Alterations of Stress-Related Glucocorticoids and Endocannabinoids in Hair of Chronic Cocaine Users

Voegel, Clarissa D.; Kroll, Sara L.; Schmid, Marc W.; Kexel, Ann-Kathrin; Baumgartner, Markus R.; Kræmer, Thomas; Binz, Tina M.; Quednow, Boris B.

doi:10.1093/ijnp/pyab070

Cited by 15 publications

(11 citation statements)

References 90 publications

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“…We recently reported lower tonic OEA and PEA hair concentration in a subgroup of the present chronic CU compared to healthy controls, specifically pronounced in individuals showing cocaine dependence [54]. However, we did not find differences between groups in AEA and 2-AG hair concentrations.…”

Section: Discussioncontrasting

confidence: 83%

“…Additionally, we used previously reported PET data of mGluR5 density of a subsample [50] to investigate potential cocaine-related associations between plasma eCB/NAE levels and mGluR5 density in an exploratory analysis. Based on reported animal model data and our recent findings [54], we expected alterations of eCB/NAE plasma levels primarily in dependent CU compared to controls, specifically for 2-AG, as well as an association between 2-AG and mGluR5 density in chronic CU.…”

Section: Introductionmentioning

confidence: 84%

“…Of note, reduced 2-AG levels in CUD was likely primarily driven by co-morbid alcohol use disorder (AUD) [53]. Moreover, we recently found lower levels of OEA and PEA, two NAEs that are linked to the metabolic pathway of AEA but do not bind directly at the CB 1 receptor, in hair samples of chronic CU compared to stimulantnaïve healthy controls [54]. Given that hair analysis enables a retrospective determination of eCB/NAE concentrations over the last three months on average [55], our previous findings indicate tonic alterations in these lipid pathways in chronic CU.…”

Section: Introductionmentioning

confidence: 94%

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Plasma endocannabinoids in cocaine dependence and their interaction with cocaine craving and metabotropic glutamate receptor 5 density in the human brain

Kroll

Hulka

Kexel

et al. 2023

Preprint

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Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N=103; 69 recreational CU and 34 dependent CU) and stimulant-naive healthy controls (N=92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N=33; controls: N=43). In an additional analysis using 11C-ABP688 positron emission tomography (PET) in a male subsample (CU: N=18; controls: N=16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence.

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Section: Discussioncontrasting

confidence: 83%

Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 94%

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Plasma endocannabinoids in cocaine dependence and their interaction with cocaine craving and metabotropic glutamate receptor 5 density in the human brain

Kroll

Hulka

Kexel

et al. 2023

Preprint

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“…No significant differences in AEA and 2-AG concentrations were found among the studied groups. Based on these results, the HPA axis and ECS appear to be critical regulators for cocaine use disorders [164].…”

Section: Gene and Protein Function/expression Changes Of Ecs Componentsmentioning

confidence: 94%

“…Hair samples LC-MS/MS Cortisone, cortisol, 2-AG, AEA, OEA, and PEA ↑Cortisone in recreational cocaine users and cocaine dependent users ↓OEA ↓PEA in cocaine dependent users compared to recreational cocaine users and controls No significant differences AEA and 2-AG levels [164] AA: African-American; AEA: anandamide; Amy: amygdala; CB1R/CNR1: cannabinoid receptor 1 (protein/gene); CB2R/CNR2: cannabinoid receptor 2 (protein/gene); DAGLα: Diacylglycerol lipase-alpha; DAGLβ: Diacylglycerol lipase-beta; D1-MSNs: medial spiny neurons expressing dopamine D1 receptors; D2-MSNs: medial spiny neurons expressing dopamine D2 receptors; ECS: endogenous cannabinoid system; EA: European-American; FAAH: fatty acid amidohydrolase; F344: Fisher 344 rats; Hipp: hippocampus; IHC: Immunohistochemistry; i.p. : intraperitoneal; ISH: in situ hybridization; LC-MS: Liquid chromatography-mass spectrometry; LC-MS/MS: liquid chromatography-tandem mass spectrometry; LSN: lateral septal nuclei; MAGL/MGLL: monoacylglycerol lipase (protein/gene); MDD: Major Depression Disorder; MDMA: 3,4-methylenedioxymethamphetamine; METH: methamphetamine; NAcc: nucleus accumbens; NAPE-PLD: N-acyl phosphatidylethanolamine phospholipase D; OEA: oleoylethanolamide; PEA: palmitoyl ethanolamide; PFC: prefrontal cortex (BA9: Brodmann's area 9); qPCR: quantitative real time PCR; SNP: single nucleotide polymorphism; STR: striatum; VTA: ventral tegmental area; WB: Western blot; 2-AG: 2-araquidonoyl glycerol; ↑: increase; ↓: decrease.…”

