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Victoria Chapman - One of the best experts on this subject based on the ideXlab platform.

  • lack of effect of chronic pre treatment with the faah inhibitor urb597 on inflammatory pain behaviour evidence for plastic changes in the endocannabinoid system
    British Journal of Pharmacology, 2012
    Co-Authors: Bright N Okine, David A Kendall, David A Barrett, Annie Patel, Andrew J. Bennett, Stephen P.h. Alexander, Leonie M Norris, Stephen G. Woodhams, James J. Burston, Victoria Chapman
    Abstract:

    BACKGROUND AND PURPOSE Elevating levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to be a safer approach devoid of cannabinoid receptor-mediated side effects. Here, we have determined the effects of sustained pharmacological inhibition of FAAH on inflammatory pain behaviour and if pharmacological inhibition of FAAH was as effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH Effects of pre-treatment with a single dose, versus 4 day repeated dosing with the selective FAAH inhibitor, URB597 (i.p. 0.3 mg·kg−1), on carrageenan-induced inflammatory pain behaviour and spinal pro-inflammatory gene induction were determined in rats. Effects of pain induction and of the drug treatments on levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (PEA) and oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS Single, but not repeated, URB597 treatment significantly attenuated the development of inflammatory hyperalgesia (P < 0.001, vs. vehicle-treated animals). Neither mode of URB597 treatment altered levels of AEA, PEA and OEA in the hind paw, or carrageenan-induced paw oedema. Single URB597 treatment produced larger increases in AEA, PEA and OEA in the spinal cord, compared with those after repeated administration. Single and repeated URB597 treatment decreased levels of immunoreactive N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) in the spinal cord and attenuated carrageenan-induced spinal pro-inflammatory gene induction. CONCLUSION AND IMPLICATIONS Changes in the endocannabinoid system may contribute to the loss of analgesic effects following repeated administration of low dose URB597 in this model of inflammatory pain.

  • Lack of effect of chronic pre‐treatment with the FAAH inhibitor URB597 on inflammatory pain behaviour: evidence for plastic changes in the endocannabinoid system
    British Journal of Pharmacology, 2012
    Co-Authors: Bright N Okine, David A Kendall, David A Barrett, Annie Patel, Andrew J. Bennett, Stephen P.h. Alexander, Leonie M Norris, Stephen G. Woodhams, James J. Burston, Victoria Chapman
    Abstract:

    BACKGROUND AND PURPOSE Elevating levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to be a safer approach devoid of cannabinoid receptor-mediated side effects. Here, we have determined the effects of sustained pharmacological inhibition of FAAH on inflammatory pain behaviour and if pharmacological inhibition of FAAH was as effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH Effects of pre-treatment with a single dose, versus 4 day repeated dosing with the selective FAAH inhibitor, URB597 (i.p. 0.3 mg·kg−1), on carrageenan-induced inflammatory pain behaviour and spinal pro-inflammatory gene induction were determined in rats. Effects of pain induction and of the drug treatments on levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (PEA) and oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS Single, but not repeated, URB597 treatment significantly attenuated the development of inflammatory hyperalgesia (P < 0.001, vs. vehicle-treated animals). Neither mode of URB597 treatment altered levels of AEA, PEA and OEA in the hind paw, or carrageenan-induced paw oedema. Single URB597 treatment produced larger increases in AEA, PEA and OEA in the spinal cord, compared with those after repeated administration. Single and repeated URB597 treatment decreased levels of immunoreactive N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) in the spinal cord and attenuated carrageenan-induced spinal pro-inflammatory gene induction. CONCLUSION AND IMPLICATIONS Changes in the endocannabinoid system may contribute to the loss of analgesic effects following repeated administration of low dose URB597 in this model of inflammatory pain.

