Current and emerging pharmacotherapies for opioid dependence treatments in adults: a comprehensive update

ABSTRACT

Introduction

Opioid use disorder (OUD) is characterized by compulsive opioid seeking and taking, intense drug craving, and intake of opioids despite negative consequences. The prevalence of OUDs has now reached an all-time high, in parallel with peak rates of fatal opioid-related overdoses, where 15 million individuals worldwide meet the criteria for OUD. Further, in 2020, 120,000 opioid-related deaths were reported worldwide with over 75,000 of those deaths occurring within the United States.

Areas covered

In this review, we highlight pharmacotherapies utilized in patients with OUDs, including opioid replacement therapies, and opioid antagonists utilized for opioid overdoses and deterrent of opioid use. We also highlight newer treatments, such as those targeting the neuroimmune system, which are potential new directions for research given the recently established role of opioids in activating neuroinflammatory pathways, as well as over the counter remedies, including kratom, that may mitigate withdrawal.

Expert opinion

To effectively treat OUDs, a deeper understanding of the current therapeutics being utilized, their additive effects, and the added involvement of the neuroimmune system are essential. Additionally, a complete understanding of opioid-induced neuronal alterations and therapeutics that target these abnormalities – including the neuroimmune system – is required to develop effective treatments for OUDs.

KEYWORDS:

• Opioids
• opioid use disorder
• pharmacotherapies
• naloxone
• buprenorphine
• naltrexone
• methadone
• levo-alpha-acetyl-methadol
• kratom

Article highlights

• Opioid use disorder (OUD) impacts all parts of the world, with highest prevalence and number of fatal overdoses reported within the United States.

• Opioids elicit their rewarding effects by binding to opioid receptors across several brain regions and altering neuroimmune signaling, contributing to enhanced dopamine release in reward-related regions.

• Opioid replacement therapies (methadone and buprenorphine) are shown to be effective for decreasing opioid craving and relapse propensity.

• Targeting the neuroimmune pathways altered by opioids has shown promising preclinical efficacy and may prove beneficial for future treatment development.

• The use of medication assisted therapy and the collaborative care treatment model has emerged as a more effective treatment model than the traditional model of care, furthering treatment efficacy for OUD.

• Additional preclinical findings on the effects of pharmacotherapies and the neuroimmune system are essential to fully understand OUDs and effective treatments.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by National Institute of Health Grant Nos. F32AA027962, DA043172, and AA025590.