apparent at 10 a.m. on day 4.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Total sleep loss increased OEA levels in CSF but not in plasma.

    “whereas they instead found increased levels of OEA in CSF but not in plasma (Koethe et al., 2009).”
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    • cites Koethe et al., 2009 source

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    Premisecitation

    Similar effects (a rise in 2AG) have been found after acute psychological stress.

    “Similar effects have been found after acute psychological stress (Hill et al., 2009).”
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    • cites Hill et al., 2009 source

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    Premisecitation

    In a study of five healthy humans under a normal sleep-wake cycle, circulating AEA concentrations increased from nighttime to morning and then declined closer to nighttime.

    “in a study involving five healthy humans, circulating AEA concentrations increased from nighttime to morning and then declined again closer to nighttime when participants were kept under a normal sleep-wake cycle.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Vaughn et al., 2010 source

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    Premisecitation

    The increase of circulating endocannabinoids following exercise has been proposed to partially account for anxiolytic, anti-nociceptive, and neuroprotective properties of physical exercise.

    “The increase of circulating levels of endocannabinoids following exercise has been proposed to partially account for the anxiolytic (Tantimonaco et al., 2014), anti-nociceptive (Galdino et al., 2014) and neuroprotective (Hill et al., 2010a) properties of physical exercise.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Tantimonaco et al., 2014 source

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    • cites Galdino et al., 2014 source

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    • cites Hill et al., 2010a

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    Interpretationreasoning

    Sleep deprivation may have modulated post-exercise plasma concentrations of endocannabinoids before, in between, or after the time points measured (15 min and 4 h after exercise).

    “Importantly however, sleep deprivation may have modulated post-exercise plasma concentrations of endocannabinoids before, in between, or after, the time points measured in our study, i.e., 15 min and 4 h after exercise.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Differences in exercise intensity, circadian timing, blood sampling timing, and pre-exercise conditions could explain why this study observed an increase in 2AG but not AEA, whereas previous studies found the opposite.

    “Differences in exercise intensity, circadian timing of exercise, timing of blood sampling (i.e., during or different time points after exercise), and pre-exercise conditions (e.g.photic preload, time since last meal, macronutrient composition of last meal, and gender distribution) could offer possible explanations for why we observed an increase in plasma concentrations of 2AG but not AEA, whereas”
    Quote in the paperSubstantial claim
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    Premisecitation

    Studies using acute physical exercise as stressor found an increase of plasma AEA but not 2AG.

    “Studies utilizing acute physical exercise as stressor have however found different responses, i.e., an increase of plasma concentrations of AEA but not 2AG (Heyman et al., 2012;Raichlen et al., 2013;Sparling et al., 2003).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Heyman et al., 2012 source

      Not checked in the free run.

    • cites Raichlen et al., 2013 source

      Not checked in the free run.

    • cites Sparling et al., 2003 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    A previous study found plasma 2AG concentrations to increase by around 17% under resting conditions from 10 a.m. to 11 a.m.

    “a previous study found plasma 2AG concentrations to increase by around 17% under resting conditions from 10 a.m. to 11 a.m.(Hanlon et al., 2015)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Hanlon et al., 2015 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Recurrent partial sleep loss does not alter the centrally acting benefits of exercise.

    “Our results could therefore indirectly suggest that recurrent partial sleep loss does not alter these centrally acting benefits of exercise.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Plasma endocannabinoid concentrations reflect central endocannabinoid signaling relevant to behavioral effects such as hunger and mood.
    • Rests on an assumption: The exercise-induced rise in 2AG is representative of exercise-induced elevations of endocannabinoids generally.
    • Rests on an assumption: Findings in mice about CB1/CB2 receptors and running-induced anxiolysis/analgesia apply to humans.
  • Classified as probably not a substantial claim.

    Premisecitation

    In mice, central and peripheral CB1 and CB2 receptors are necessary for inducing anxiolysis and analgesia after running.

    “Indeed, recent research suggests that at least in mice, central and peripheral CB1 and CB2 receptors are necessary for inducing anxiolysis and analgesia after running (Fuss et al., 2015).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Fuss et al., 2015 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Differences in plasma endocannabinoid concentrations between sleep conditions might have occurred if exercise had been scheduled closer to awakening.

    “differences in plasma endocannabinoid concentrations between sleep conditions might have occurred if exercise would have been scheduled closer to awakening.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    Administration of 2AG into the shell of the nucleus accumbens increases food intake.

