Opioid Use Disorder Treatment Gaps and Emerging Therapeutics to Address Them

Area of Science:

• Pharmacology
• Neuroscience
• Addiction Medicine

Background:

• The opioid crisis persists despite existing medications for opioid use disorder (OUD).
• Current OUD treatments (methadone, buprenorphine, naltrexone) are selected based on patient opioid dependence levels.
• There is a critical need for novel OUD medications to fill existing treatment gaps.

Purpose of the Study:

• To review preclinical research for novel opioid use disorder (OUD) medications.
• To highlight candidate OUD medication targets.
• To propose future research directions for OUD medication development.

Main Methods:

• Review of preclinical research on OUD medication targets.
• Categorization of candidate medications targeting opioid distribution, mu-opioid receptors (MORs), and post-MOR signaling.
• Discussion of preclinical-to-clinical translation factors.

Main Results:

• Candidate OUD medications target opioid pharmacokinetics (vaccines, antibodies), MORs (low-efficacy agonists, long-acting formulations), and post-MOR signaling (GLP-1 agonists, D3 ligands).
• Research is exploring diverse strategies beyond traditional MOR agonism/antagonism.
• The evolving illicit opioid landscape necessitates innovative treatment approaches.

Conclusions:

• Continued research into novel OUD medication targets is essential.
• Developing safer and more effective treatments is crucial for public health.
• Future directions must consider ultrapotent opioids and non-opioid adulterants in the illicit drug supply.