Peripheral endocannabinoids in major depressive disorder and alcohol use disorder: a systematic review.

Publication date: Aug 08, 2024

Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are two high-prevalent conditions where the Endocannabinoid system (ECS) is believed to play an important role. The ECS regulates how different neurotransmitters interact in both disorders, which is crucial for controlling emotions and responses to stress and reward stimuli. Measuring peripheral endocannabinoids (eCBs) in human serum and plasma can help overcome the limitations of detecting endocannabinoid levels in the brain. This systematic review aims to identify levels of peripheral eCBs in patients with MDD and/or AUD and find eCBs to use as diagnostic, prognostic biomarkers, and potential therapeutic targets. We conducted a systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines from the earliest manuscript until October 22, 2023, in three electronic databases. We included studies of human adults who had a current diagnosis of AUD and/or MDD and evaluated plasma or serum endocannabinoids. We carefully considered known variables that may affect endocannabinoid levels. We included 17 articles in this systematic review, which measured peripheral eCBs in 170 AUD and 359 MDD patients. Stressors increase peripheral 2-arachidonyl-glycerol (2-AG) concentrations, and 2-AG may be a particular feature of depression severity and chronicity. Anxiety symptoms are negatively correlated with anandamide (AEA) concentrations, and AEA significantly increases during early abstinence in AUD. Studies suggest a negative correlation between Oleoylethanolamide (OEA) and length of abstinence in AUD patients. They also show a significant negative correlation between peripheral levels of AEA and OEA and fatty acid amide hydrolase (FAAH) activity. Eicosapentaenoylethanolamide (EPEA) is correlated to clinical remission rates in depression. Included studies show known variables such as gender, chronicity, symptom severity, comorbid psychiatric symptoms, length of abstinence in the case of AUD, and stress-inducibility that can affect peripheral eCBs. This systematic review highlights the important role that the ECS plays in MDD and AUD. Peripheral eCBs appear to be useful biomarkers for these disorders, and further research may identify potential therapeutic targets. Using accessible biological samples such as blood in well-designed clinical studies is crucial to develop novel therapies for these disorders.

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Concepts Keywords
Crucial Alcohol use disorder
Databases Biomarkers
Depressive Endocannabinoids
Endocannabinoids Major depressive disorder

Semantics

Type Source Name
disease MESH major depressive disorder
disease MESH alcohol use disorder
drug DRUGBANK Glycerin
drug DRUGBANK Ethanol
disease MESH comorbidity
disease MESH neuroinflammation
disease MESH pathogenesis
disease MESH depressive disorders
drug DRUGBANK Dopamine
disease MESH schizophrenia
disease MESH bipolar disorder
disease MESH suicide
drug DRUGBANK Rimonabant
disease MESH obesity
drug DRUGBANK Indoleacetic acid
disease MESH Mental Disorders
disease MESH mood disorders
drug DRUGBANK Ethanolamine
drug DRUGBANK Prasterone
drug DRUGBANK Ethionamide
drug DRUGBANK Trestolone
drug DRUGBANK Escitalopram
disease MESH loneliness
disease MESH anhedonia
drug DRUGBANK Coenzyme M
drug DRUGBANK Icosapent
drug DRUGBANK Doconexent
drug DRUGBANK Esomeprazole
drug DRUGBANK Palmidrol
disease MESH inflammation
drug DRUGBANK Cocaine
disease MESH psychological stressors
drug DRUGBANK Serotonin
drug DRUGBANK Norepinephrine
drug DRUGBANK Citalopram
disease MESH cognitive decline
disease MESH PTSD
pathway KEGG Peroxisome
disease MESH migraine
drug DRUGBANK Testosterone
drug DRUGBANK Medical Cannabis
disease MESH Hepatitis
disease MESH anxiety disorders
disease MESH Dual diagnosis
disease MESH heroin dependence
drug DRUGBANK Corticotropin
drug DRUGBANK Diethylstilbestrol
disease MESH weight loss
drug DRUGBANK Ranitidine
pathway KEGG Alcoholism
drug DRUGBANK L-Aspartic Acid
drug DRUGBANK Natural alpha interferon
drug DRUGBANK Hydrocortisone
disease MESH morbidity
disease MESH Fibromyalgia
drug DRUGBANK Serine
disease MESH Psychological Distress
drug DRUGBANK Fish oil
drug DRUGBANK Isoxaflutole
disease MESH endometriosis
drug DRUGBANK Estradiol
drug DRUGBANK Dronabinol
pathway KEGG Circadian rhythm

Original Article

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