  • quantitative profiling of endocannabinoids and related compounds in rat brain using liquid chromatography tandem electrospray ionization mass spectrometry
    Analytical Biochemistry, 2007
    Co-Authors: Denise Richardson, David A Kendall, Victoria Chapman, Catharine A Ortori, David A Barrett
    Abstract:

    Abstract A sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method is described for the simultaneous identification and quantification of eight endocannabinoid (EC) or related “entourage” compounds in rat brain tissue. Analytes were extracted and purified from rat brain tissue using an ethyl acetate/hexane solvent extraction, followed by a solid phase extraction (SPE) protocol. Chromatographic separation was achieved using a gradient elution, with a mobile phase of acetonitrile, formic acid, and ammonium acetate, at pH 3.6. A Thermo Hypersil C8 HyPurity Advance column (100 × 2.1 mm i.d., 3 μm) was used with a flow rate of 0.3 ml/min). Anandamide (AEA), 2-arachidonyl glycerol (2-AG), 2-arachidonylglyceryl ether (noladin ether), O-arachidonyl ethanolamide (virodhamine), 2-linoleoyl glycerol (2-LG), arachidonyl glycine, oleoyl ethanolamide (OEA), and palmitoyl ethanolamide (PEA) were quantified by positive ion tandem electrospray ionization mass spectrometry. Internal standards were deuterated AEA, deuterated 2-AG, and heptadecanoyl ethanolamide (HEA). Linearity was proven over the range of 25 fmol to 250 pmol, with a limit of detection of 25 fmol on column for all analytes except 2-AG, noladin ether, and 2-LG (250 fmol). This corresponded to a limit of quantification in biological tissue of 10 pmol/g for all analytes except 2-AG (100 pmol/g). Intra- and interday precision in biological tissue was routinely approximately 20% or lower, and accuracy was between 65% and 155%. This method was used to quantitatively profile regional differences in nine discrete rat brain regions for AEA, 2-AG, 2-LG, OEA, PEA, noladin ether, virodhamine, and arachidonyl glycine.

Paola Vitaglione - One of the best experts on this subject based on the ideXlab platform.

  • Mediterranean diet consumption affects the endocannabinoid system in overweight and obese subjects: possible links with gut microbiome, insulin resistance and inflammation
    European Journal of Nutrition, 2021
    Co-Authors: Silvia Tagliamonte, Rosalia Ferracane, Manolo Laiola, Marilena Vitale, Maria A. Gallo, Victoria Meslier, Nicolas Pons, Danilo Ercolini, Paola Vitaglione
    Abstract:

    Purpose To investigate whether a Mediterranean diet (MD) affected the plasma concentrations of endocannabinoids (ECs), N-acylethanolamines (NAEs) and their specific ratios in subjects with lifestyle risk factors for metabolic diseases. To identify the relationship between circulating levels of these compounds and gut microbiome, insulin resistance and systemic inflammation. Methods A parallel 8-week randomised controlled trial was performed involving 82 overweight and obese subjects aged (mean ± SEM) 43 ± 1.4 years with a BMI of 31.1 ± 0.5 kg/m^2, habitual Western diet (CT) and sedentary lifestyle. Subjects were randomised to consume an MD tailored to their habitual energy and macronutrient intake ( n  = 43) or to maintain their habitual diet ( n  = 39). Endocannabinoids and endocannabinoid-like molecules, metabolic and inflammatory markers and gut microbiome were monitored over the study period. Results The MD intervention lowered plasma arachidonoylethanolamide (AEA, p  = 0.02), increased plasma oleoylethanolamide/palmitoylethanolamide (OEA/PEA, p  = 0.009) and OEA/AEA ( p  = 0.006) and increased faecal Akkermansia muciniphila ( p  = 0.026) independent of body weight changes. OEA/PEA positively correlated with abundance of key microbial players in diet–gut–health interplay and MD adherence. Following an MD, individuals with low-plasma OEA/PEA at baseline decreased homeostatic model assessment of insulin resistance index ( p  = 0.01), while individuals with high-plasma OEA/PEA decreased serum high-sensitive C-reactive protein ( p  = 0.02). Conclusions We demonstrated that a switch from a CT to an isocaloric MD affects the endocannabinoid system and increases A. muciniphila abundance in the gut independently of body weight changes. Endocannabinoid tone and microbiome functionality at baseline drives an individualised response to an MD in ameliorating insulin sensitivity and inflammation. Clinical Trial Registry number and website NCT03071718; www.clinicaltrials.gov