    “Furthermore, administration of 2AG into the shell of the nucleus accumbens, an extra-hypothalamic area strongly linked to eating motivation increases food intake (Kirkham et al., 2002).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kirkham et al., 2002 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    OEA activates PPAR-alpha, a major regulator of lipid metabolism activated to induce a metabolic adaptive response to prolonged fasting.

    “Since OEA has been shown to activate peroxisome proliferator-activated receptor alpha (PPAR-alpha) (Guzmán et al., 2004), a major regulator of lipid metabolism that is activated to induce a metabolic adaptive response to prolonged fasting (Kersten et al., 1999)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Guzmán et al., 2004 source

      Not checked in the free run.

    • cites Kersten et al., 1999 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Cannabinoids increase food craving and calorie intake.

    “A well-known effect of cannabinoids is increased food craving and calorie intake (Kirkham, 2009).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kirkham, 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The rise of OEA in plasma could stem from extended energy deprivation, exacerbated by the exercise intervention.

    “the rise of this lipid metabolite in plasma could also stem from extended energy deprivation, exacerbated by the exercise intervention.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The rise in plasma OEA at 4 h post-exercise could represent a circadian fluctuation rather than an exercise effect.

    “since this rise in plasma OEA occurred relatively late after physical exercise, this could also represent a circadian fluctuation, rather than an exercise effect”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Sleep restriction increases craving and intake of food during morning hours.

    “which have demonstrated that sleep restriction increases craving and intake of food during morning hours (Benedict et al., 2012;Cedernaes et al., 2014;Chapman et al., 2013;Hogenkamp et al., 2013;St-Onge et al., 2011)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Benedict et al., 2012 source

      Not checked in the free run.

    • cites Cedernaes et al., 2014 source

      Not checked in the free run.

    • cites Chapman et al., 2013 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Intraperitoneal administration of rimonabant reduces food intake and induces neuronal activation in hypothalamic nuclei involved in food intake regulation, such as the paraventricular nucleus.

    “For instance, intraperitoneal administration of rimonabant (an antagonist for the cannabinoid receptor CB 1 ) reduces food intake (Thornton-Jones et al., 2006) and induces neuronal activation in several hypothalamic nuclei involved in food intake regulation, such as the paraventricular nucleus (Verty et al., 2009).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Thornton-Jones et al., 2006 source

      Not checked in the free run.

    • cites Verty et al., 2009 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Acute sleep deprivation, foremost total sleep deprivation, has been shown to exert transient mood-improving effects.

    “acute sleep deprivation -foremost total sleep deprivation -has been shown to exert transient mood-improving effects (Wu et al., 1999).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wu et al., 1999

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Humans are more responsive to the effects of psychological stress when sleep-deprived compared to when well-rested.

    “For instance, there is some evidence that humans are more responsive to the effects of psychological stress when sleepdeprived compared to when they are well-rested (Cedernaes et al., 2015b;Minkel et al., 2014).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Cedernaes et al., 2015b

      Not checked in the free run.

    • cites Minkel et al., 2014 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The small but significant increase in plasma 2AG shortly after awakening may have mediated the subjective stress-reducing effects of short sleep duration.

    “it could be that the small but significant increase in plasma concentrations of 2AG shortly after awakening may have mediated the subjective stressreducing effects of short sleep duration.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Plasma endocannabinoid concentrations reflect central endocannabinoid signaling relevant to behavioral effects such as hunger and mood.
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Chronic sleep loss has been associated with increased psychological stress.

    “While chronic sleep loss has been associated with increased psychological stress (Akerstedt, 2006)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Akerstedt, 2006 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sleep restriction has been shown to promote adverse psychological symptoms.

    “Finally, sleep restriction has also been shown to promote adverse psychological symptoms (Roy-Byrne et al., 1986).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Roy-Byrne et al., 1986 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Chronic insufficient sleep is associated with elevated risk of long-term weight gain and obesity.

    “and possibly also a reason for the previously observed elevated risk of long term weight gain and obesity in those who chronically suffer from insufficient sleep (Cappuccio et al., 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cappuccio et al., 2008 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Low doses of CB1 agonists tend to be anxiolytic and high doses tend to increase aversion and anxiety-related behaviors.

    “Given that low doses of CB1 agonists tend to be anxiolytic and high doses tend to increase aversion and anxiety-related behaviors (Ganon-Elazar and Akirav, 2012; also reviewed in Viveros et al., 2005)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Ganon-Elazar and Akirav, 2012

      Not checked in the free run.

    • cites Viveros et al., 2005 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Activation of the endocannabinoid system has been previously shown to increase acutely appetite and mood.

