Polydrug abuse: a review of opioid and benzodiazepine combination use

Jones, Jermaine D.; Mogali, Shanthi; Comer, Sandra D.

doi:10.1016/j.drugalcdep.2012.07.004

Cited by 703Opioid Use Disorder TreatmentSubstance Abuse Treatment and OutcomesForensic Toxicology and Drug Analysis

Polydrug abuse: a review of opioid and benzodiazepine combination use

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Jones, Jermaine D., Mogali, Shanthi, Comer, Sandra D.·2012·Drug and Alcohol Dependence

DOI 10.1016/j.drugalcdep.2012.07.004PMC PMC3454351

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Abstract

This paper reviews studies examining the pharmacological interactions and epidemiology of the combined use of opioids and benzodiazepines (BZDs). A search of English language publications from 1970 to 2012 was conducted using PubMed and PsycINFO(®). Our search found approximately 200 articles appropriate for inclusion in this paper. While numerous reports indicate that the co-abuse of opioids and BZDs is ubiquitous around the world, the reasons for the co-abuse of these medications are not entirely clear. Though the possibility remains that opioid abusers are using BZDs therapeutically to self-medicate anxiety, mania or insomnia, the data reviewed in this paper suggest that BZD use is primarily recreational. For example, co-users report seeking BZD prescriptions for the purpose of enhancing opioid intoxication or "high," and use doses that exceed the therapeutic range. Since there are few clinical studies investigating the pharmacological interaction and abuse liability of their combined use, this hypothesis has not been extensively evaluated in clinical settings. As such, our analysis encourages further systematic investigation of BZD abuse among opioid abusers. The co-abuse of BZDs and opioids is substantial and has negative consequences for general health, overdose lethality, and treatment outcome. Physicians should address this important and underappreciated problem with more cautious prescribing practices, and increased vigilance for abusive patterns of use.

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Patients who use BZDs and have co-occurring AUD or OUD are at higher risk of morbidity and mortality because of cross-tolerance and combined CNS and respiratory depressant effects.
“patients who use BZDs and have co-occurring alcohol use disorder (AUD) or OUD are at higher risk of morbidity and mortality because of the cross-tolerance and combined CNS and respiratory depressant effects of these substances.23,52”
From Joint Clinical Practice Guideline on Benzodiazepine Tapering: Considerations When Risks Outweigh Benefits (2025) · cites this paper as [52]
Section 6 reports additive CNS and respiratory depression when benzodiazepines are combined with methadone, as well as an association between benzodiazepine–opioid use and fatal and non-fatal overdoses. The paper does not establish cross-tolerance as the cause of that risk or substantiate the same claim for patients with co-occurring alcohol use disorder; its alcohol discussion concerns co-use and treatment outcomes. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Combined use of BZDs and opioids increases the risk of adverse events, including fatal and nonfatal overdose, due to CNS depression caused by both medication classes.
“Combined use of BZDs and opioids increases the risk of adverse events, including fatal and nonfatal overdose, due to the CNS depression caused by both medication classes (see “Patients Co-prescribed Benzodiazepines and Opioids” for further discussion).7,23,52”
From Joint Clinical Practice Guideline on Benzodiazepine Tapering: Considerations When Risks Outweigh Benefits (2025) · cites this paper as [52]
Opioids and benzodiazepines were found to be co-abused by opioid users to enhance opioid intoxication.
“Opioids and benzodiazepines were found to be co-abused by opioid users to enhance opioid intoxication (Jones et al., 2012).”
From National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose deaths: 1999-2009. (2013) · cites this paper as Jones et al., 2012
Previous research has demonstrated that benzodiazepines have greater misuse liability among those with histories of alcohol use disorder and increase the reinforcing effects of opioids when taken in combination.
“Previous research has also demonstrated that benzodiazepines have greater misuse liability among those with histories of alcohol use disorder (23) and increase the reinforcing effects of opioids when they are taken in combination (24)”
From Prevalence and correlates of the misuse of z-drugs and benzodiazepines in the National Survey on Drug Use and Health (2023) · cites this paper as [24]

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Background
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“Previous research has also demonstrated that benzodiazepines have greater misuse liability among those with histories of alcohol use disorder (23) and increase the reinforcing effects of opioids when they are taken in combination (24), consistent with our findings that those with benzodiazepine misuse had higher rates…”
Result
A Qualitative Study of Use of Mindfulness to Reduce Long-Term Use of Habit-Forming Prescription Drugs
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Authors: Jones, J. D., Mogali, S., & Comer, S. D.
Affiliations: Columbia University (US)
Corresponding author: Comer, Sandra D.
ORCID: Jones, Jermaine D.
Comer, Sandra D.
Venue: Drug and Alcohol Dependence
Publisher: Elsevier BV
Published: 2012-09
Volume: 125
Issue: 1-2
Pages: 8-18
ISSN: 0376-8716 (ISSN-L)
DOI: 10.1016/j.drugalcdep.2012.07.004
PMC: PMC3454351
OpenAlex: W1975817655
Cited by: 703
References: 233
Citations by year: 2026: 26 · 2025: 26 · 2024: 52 · 2023: 45 · 2022: 58 · 2021: 63 · 2020: 88 · 2019: 65 · 2018: 67 · 2017: 64 · 2016: 59 · 2015: 39 · 2014: 32 · 2013: 16 · 2012: 1
FWCI: 4.34
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Drug and Alcohol Dependence (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Drug Abuse (DA-09236, DA031022, R01DA022222, R01DA016759, P50DA009236, K01DA030446, DA016759, DA030446-01A, DA022222, R01DA031022, T32DA007294)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
Keywords: polydrug abuse, opioid-benzodiazepine combination, benzodiazepine misuse, opioid abuse, drug interactions, recreational drug use, self-medication, drug overdose, prescribing patterns, abuse liability
MeSH terms: Analgesics, Opioid, Benzodiazepines, Drug Interactions, Humans, Opioid-Related Disorders, Substance-Related Disorders

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Polydrug abuse: a review of opioid and benzodiazepine combination use

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