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

Naunyn Schmiedebergs Arch Pharmacol. 2024 Jul;397(7):4511-4536. doi: 10.1007/s00210-023-02938-z. Epub 2024 Jan 27.

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.

Keywords: Animal model of depression; Antidepressant drugs; Depression; Early life stress; Endocannabinoid system.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidepressive Agents* / pharmacology
  • Antidepressive Agents* / therapeutic use
  • Depression / drug therapy
  • Depression / metabolism
  • Depressive Disorder, Major / drug therapy
  • Endocannabinoids* / metabolism
  • Humans

Substances

  • Endocannabinoids
  • Antidepressive Agents