  • Endocannabinoids, endocannabinoid-like molecules and their precursors in human small intestinal lumen and plasma: does diet affect them?
    European Journal of Nutrition, 2020
    Co-Authors: Silvia Tagliamonte, Rosalia Ferracane, Chris I. R. Gill, L. Kirsty Pourshahidi, Mary M. Slevin, Ruth K. Price, Roger Lawther, Gloria O’connor, Paola Vitaglione
    Abstract:

    Purpose To determine the small intestinal concentration of endocannabinoids (ECs), N -acylethanolamines (NAEs) and their precursors N -acylphosphatidylethanolamines (NAPEs) in humans. To identify relationships between those concentrations and habitual diet composition as well as individual inflammatory status. Methods An observational study was performed involving 35 participants with an ileostomy (18W/17M, aged 18–70 years, BMI 17–40 kg/m^2). Overnight fasting samples of ileal fluid and plasma were collected and ECs, NAEs and NAPEs concentrations were determined by LC-HRMS. Dietary data were estimated from self-reported 4-day food diaries. Results Regarding ECs, N -arachidonoylethanolamide (AEA) was not detected in ileal fluids while 2-arachidonoylglycerol (2-AG) was identified in samples from two participants with a maximum concentration of 129.3 µg/mL. In contrast, mean plasma concentration of AEA was 2.1 ± 0.06 ng/mL and 2-AG was 4.9 ± 1.05 ng/mL. NAEs concentrations were in the range 0.72–17.6 µg/mL in ileal fluids and 0.014–0.039 µg/mL in plasma. NAPEs concentrations were in the range 0.3–71.5 µg/mL in ileal fluids and 0.19–1.24 µg/mL in plasma being more abundant in participants with obesity than normal weight and overweight. Significant correlations between the concentrations of AEA, OEA and LEA in biological fluids with habitual energy or fat intakes were identified. Plasma PEA positively correlated with serum C-reactive protein. Conclusion We quantified ECs, NAEs and NAPEs in the intestinal lumen. Fat and energy intake may influence plasma and intestinal concentrations of these compounds. The luminal concentrations reported would allow modulation of the homeostatic control of food intake via activation of GPR119 receptors located on the gastro-intestinal mucosa. Clinical trial registry number and website NCT04143139; www.clinicaltrials.gov .

  • N-Acylphosphatidylethanolamines and N-acylethanolamines increase in saliva upon food mastication: the influence of the individual nutritional status and fat type in food
    Food & function, 2020
    Co-Authors: Lucia De Luca, Rosalia Ferracane, Nancy Calderón Ramírez, Paola Vitaglione
    Abstract:

    This study aimed to evaluate the influence of the individual nutritional status on the salivary concentration of N-acylethanolamines (NAEs), including linoleoylethanolamide (LEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA), and their precursors N-acylphosphatidylethanolamines (NAPEs) upon mastication of biscuits containing different fats. Three types of biscuits were formulated with 10% extra-virgin olive oil (EVOB), 10% palm oil (PALMB) or 10% paraffin oil (0% lipids, CONB). Twenty-five healthy subjects, 12 normal weight (NW, 9 F, 30.4 ± 8.7 years) and 13 obese (OB, 8 F, 35.5 ± 10.7 years) participated in a randomized crossover study. Fasting subjects collected unstimulated saliva (US) and stimulated saliva by masticating a parafilm piece (PP), and CONB, EVOB and PALMB. NAPEs, LEA, OEA and PEA were quantified in saliva samples by liquid chromatography–high-resolution mass spectrometry. The results showed that salivary NAPE and NAE concentrations in OB were higher than in NW in both US (NAPEs: 280.0 ± 45.4 ng mL−1vs. 121.8 ± 24.4 ng mL−1, p = 0.015; NAEs: 10.8 ± 1.4 ng mL−1vs. 4.8 ± 0.8 ng mL−1, p = 0.002, respectively) and PP (NAPEs: 259.8 ± 47.1 ng mL−1vs. 121.7 ± 16.9 ng mL−1, p = 0.049; NAEs: 6.1 ± 0.8 ng mL−1vs. 3.8 ± 0.4 ng mL−1, p = 0.03, respectively). NAPE and LEA levels were similar in US and PP, while the levels of OEA and PEA were lower in PP vs. US. Compared to PP, biscuit mastication increased the salivary NAPEs, LEA, OEA and overall NAEs in NW and OB. NAPEs increased in the order of EVOB = CONB > PALMB in NW and EVOB > CONB = PALMB in OB. LEA, OEA and overall NAEs increased similarly with all the biscuits in NW and in the order of EVOB > PALMB > CONB in OB. In contrast, the PEA concentration did not vary in saliva upon biscuit mastication in NW and neither with EVOB in OB, while it lowered with CONB and PALMB in OB. In conclusion, OB showed higher salivary levels of NAPEs and NAEs than NW. Mastication itself did not vary salivary NAPEs and LEA but reduced OEA, PEA and overall NAEs. Biscuit mastication increased salivary NAPEs and all NAEs, but PEA. Altogether, the data suggested that NAPEs and NAEs were released in saliva from biscuits at levels influenced by the individual nutritional status and biscuit type. These findings may have implications in molecular mechanisms underpinning gustatory processes in humans.

