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Relationship between opioid cross-tolerance during buprenorphine stabilization and return to opioid use during buprenorphine dose tapering

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Abstract

Rationale

Opioid injection drug use (IDU) has been linked to a more severe pattern of use (e.g. tolerance, overdose risk) and shorter retention in treatment, which may undermine abstinence attempts.

Objectives

This secondary data analysis of four human laboratory studies investigated whether current opioid IDU modulates subjective abuse liability responses to high-dose hydromorphone during intermediate-dose buprenorphine stabilization (designed to suppress withdrawal but allow surmountable agonist effects), and whether hydromorphone response magnitude predicts latency of return to opioid use during buprenorphine dose-tapering.

Methods

Regular heroin users not currently seeking treatment (n = 54; 29 current injectors, 25 non-injectors) were stabilized on 8-mg/day sublingual buprenorphine and assessed for subjective responses (e.g. ‘liking’, craving) to hydromorphone 24-mg intramuscular challenge (administered 16-hr post-buprenorphine) under randomized, double-blinded, controlled conditions. A subgroup (n = 35) subsequently completed a standardized 3-week outpatient buprenorphine dose-taper, paired with opioid-abstinent contingent reinforcement, and were assessed for return to opioid use based on thrice-weekly urinalysis and self-report.

Results

During buprenorphine stabilization, IDU reported lower ‘liking’ of buprenorphine and post-hydromorphone peak ‘liking’, ‘good effect’ and ‘high’ compared to non-IDU. Less hydromorphone peak increase-from-baseline in ‘liking’ (which correlated with less hydromorphone-induced craving suppression) predicted significantly faster return to opioid use during buprenorphine dose-tapering.

Conclusions

In these buprenorphine-stabilized regular heroin users, IDU is associated with attenuated ‘liking’ response (more cross-tolerance) to buprenorphine and to high-dose hydromorphone challenge and, in turn, this cross-tolerance (but not IDU) predicts faster return to opioid use. Further research should examine mechanisms that link cross-tolerance to treatment response.

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Funding

NIH R01 DA015462 (MKG) from the National Institute on Drug Abuse, the Gertrude Levin Endowed Chair in Addiction and Pain Biology (MKG), the Michigan Department of Health and Human Services (Helene Lycaki/Joe Young, Sr. funds), and the Detroit Wayne Integrated Health Network supported this research. Funding sources had no role in the design or conduct of this study, nor in the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Neurosciences, School of Medicine, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Tolan Park Medical Building, 3901 Chrysler Service Drive, Suite 2A, Detroit, MI, 48201, USA

    Mark K. Greenwald

  2. Wayne State University, Detroit, MI, USA

    Tolani Sogbesan

  3. Wayne State University School of Medicine, Detroit, MI, USA

    Tabitha E.H. Moses

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  1. Mark K. Greenwald
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  2. Tolani Sogbesan
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Contributions

MKG oversaw all aspects of the project including conceptualization, data collection and management, analyses, and drafting/editing the manuscript. TS assisted with literature review, interpreting findings and drafting sections of the manuscript. TEHM assisted with initial study conceptualization and data analysis, and edited the manuscript.

Corresponding author

Correspondence to Mark K. Greenwald.

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conflicts of interest

MKG is a consultant for Indivior Inc., which makes buprenorphine products; however, Indivior played no role in this study. The authors declare no conflict of interest with respect to the conduct or content of this work.

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Greenwald, M.K., Sogbesan, T. & Moses, T.E. Relationship between opioid cross-tolerance during buprenorphine stabilization and return to opioid use during buprenorphine dose tapering. Psychopharmacology (2024). https://doi.org/10.1007/s00213-024-06549-1

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