Cited by 283Opioid Use Disorder TreatmentPain Management and Opioid UseNeuropeptides and Animal Physiology

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Acute administration of buprenorphine in humans: partial agonist and blockade effects.

Walsh, S L, Preston, K L, Bigelow, G E, Stitzer, M L·1995·The Journal of Pharmacology and Experimental Therapeutics

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Abstract

Buprenorphine, a mixed opioid agonist-antagonist, is being investigated as a treatment for opioid dependence. This study compared the acute subjective and physiological effects of sublingual buprenorphine to those of p.o. methadone over a wide range of doses and compared the ability of both drugs to alter the effects of an opioid challenge. Male inpatient volunteers (n = 9) with histories of opioid abuse participated in this double-blind, double-dummy study. Sublingual buprenorphine (0, 0.5, 2, 8, 16 and 32 mg) and p.o. methadone (3.75, 15 and 60 mg) were administered once weekly according to a Latin-square design, and subjects were monitored on a variety of physiological and subjective measures. Twenty-four hours later, subjects were tested with ascending doses of i.m. hydromorphone (0, 1 and 4 mg) given 45 min apart. Buprenorphine and methadone produced typical opioid agonist effects of long duration, including pupillary constriction, respiratory depression and elevations on subject-rated and observer-rated indices of euphoria, sedation and opioid-like symptoms. The buprenorphine dose-effect curves were nonlinear and maximal effects for most physiological and subjective measures were observed between 4 and 8 mg, with no greater effects observed at higher doses. The methadone dose-effect curves were linear across the range of doses tested. High doses of buprenorphine and methadone both attenuated the response to hydromorphone challenge 24 hr later. These data indicate that there is a ceiling on the effects of buprenorphine in humans that may reduce its abuse liability and increase its safety, and indicate that opioid blockade occurs after acute administration of buprenorphine or methadone.

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Background
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Authors: Walsh, S. L., Preston, K. L., Bigelow, G. E., & Stitzer, M. L.
Affiliations: Johns Hopkins University (US)
ORCID: Walsh, S L
Preston, K L
Stitzer, M L
Venue: The Journal of Pharmacology and Experimental Therapeutics
Publisher: Elsevier BV
Published: 1995-07
Volume: 274
Issue: 1
Pages: 361-372
ISSN: 0022-3565 (ISSN-L)
DOI: 10.1016/s0022-3565(25)10510-7
OpenAlex: W2097145370
Cited by: 283
References: 0
Citations by year: 2025: 6 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 12 · 2019: 12 · 2018: 9 · 2017: 12 · 2016: 10 · 2015: 10 · 2014: 8 · 2013: 9 · 2012: 11
FWCI: 9.36
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
PubMed (publishedVersion)
PubMed
Funders: National Institutes of Health (5r18da006165-05, 5r18da006120-05)
National Institute on Drug Abuse (R18 DA 06165, K05DA000050, R18 DA06120)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: buprenorphine, methadone, opioid agonist-antagonist, opioid blockade, opioid use disorder, opioid abuse, sublingual administration, dose-response relationship, ceiling effect, respiratory depression, miosis, euphoria, sedation, abuse liability
MeSH terms: Adult, Buprenorphine, Hydromorphone, Double-Blind Method, Humans, Male, Methadone, Narcotic Antagonists, Receptors, Opioid, Respiration, Cross-Over Studies

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Acute administration of buprenorphine in humans: partial agonist and blockade effects.

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