David A Barrett - One of the best experts on this subject based on the ideXlab platform.

  • lack of effect of chronic pre treatment with the faah inhibitor urb597 on inflammatory pain behaviour evidence for plastic changes in the endocannabinoid system
    British Journal of Pharmacology, 2012
    Co-Authors: Bright N Okine, David A Kendall, David A Barrett, Annie Patel, Andrew J. Bennett, Stephen P.h. Alexander, Leonie M Norris, Stephen G. Woodhams, James J. Burston, Victoria Chapman
    Abstract:

    BACKGROUND AND PURPOSE Elevating levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to be a safer approach devoid of cannabinoid receptor-mediated side effects. Here, we have determined the effects of sustained pharmacological inhibition of FAAH on inflammatory pain behaviour and if pharmacological inhibition of FAAH was as effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH Effects of pre-treatment with a single dose, versus 4 day repeated dosing with the selective FAAH inhibitor, URB597 (i.p. 0.3 mg·kg−1), on carrageenan-induced inflammatory pain behaviour and spinal pro-inflammatory gene induction were determined in rats. Effects of pain induction and of the drug treatments on levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (PEA) and oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS Single, but not repeated, URB597 treatment significantly attenuated the development of inflammatory hyperalgesia (P < 0.001, vs. vehicle-treated animals). Neither mode of URB597 treatment altered levels of AEA, PEA and OEA in the hind paw, or carrageenan-induced paw oedema. Single URB597 treatment produced larger increases in AEA, PEA and OEA in the spinal cord, compared with those after repeated administration. Single and repeated URB597 treatment decreased levels of immunoreactive N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) in the spinal cord and attenuated carrageenan-induced spinal pro-inflammatory gene induction. CONCLUSION AND IMPLICATIONS Changes in the endocannabinoid system may contribute to the loss of analgesic effects following repeated administration of low dose URB597 in this model of inflammatory pain.

  • Lack of effect of chronic pre‐treatment with the FAAH inhibitor URB597 on inflammatory pain behaviour: evidence for plastic changes in the endocannabinoid system
    British Journal of Pharmacology, 2012
    Co-Authors: Bright N Okine, David A Kendall, David A Barrett, Annie Patel, Andrew J. Bennett, Stephen P.h. Alexander, Leonie M Norris, Stephen G. Woodhams, James J. Burston, Victoria Chapman
    Abstract:

    BACKGROUND AND PURPOSE Elevating levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to be a safer approach devoid of cannabinoid receptor-mediated side effects. Here, we have determined the effects of sustained pharmacological inhibition of FAAH on inflammatory pain behaviour and if pharmacological inhibition of FAAH was as effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH Effects of pre-treatment with a single dose, versus 4 day repeated dosing with the selective FAAH inhibitor, URB597 (i.p. 0.3 mg·kg−1), on carrageenan-induced inflammatory pain behaviour and spinal pro-inflammatory gene induction were determined in rats. Effects of pain induction and of the drug treatments on levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (PEA) and oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS Single, but not repeated, URB597 treatment significantly attenuated the development of inflammatory hyperalgesia (P < 0.001, vs. vehicle-treated animals). Neither mode of URB597 treatment altered levels of AEA, PEA and OEA in the hind paw, or carrageenan-induced paw oedema. Single URB597 treatment produced larger increases in AEA, PEA and OEA in the spinal cord, compared with those after repeated administration. Single and repeated URB597 treatment decreased levels of immunoreactive N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) in the spinal cord and attenuated carrageenan-induced spinal pro-inflammatory gene induction. CONCLUSION AND IMPLICATIONS Changes in the endocannabinoid system may contribute to the loss of analgesic effects following repeated administration of low dose URB597 in this model of inflammatory pain.

  • entourage effects of n palmitoylethanolamide and n oleoylethanolamide on vasorelaxation to anandamide occur through trpv1 receptors
    British Journal of Pharmacology, 2008
    Co-Authors: David A Barrett, Michael D Randall
    Abstract:

    Background and purpose: The endocannabinoid N-arachidonoylethanolamide (anandamide) is co-synthesized with other N-acylethanolamides, namely N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA), which have been shown to potentiate anandamide responses (so-called ‘entourage effects’) in non-vascular tissues. It remains unclear whether such interactions occur in the circulation. Experimental approach: In rat isolated small mesenteric arteries, the effects of PEA and OEA on relaxation to anandamide and tissue contents of the N-acylethanolamides were examined under myographic conditions. Key results: Anandamide-induced relaxation was potentiated by pretreatment with PEA (10 μM) or OEA (1 μM), or in combination. The potentiation by PEA and OEA was endothelium-independent and abolished by treatment with capsaicin (10 μM), which desensitizes the transient receptor potential vanilloid type 1 (TRPV1) receptor system, or by the TRPV1 receptor antagonist, N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791) (2 μM). It was also observed at molar ratios of anandamide and PEA (or OEA) similar to those found in mesenteric arteries. PEA and inhibition of anandamide hydrolysis by 3′-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate (URB597) (1 μM) additively potentiated anandamide responses. On the other hand, PEA and OEA also induced vasorelaxation per se (rank order of potency: anandamide>OEA>PEA), but relaxation to the three N-acylethanolamides displayed different sensitivity to treatment with capsaicin, SB366791 and URB597. For example, relaxations to anandamide and OEA, but not PEA, were attenuated by both capsaicin and SB366791. Conclusion and implications: This study shows that PEA and OEA potentiate relaxant responses to anandamide through TRPV1 receptors in rat small mesenteric arteries. The congeners also induce vasorelaxation per se, suggesting a function for the N-acylethanolamides in vascular control. British Journal of Pharmacology (2008) 155, 837–846; doi:10.1038/bjp.2008.324; published online 11 August 2008

  • quantitative profiling of endocannabinoids and related compounds in rat brain using liquid chromatography tandem electrospray ionization mass spectrometry
    Analytical Biochemistry, 2007
    Co-Authors: Denise Richardson, David A Kendall, Victoria Chapman, Catharine A Ortori, David A Barrett
    Abstract:

    Abstract A sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method is described for the simultaneous identification and quantification of eight endocannabinoid (EC) or related “entourage” compounds in rat brain tissue. Analytes were extracted and purified from rat brain tissue using an ethyl acetate/hexane solvent extraction, followed by a solid phase extraction (SPE) protocol. Chromatographic separation was achieved using a gradient elution, with a mobile phase of acetonitrile, formic acid, and ammonium acetate, at pH 3.6. A Thermo Hypersil C8 HyPurity Advance column (100 × 2.1 mm i.d., 3 μm) was used with a flow rate of 0.3 ml/min). Anandamide (AEA), 2-arachidonyl glycerol (2-AG), 2-arachidonylglyceryl ether (noladin ether), O-arachidonyl ethanolamide (virodhamine), 2-linoleoyl glycerol (2-LG), arachidonyl glycine, oleoyl ethanolamide (OEA), and palmitoyl ethanolamide (PEA) were quantified by positive ion tandem electrospray ionization mass spectrometry. Internal standards were deuterated AEA, deuterated 2-AG, and heptadecanoyl ethanolamide (HEA). Linearity was proven over the range of 25 fmol to 250 pmol, with a limit of detection of 25 fmol on column for all analytes except 2-AG, noladin ether, and 2-LG (250 fmol). This corresponded to a limit of quantification in biological tissue of 10 pmol/g for all analytes except 2-AG (100 pmol/g). Intra- and interday precision in biological tissue was routinely approximately 20% or lower, and accuracy was between 65% and 155%. This method was used to quantitatively profile regional differences in nine discrete rat brain regions for AEA, 2-AG, 2-LG, OEA, PEA, noladin ether, virodhamine, and arachidonyl glycine.

