Behavioral Pharmacological Examination of a Novel Buprenorphine Induction Method Among Individuals Who Use Fentanyl

Summary

The opioid overdose epidemic has persisted for several decades and is now further complicated by the permeation of fentanyl into the illicit opioid supply. While the effectiveness of medications to treat opioid use disorder (MOUD) have been well documented in the literature, the addition of fentanyl to the drug supply has complicated the initiation of MOUD, especially buprenorphine. Naloxone, an opioid antagonist, is currently utilized to reverse opioid overdose by displacing less-competitive ligands which bind at the mu-opioid receptor. Because induction to buprenorphine in the age of fentanyl is uncomfortable and can take several days to stabilize a patient on a therapeutic dose, the use of naloxone prior to buprenorphine can aid in a safe and rapid transition to buprenorphine treatment, without the effect of unintended prolonged precipitated withdrawal which can occur following the displacement of fentanyl by buprenorphine on the mu-opioid receptor. Therefore, this project will assess feasibility and acceptability of naloxone-facilitated buprenorphine initiation using a single-ascending dose design. The investigators will examine whether a single dose of buprenorphine is tolerated following administration of naloxone among a small group of individuals. If the dose is tolerated, the investigators will administer a larger dose among another small group of individuals. The investigators will examine the tolerability of up to 4 doses of buprenorphine following naloxone. This buprenorphine induction method has been characterized in case studies but it has not been evaluated in an empirical, systematic way in a controlled setting. This study will take place within an residential facility at Johns Hopkins Bayview Medical Campus, and will have immediate, real-world applicability in establishing a rapid, safe, and effective option to transition people with chronic fentanyl use to buprenorphine treatment.

Timeline

Start

2024-01-09

Primary completion

2026-01-01

Completion

2026-01-01

Publications

• Background Bergeria CL, Strain EC. Opioid Use Disorder: Pernicious and Persistent. Am J Psychiatry. 2022 Oct;179(10):708-714. doi: 10.1176/appi.ajp.20220699. No abstract available.
• Background Antoine D, Huhn AS, Strain EC, Turner G, Jardot J, Hammond AS, Dunn KE. Method for Successfully Inducting Individuals Who Use Illicit Fentanyl Onto Buprenorphine/Naloxone. Am J Addict. 2021 Jan;30(1):83-87. doi: 10.1111/ajad.13069. Epub 2020 Jun 23.
• Background Varshneya NB, Thakrar AP, Hobelmann JG, Dunn KE, Huhn AS. Evidence of Buprenorphine-precipitated Withdrawal in Persons Who Use Fentanyl. J Addict Med. 2022 Jul-Aug 01;16(4):e265-e268. doi: 10.1097/ADM.0000000000000922. Epub 2021 Nov 23.
• Background Randall A, Hull I, Martin SA. Enhancing Patient Choice: Using Self-administered Intranasal Naloxone for Novel Rapid Buprenorphine Initiation. J Addict Med. 2023 Mar-Apr 01;17(2):237-240. doi: 10.1097/ADM.0000000000001073. Epub 2022 Sep 22.
• Background Greenwald MK, Herring AA, Perrone J, Nelson LS, Azar P. A Neuropharmacological Model to Explain Buprenorphine Induction Challenges. Ann Emerg Med. 2022 Dec;80(6):509-524. doi: 10.1016/j.annemergmed.2022.05.032. Epub 2022 Aug 6.
• Background Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2004. Report No.: (SMA) 04-3939. Available from http://www.ncbi.nlm.nih.gov/books/NBK64245/
• Background Greenwald MK. Heroin craving and drug use in opioid-maintained volunteers: effects of methadone dose variations. Exp Clin Psychopharmacol. 2002 Feb;10(1):39-46. doi: 10.1037//1064-1297.10.1.39.
• Background Wong JSH, Nikoo M, Westenberg JN, Suen JG, Wong JYC, Krausz RM, Schutz CG, Vogel M, Sidhu JA, Moe J, Arishenkoff S, Griesdale D, Mathew N, Azar P. Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: protocol for an open-label, parallel-group, superiority, randomized controlled trial. Addict Sci Clin Pract. 2021 Feb 12;16(1):11. doi: 10.1186/s13722-021-00220-2.
• Background D'Onofrio G, Hawk KF, Perrone J, Walsh SL, Lofwall MR, Fiellin DA, Herring A. Incidence of Precipitated Withdrawal During a Multisite Emergency Department-Initiated Buprenorphine Clinical Trial in the Era of Fentanyl. JAMA Netw Open. 2023 Mar 1;6(3):e236108. doi: 10.1001/jamanetworkopen.2023.6108.

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