    “Given that activation of the endocannabinoid system has been previously shown to increase acutely appetite and mood (Di Marzo et al., 2001;Lutz et al., 2015)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Di Marzo et al., 2001 source

      Not checked in the free run.

    • cites Lutz et al., 2015 source

      Not checked in the free run.

57 of 57
  • The paper relies on this without support.

    Endocannabinoids can readily cross the blood-brain barrier.

    “Due to their highly lipophilic properties, endocannabinoids can readily cross the blood-brain barrier.”
  • The paper relies on this without support.

    Plasma endocannabinoid concentrations reflect central endocannabinoid signaling relevant to behavioral effects such as hunger and mood.

    “Our results could therefore indirectly suggest that recurrent partial sleep loss does not alter these centrally acting benefits of exercise.”
    “our results could suggest that behavioral effects of acute sleep loss, such as increased hunger and transiently improved psychological state, may partially result from activation of this signaling pathway.”
  • The paper relies on this without support.

    The exercise-induced rise in 2AG is representative of exercise-induced elevations of endocannabinoids generally.

    “In contrast, exercise-induced elevations of endocannabinoids appear to be less affected by short sleep duration.”
    “An additional finding of the present study is that the exerciseinduced rise in plasma concentrations of 2AG did not differ between sleep conditions.”
  • The paper relies on this without support.

    Findings in mice about CB1/CB2 receptors and running-induced anxiolysis/analgesia apply to humans.

    “Indeed, recent research suggests that at least in mice, central and peripheral CB1 and CB2 receptors are necessary for inducing anxiolysis and analgesia after running (Fuss et al., 2015).”
    “Our results could therefore indirectly suggest that recurrent partial sleep loss does not alter these centrally acting benefits of exercise.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • ConsistentF(1, 12) = 3495reported p < .001 · recomputed p < .001

    “F(1,12) = 3495, p < .001”

  • ConsistentF(2.23, 33.22) = 2.55reported p = .088 · recomputed p = .088

    “F(2.23,33.22)= 2.55, p = .088”

  • ConsistentF(1, 15) = 0.04reported p = .843 · recomputed p = .844

    “F(1.0,15.0)= 0.04, p = .843”

  • ConsistentF(2.74, 41.08) = 14.94reported p < .001 · recomputed p < .001

    “F(2.74,41.08)= 14.94, p < .001”

  • ConsistentF(2.26, 33.95) = 0.95reported p = .407 · recomputed p = .406

    “F(2.26,33.95)= 0.95, p = .407”

  • ConsistentF(1, 15) = 8.57reported p = .01 · recomputed p = .010

    “F(1.0,15.0)= 8.57, p = .010”

  • ConsistentF(2.47, 37.03) = 2.83reported p = .061 · recomputed p = .061

    “F(2.47,37.03)= 2.83, p = .061”

7 of 7

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Self-check results appear here once an independent check has confirmed them.

Cites

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Authors
Cedernaes, J., Fanelli, F., Fazzini, A., Pagotto, U., Broman, J.-E., Vogel, H., Dickson, S. L., Schiöth, H. B., & Benedict, C.
Affiliations
  • Uppsala University (SE)
  • IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
  • German Institute of Human Nutrition (DE)
  • University of Gothenburg (SE)
Corresponding author
  • Cedernaes, Jonathan
  • Benedict, Christian
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2016-12
Volume
74
Pages
258-268
ISSN
0306-4530 (ISSN-L)
OpenAlex
W2522874465
Cited by
59
References
57
Citations by year
2026: 2 · 2025: 6 · 2024: 5 · 2023: 11 · 2022: 6 · 2021: 8 · 2020: 3 · 2019: 7 · 2018: 5 · 2017: 6
FWCI
4.86
Type
journal article
Language
en
Open access
Locations
  • Psychoneuroendocrinology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc-nd)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by-nc-nd)
Funders
  • AFA Försäkring (140006)
  • Erik, Karin and Gösta Selanders Foundation
  • Fredrik och Ingrid Thurings Stiftelse
  • Lars Hiertas Minne Foundation
  • Novo Nordisk Foundation
  • Tore Nilson Foundation
  • Swedish Research Society
  • Swedish Society for Medicine
  • Swedish Brain Foundation
  • Swedish Research Council
  • Åke Wiberg Foundation
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
Keywords
sleep restriction, sleep deprivation, endocannabinoids, 2-arachidonoylglycerol, acute exercise, hunger, appetite, subjective stress, sleep-wake cycle, endocannabinoid system, cycle ergometry
MeSH terms
Adult, Humans, Hunger, Male, Sleep, Sleep Deprivation, Stress, Psychological, Exercise, Young Adult, Endocannabinoids

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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