Endogenous opioid system dysregulation in depression: implications for new therapeutic approaches

Marta Peciña, Jordan F. Karp, Sanjay Mathew, Mark S. Todtenkopf, Elliot W. Ehrich, Jon Kar Zubieta

Research output: Contribution to journalReview articlepeer-review

112 Scopus citations


The United States is in the midst of an opioid addiction and overdose crisis precipitated and exacerbated by use of prescription opioid medicines. The majority of opioid prescriptions are dispensed to patients with comorbid mood disorders including major depressive disorder (MDD). A growing body of research indicates that the endogenous opioid system is directly involved in the regulation of mood and is dysregulated in MDD. This involvement of the endogenous opioid system may underlie the disproportionate use of opioids among patients with mood disorders. Emerging approaches to address endogenous opioid dysregulation in MDD may yield novel therapeutics that have a low or absent risk of abuse and addiction relative to µ-opioid agonists. Moreover, agents targeting the endogenous opioid system would be expected to yield clinical benefits qualitatively different from conventional monaminergic antidepressants. The development of safe and effective agents to treat MDD-associated endogenous opioid dysregulation may represent a distinct and currently underappreciated means of addressing treatment resistant depression with the potential to attenuate the on-going opioid crisis.

Original languageEnglish (US)
Pages (from-to)576-587
Number of pages12
JournalMolecular Psychiatry
Issue number4
StatePublished - Apr 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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