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How depression and antidepressant drugs affect endocannabinoid system?—review of clinical and preclinical studies

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Abstract

As major depressive disorder is becoming a more and more common issue in modern society, it is crucial to discover new possible grip points for its diagnosis and antidepressive therapy. One of them is endocannabinoid system, which has been proposed as a manager of emotional homeostasis, and thus, endocannabinoid alterations have been found in animals undergoing various preclinical models of depression procedures as well as in humans suffering from depressive-like disorders. In this review article, studies regarding those alterations have been summed up and analyzed. Another important issue raised by the researchers is the impact of currently used antidepressive drugs on endocannabinoid system so that it would be possible to predict reversibility of endocannabinoid alterations following stress exposure and, in the future, to be able to design individually personalized therapies. Preclinical studies investigating this topic have been analyzed and described in this article. Unfortunately, too few clinical studies in this field exist, what indicates an urgent need for collecting such data, so that it would be possible to compare them with preclinical outcomes and draw reliable conclusions.

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Abbreviations

ECS:

Endocannabinoid system

Δ9 :

-THC

Δ9-Tetrahydrocannabinol

CB1R:

Cannabinoid receptor type 1

CB2R:

Cannabinoid receptor type 2

AEA:

Anandamide

2-AG:

2-Arachidonoylglycerol

NAPE:

I-acyl-phosphatidylethanolamine

NAPE-PLD:

NAPE-specific phospholipase D

FAAH:

Fatty acid amide hydrolase

DAG:

Diacylglycerol

DAGLα:

Diacylglycerol lipase α

DAGLβ:

Diacylglycerol lipase β

MAGL:

Monoacylglycerol lipase

NAEs:

N-acylethanolamines

PEA:

N-palmitoylethanolamide

OEA:

N-oleoylethanolamide

SEA:

N-stearoylethanolamide

2-PG:

2-Palmitoylglycerol

2-OG:

2-Oleoylglycerol

AS:

Alcoholics who committed suicide

CA:

Chronic alcoholics

DLPFC:

Dorsolateral prefrontal cortex

PFC:

Prefrontal cortex

OBX:

Olfactory bulbectomy

PrL:

Prelimbic cortex

MO:

Medial orbital cortex

BLA:

Basolateral amygdala

DG:

Dentate gyrus

CPu:

Caudate-putamen, or striatum

NAc:

Nucleus accumbens

CA3:

Hippocampal region CA3

CeA:

Central amygdaloid nucleus

IMI:

Imipramine

TIA:

Tianeptine

ESC:

Escitalopram

FLUO:

Fluoxetine

TCP:

Trancylopramine

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Authors

Contributions

Jonasz Dragon: conceptualization, formal analysis, visualization, investigation, and writing—original draft. Ewa Obuchowicz: conceptualization, supervision, and writing—review and editing. The authors confirm that no paper mill and artificial intelligence was  used.

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Correspondence to Jonasz Dragon.

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The authors declare no competing interests.

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Dragon, J., Obuchowicz, E. How depression and antidepressant drugs affect endocannabinoid system?—review of clinical and preclinical studies. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-023-02938-z

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  • DOI: https://doi.org/10.1007/s00210-023-02938-z

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