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Opioid use disorders (OUD) and opioid-related fatal overdoses are a significant public health concern in the United States and worldwide. To offer more effective medical interventions to treat or prevent OUD, anti-opioid vaccines are in development that reduce the distribution of the targeted opioids to brain and subsequently reduce the associated behavioral and toxic effects. Of critical importance is that anti-opioid vaccines should not interfere with medications to treat OUD. Hence, this study tested the pre-clinical proof of concept of combining a candidate oxycodone vaccine (OXY-KLH) with an FDA-approved extended-release naltrexone depot formulation (XR-NTX) in rats. The effects of XR-NTX on oxycodone-induced motor activity and antinociception were first assessed in non-vaccinated naïve rats to establish a baseline for subsequent studies. Next, OXY-KLH and XR-NTX were co-administered to determine whether the combination would affect the efficacy of each individual treatment and found that the combination of OXY-KLH and XR-NTX offered greater efficacy in reducing oxycodone-induced motor activity, thigmotaxis, antinociception, and respiratory depression over a range of repeated or escalating oxycodone doses in rats. These data support the feasibility of combining antibody-based therapies with opioid receptor antagonists to provide greater or prolonged protection against opioid-related toxicity or overdose. Combining anti-opioid vaccines with XR-NTX may provide prophylactic measures to subjects at risk of relapse, and accidental or deliberate exposure. Combination therapy may extend to other biologics (e.g., monoclonal antibodies) and medications against substance use disorders.

the journal of pharmacology and experimental therapeutics/the journal of pharmacology and experimental therapeutics

Combining a Candidate Vaccine for Opioid Use Disorders with Extended-Release Naltrexone Increases Protection against Oxycodone-Induced Behavioral Effects and Toxicity