Cecilia J Hillard - One of the best experts on this subject based on the ideXlab platform.

  • endocannabinoids and related lipids in serum from patients with amyotrophic lateral sclerosis
    Muscle & Nerve, 2021
    Co-Authors: Gregory T Carter, Cecilia J Hillard, Ryan J Mclaughlin, Carrie Cuttler, Garrett Sauber, Douglas L Weeks, Michael D Weiss
    Abstract:

    Background The goals of this study were to determine whether serum concentrations of endocannabinoids (eCB) and related lipids predict disease status in patients with amyotrophic lateral sclerosis (ALS) relative to healthy controls, and whether concentrations correlate with disease duration and severity. Methods Serum concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA), and related lipids palmitoylethanolamine (PEA), oleoylethanolamine (OEA), and 2-oleoylglycerol (2-OG), were measured in samples from 47 patients with ALS and 19 healthy adults. Hierarchical binary logistic and linear regression analyses assessed whether lipid concentrations predicted disease status (ALS or healthy control), duration, or severity. Results Binary logistic regression revealed that, after controlling for age and gender, 2-AG, 2-OG and AEA concentrations were unique predictors of the presence of ALS, demonstrating odds ratios of 0.86 (P = .039), 1.03 (P = .023), and 42.17 (P = .026), respectively. When all five lipids and covariates (age, sex, race, ethnicity, body mass index, presence of a feeding tube) were included, the resulting model had an overall classification accuracy of 92.9%. Hierarchical linear regression analyses indicated that in patients with ALS, AEA and OEA inversely correlated with disease duration (P = .030 and .031 respectively), while PEA demonstrated a positive relationship with disease duration (P = .013). None of the lipids examined predicted disease severity. Conclusions These findings support previous studies indicating significant alterations in concentrations of circulating lipids in patients with ALS. They suggest that arachidonic and oleic acid containing small lipids may serve as biomarkers for identifying the presence and duration of this disease.

  • acute stress increases circulating anandamide and other n acylethanolamines in healthy humans
    Neuropsychopharmacology, 2012
    Co-Authors: Cecilia J Hillard, Andrea Dlugos, Emma Childs, Kara L Stuhr, Harriet De Wit
    Abstract:

    Stress plays an important role in psychiatric disorders, and preclinical evidence indicates that the central endocannabinoid system modulates endocrine and neuronal responses to stress. This study aimed to investigate the effect of acute stress on circulating concentrations of endocannabinoids (eCBs) in healthy humans. A total of 71 adults participated in two sessions in which they were exposed to either a standardized psychosocial stress procedure (Trier Social Stress Test) or a control task. Blood samples for eCB and cortisol assays and cardiovascular and subjective measures were obtained before and at regular intervals after the tasks. Serum concentrations of the eCBs, N-arachidonylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), as well as of the N-acylethanolamides (NAEs), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), and of the O-acylglycerol, 2-oleoylglycerol (2-OG), were determined. Compared with the control condition, stress increased serum concentrations of AEA and the other NAEs immediately after the stress period. Increases in PEA were positively correlated with increases in serum cortisol after stress. Furthermore, anxiety ratings at baseline were negatively correlated with baseline concentrations of AEA. The sex and menstrual cycle status of the subject affected the NAE responses to stress. Interestingly, subjects of Asian and African-American races exhibited different patterns of stress responses compared with the Caucasian subjects. These results indicate that stress increases circulating NAEs in healthy human volunteers. This finding supports a protective role for eCBs in anxiety. Further research is needed to elucidate the function of these lipid mediators, and to determine the mechanisms that regulate their appearance in the circulation.

