Plasma concentrations of oleoylethanolamide and other acylethanolamides are altered in alcohol-dependent patients: effect of length of abstinence

Abstract

Acylethanolamides are a family of endogenous lipid mediators that are involved in physiological and behavioral processes associated with addiction. Recently, oleoylethanolamide (OEA) has been reported to reduce alcohol intake and relapse in rodents but the contribution of OEA and other acylethanolamides in alcohol addiction in humans is unknown. The present study is aimed to characterize the plasma acylethanolamides in alcohol dependence. Seventy-nine abstinent alcohol-dependent subjects (27 women) recruited from outpatient treatment programs and age-/sex-/body mass-matched healthy volunteers (28 women) were clinically assessed with the diagnostic interview PRISM according to the DSM-IV-TR after blood extraction for quantification of acylethanolamide concentrations in the plasma. Our results indicate that all acylethanolamides were significantly increased in alcohol-dependent patients compared with control subjects (p < 0.001). A logistic model based on these acylethanolamides was developed to distinguish alcohol-dependent patients from controls and included OEA, arachidonoylethanolamide (AEA) and docosatetraenoylethanolamide (DEA), providing a high discriminatory power according to area under the curve [AUC = 0.92 (95%CI: 0.87-0.96), p < 0.001]. Additionally, we found a significant effect of the duration of alcohol abstinence on the concentrations of OEA, AEA and DEA using a regression model (p < 0.05, p < 0.01 and p < 0.001, respectively), which was confirmed by a negative correlation (rho = -0.31, -0.40 and -0.44, respectively). However, acylethanolamides were not influenced by the addiction alcohol severity, duration of problematic alcohol use or diagnosis of psychiatric comorbidity. Our results support the preclinical studies and suggest that OEA, AEA and DEA are altered in alcohol-dependence during abstinence and that might act as potential markers for predicting length of alcohol abstinence.

Higher Impulsivity As a Distinctive Trait of Severe Cocaine Addiction among Individuals Treated for Cocaine or Alcohol Use Disorders

“…This one-dimensional score is in agreement with DSM-5 criteria [for more details, see Ref. ( 9 , 19 , 20 , 37 )]. For mental comorbidity associated with substance use disorders, we evaluated mood, anxiety, psychotic, eating, personality (borderline and antisocial personality disorders), and early-onset disorders in childhood [conduct disorder and attention deficit hyperactivity disorder (ADHD)].…”

“…Currently, a growing body of clinical studies in addicted populations is focused on identifying potential biomarkers related to substance use disorders (addiction severity, psychiatric comorbidity, etc.) and improving the stratification of patients for the use of appropriate behavioral and pharmacological therapies ( 19 , 20 , 31 ).…”

Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats

“…Here, we observed no changes in hepatic and plasma triglycerides 2 weeks after alcohol exposure but there was lower PPARα expression including mRNA and protein. Recently, we have demonstrated that circulating levels of N-oleoylethanolamine (OEA) are altered in rodents exposed to alcohol and abstinent patients [ 45 , 46 ]. This N-acylethanolamine is a natural ligand for PPARα and a short abstinence from alcohol induces increased OEA levels in the plasma [ 46 ], which may induce a down-regulation of PPARα.…”

“…The high expression of CB 2 and NAPE-PLD in the spleen of female rats exposed to adolescent intermittent alcohol may be compatible with increased endocannabinoid N-acylethanolamines (e.g., AEA). Further, we have reported high plasma N-acylethanolamine levels in alcohol-addicted patients during abstinence [ 46 ], but this observation has to be cautiously considered because of the experimental differences. Following this rationale, high levels of N-acylethanolamines may be linked to low plasma concentrations of TNF-α and IL-6, which is in accordance with previous in vitro studies that demonstrate that an increase in the AEA tone, either directly or indirectly through its biosynthesis/degradation enzymes, induces a decrease in the release of pro-inflammatory cytokines [ 52 , 53 , 54 ].…”

Potential association of plasma lysophosphatidic acid (LPA) species with cognitive impairment in abstinent alcohol use disorders outpatients

“…The total score was obtained from 0 to 18 evaluating the respectively subdomains: prehension, go-no-go, conflicting, Luria motor and lexical fluency; a cut-off point less than 16 separate normal from mild dysexecutive deficits, and a cut-off point less than 13 separate mild and severe dysexecutive Collection of plasma samples. Plasma sample collection was based on previous studies about lipid mediators in addiction and comorbid disorders 41 . Blood samples were obtained in the morning after fasting for 8-12 h (prior to the psychiatric interviews) by experienced nurses.…”