Section: Gene Polymorphisms Of Ecs Componentsmentioning

confidence: 97%

Biomarkers of the Endocannabinoid System in Substance Use Disorders

et al. 2022

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Despite substance use disorders (SUD) being one of the leading causes of disability and mortality globally, available therapeutic approaches remain ineffective. The difficulty in accurately characterizing the neurobiological mechanisms involved with a purely qualitative diagnosis is an obstacle to improving the classification and treatment of SUD. In this regard, identifying central and peripheral biomarkers is essential to diagnosing the severity of drug dependence, monitoring therapeutic efficacy, predicting treatment response, and enhancing the development of safer and more effective pharmacological tools. In recent years, the crucial role that the endocannabinoid system (ECS) plays in regulating the reinforcing and motivational properties of drugs of abuse has been described. This has led to studies characterizing ECS alterations after exposure to various substances to identify biomarkers with potential diagnostic, prognostic, or therapeutic utility. This review aims to compile the primary evidence available from rodent and clinical studies on how the ECS components are modified in the context of different substance-related disorders, gathering data from genetic, molecular, functional, and neuroimaging experimental approaches. Finally, this report concludes that additional translational research is needed to further characterize the modifications of the ECS in the context of SUD, and their potential usefulness in the necessary search for biomarkers.

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Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease

von Werdt,

Binz,

O’Gorman

et al. 2024

JAMA Netw Open

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ImportanceInfants with complex congenital heart disease (cCHD) may experience prolonged and severe stress when undergoing open heart surgery. However, little is known about long-term stress and its role in neurodevelopmental impairments in this population.ObjectiveTo investigate potential differences between early adolescents aged 10 to 15 years with cCHD and healthy controls in physiological stress markers by hair analysis, executive function (EF) performance, and resilience.Design, Setting, and ParticipantsThis single-center, population-based case-control study was conducted at the University Children’s Hospital Zurich, Switzerland. Patients with different types of cCHD who underwent cardiopulmonary bypass surgery during the first year of life and who did not have a genetic disorder were included in a prospective cohort study between 2004 and 2012. A total of 178 patients were eligible for assessment at ages 10 to 15 years. A control group of healthy term-born individuals was cross-sectionally recruited. Data assessment was between 2019 and 2021. Statistical analysis was performed from January to April 2023.ExposurePatients with cCHD who underwent infant open heart surgery.Main Outcomes and MeasuresPhysiological stress markers were quantified by summing cortisol and cortisone concentrations measured with liquid chromatography with tandem mass spectrometry in a 3-centimeter hair strand. EFs were assessed with a neuropsychological test battery to produce an age-adjusted EF summary score. Resilience was assessed with a standardized self-report questionnaire.ResultsThe study included 100 patients with cCHD and 104 controls between 10 and 15 years of age (mean [SD] age, 13.3 [1.3] years); 110 (53.9%) were male and 94 (46.1%) were female. When adjusting for age, sex, and parental education, patients had significantly higher sums of hair cortisol and cortisone concentrations (β, 0.28 [95% CI, 0.12 to 0.43]; P &lt; .001) and lower EF scores (β, −0.36 [95% CI, −0.49 to −0.23]; P &lt; .001) than controls. There was no group difference in self-reported resilience (β, −0.04 [95% CI, −0.23 to 0.12]; P = .63). A significant interaction effect between stress markers and EFs was found, indicating a stronger negative association in patients than controls (β, −0.65 [95% CI, −1.15 to −0.15]; P = .01). The contrast effects were not significant in patients (β, −0.21 [95% CI, −0.43 to −0.00]; P = .06) and controls (β, 0.09 [95% CI, −0.11 to 0.30]; P = .38).Conclusions and RelevanceThis case-control study provides evidence for altered physiological stress levels in adolescents with cCHD and an association with poorer EF. These results suggest that future studies are needed to better understand the neurobiological mechanisms and timing of alterations in the stress system and its role in neurodevelopment.

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Alterations of Stress-Related Glucocorticoids and Endocannabinoids in Hair of Chronic Cocaine Users

Cited by 15 publications

References 90 publications

Plasma endocannabinoids in cocaine dependence and their interaction with cocaine craving and metabotropic glutamate receptor 5 density in the human brain

Plasma endocannabinoids in cocaine dependence and their interaction with cocaine craving and metabotropic glutamate receptor 5 density in the human brain

Biomarkers of the Endocannabinoid System in Substance Use Disorders

Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease

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