  • circulating endocannabinoids and n acyl ethanolamines are differentially regulated in major depression and following exposure to social stress
    Psychoneuroendocrinology, 2009
    Co-Authors: Matthew N Hill, Gregory E Miller, Erica J Carrier, Boris B Gorzalka, Cecilia J Hillard
    Abstract:

    Central endocannabinoid signaling is known to be responsive to stressful stimuli; however, there is no research to date characterizing the effects of stress on peripheral endocannabinoid content. The current study examined serum content of the endocannabinoid ligands N-arachidonylethanolamide (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), and the non-cannabinoid N-acyl ethanolamine (NAE) molecules palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) under basal conditions, immediately following the Trier Social Stress Test (TSST), and 30 min thereafter, in 15 medication-free women diagnosed with major depression, and 15 healthy matched controls. Basal serum concentrations of AEA and 2-AG, but not PEA or OEA, were significantly reduced in women with major depression relative to matched controls, indicating a deficit in peripheral endocannabinoid activity. Immediately following the TSST, serum 2-AG concentrations were increased compared to baseline; serum AEA concentration was unchanged at this time point. Serum concentrations of PEA and OEA were significantly lower than baseline 30 min following the cessation of the TSST. The magnitude of these responses did not differ between depressed and control subjects. These are the first data to demonstrate that the peripheral endocannabinoid/NAE system is responsive to exposure to stress.

Thi Ai Diep - One of the best experts on this subject based on the ideXlab platform.

  • Acylethanolamines, anandamide and food intake
    Biochemical Pharmacology, 2009
    Co-Authors: Harald S. Hansen, Thi Ai Diep
    Abstract:

    Anandamide and the other acylethanolamines, . oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and linoleoylethanolamide (LEA), may be formed by several enzymatic pathways from their precursors, which are the -acylated ethanolamine phospholipids. The exact enzymatic pathways involved in their biosynthesis in specific tissues are not clarified. It has been suggested that endogenous anandamide could stimulate food intake by activation of cannabinoid receptors in the brain and/or in the intestinal tissue. On the other hand, endogenous OEA and PEA have been suggested to inhibit food intake by acting on receptors in the intestine. At present, there is no clear role for endogenous anandamide in controlling food intake via cannabinoid receptors, neither centrally nor in the gastrointestinal tract.

  • N-acylethanolamines, anandamide and food intake
    Biochemical pharmacology, 2009
    Co-Authors: Harald S. Hansen, Thi Ai Diep
    Abstract:

    Anandamide and the other N-acylethanolamines, e.g. oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and linoleoylethanolamide (LEA), may be formed by several enzymatic pathways from their precursors, which are the N-acylated ethanolamine phospholipids. The exact enzymatic pathways involved in their biosynthesis in specific tissues are not clarified. It has been suggested that endogenous anandamide could stimulate food intake by activation of cannabinoid receptors in the brain and/or in the intestinal tissue. On the other hand, endogenous OEA and PEA have been suggested to inhibit food intake by acting on receptors in the intestine. At present, there is no clear role for endogenous anandamide in controlling food intake via cannabinoid receptors, neither centrally nor in the gastrointestinal tract. However, OEA, PEA and perhaps also LEA may be involved in regulation of food intake by selective prolongation of feeding latency and post-meal interval. These N-acylethanolamines seem to be formed locally in the intestine, where they can activate PPARalpha located in close proximity to their site of synthesis. The rapid onset of OEA response and its reliance on an intact vagus nerve suggests that activation of PPARalpha does not result in formation of a transcription-dependent signal but must rely on an unidentified non-genomic signal that translates to activation of vagal afferents. Whether GPR119, TRPV1 and/or intestinal ceramide levels also contribute to the anorectic and weight-reducing effect of exogenous OEA is less clear. Prolonged intake of dietary fat (45 energy%) may promote over-consumption of food by decreasing the endogenous levels of OEA, PEA and LEA in the intestine.