The DOI matches its Crossref record; 233 of the 233 references it cites were found in a registry or an index.
Polydrug abuse: A review of opioid and benzodiazepine combination use
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Items 201–233 of 233
Valium Use and Abuse by Methadone Maintenance Clients
Hartog, J., & Tusel, D. J. (1987) · International Journal of the Addictions · doi:10.3109/10826088709027476 · Cited by 19
The Neurochemistry of Addiction
Nutt, D. (1997) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/(sici)1099-1077(199706)12:2+ · Cited by 19
FORREST, A. L. (1983) · Anaesthesia · doi:10.1111/j.1365-2044.1983.tb14083.x · Cited by 18
Meiler, A. (2005) · Schweizer Archiv für Neurologie und Psychiatrie · doi:10.4414/sanp.2005.01626 · Cited by 17
Outpatient benzodiazepine detoxification procedure for methadone patients
Mcduff, D. R., Schwartz, R. P., Tommasello, A. C., Tiegel, S. A., Donovan, T., & Johnson, J. L. (1993) · Journal of Substance Abuse Treatment · doi:10.1016/0740-5472(93)90078-g · Cited by 17
High dose buprenorphine for postoperative analgesia
Papworth, D. (1983) · Anaesthesia · doi:10.1111/j.1365-2044.1983.tb13941.x · Cited by 17
Liu, S. J., Evans, D. B., & Wang, R. I. (1978) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)31113-4 · Cited by 17
Dikeos, D., Theleritis, C. G., & Soldatos, C. R. (2008) · Sleep Disorders · doi:10.3109/9780203091715-14 · Cited by 15
Sobrino, A. M. F., Rodríguez, V. F., & Castro, J. L. (2009) · Adicciones · doi:10.20882/adicciones.241 · Cited by 15
Weerts, E. M., Kaminski, B. J., & Griffiths, R. R. (1998) · Psychopharmacology · doi:10.1007/s002130050487 · Cited by 15
Self-injection of flunitrazepam alone and in the context of methadone maintenance in baboons
Ator, N. A., Griffiths, R. R., & Weerts, E. M. (2004) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2004.09.007 · Cited by 14
Detoxification with phenobarbital of alprazolam-dependent polysubstance abusers
Ravi, N. V., MAANY, I., Burke, W. M., DHOPESH, V. P., & WOODY, G. E. (1990) · Journal of Substance Abuse Treatment · doi:10.1016/0740-5472(90)90036-p · Cited by 14
Opiate-related deaths in Dublin
Ward, M., & Barry, J. M. (2001) · Irish Journal of Medical Science (1971 -) · doi:10.1007/bf03167718 · Cited by 14
Buprenorphine, benzodiazepines and prolonged respiratory depression
Mc, S., & Mimpriss, T. J. (1987) · Anaesthesia · doi:10.1111/j.1365-2044.1987.tb04085.x · Cited by 14
Ito, K., Yoshikawa, M., Maeda, M., Jin, X., Takahashi, S., Matsuda, M., Tamaki, R., Kobayashi, H., Suzuki, T., & Hashimoto, A. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.02.068 · Cited by 14
Barnas, C., Rossman, M., Roessler, H., et al. (1992) · Clinical Neuropharmacology · doi:10.1097/00002826-199201001-00060 · Cited by 14
Respiratory effects of intravenous midazolam.
Zacharias, M., Hunter, K. M., & Parkinson, R. (1996) · PubMed · Cited by 13
Moody, D. E. (2011) · Humana Press eBooks · doi:10.1007/978-1-61779-222-9_2 · Cited by 12
Shah, N. S., Patel, V. O., & Donald, A. G. (1979) · Drug Metabolism and Disposition · doi:10.1016/s0022-5347(24)06140-8 · Cited by 12
Quentin, T., Debruyne, D., Lelong‐Boulouard, V., et al. (2005) · Brain Research · doi:10.1016/j.brainres.2005.09.013 · Cited by 11
Prescription and Over-the-Counter Medications
Eaddy, J. L. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-398336-7.00076-0 · Cited by 11
Benzodiazepine Sedation in Critically Ill Patients
Doherty, M. H. (1991) · AACN Advanced Critical Care · doi:10.4037/15597768-1991-4015 · Cited by 10
Handbook of Drug Interactions. A Clinical and Forensic Guide
Flanagan, R. J. (2004) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2004.02081.x · Cited by 8
Autoradiographic Analysis of GABAA Receptors in μ-Opioid Receptor Knockout Mice
Tien, L., Ma, T., Fan, L.-W., Loh, H. H., & Ho, I. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9373-2 · Cited by 7
Drug-Related Deaths in Grampian, Scotland
Stenhouse, G., & Grieve, J. (2003) · Scottish Medical Journal · doi:10.1177/003693300304800405 · Cited by 6
Does oral alprazolam affect ventilation? A randomised, double-blind, placebo-controlled trial
Carraro, G., Russi, E., Büechi, S., & Bloch, K. E. (2008) · Journal of Psychopharmacology · doi:10.1177/0269881108089875 · Cited by 6
[3H]-flunitrazepam binding after morphine treatment and under abstinence syndrome
Soria, C., Fernández‐López, A., Gomez, T., et al. (1991) · Brain Research Bulletin · doi:10.1016/0361-9230(91)90035-i · Cited by 5
Behavioral effects of chronic buspirone administration in the pigeon: Comparison to midazolam
Nader, M. A. (1991) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(91)90022-t · Cited by 5
Cannizzaro, C., Flugy, A. M., Novara, V., et al. (1987) · PubMed · Cited by 5
Schaefer, G. J., & Michael, R. P. (1989) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(89)90347-x · Cited by 3
Prescription and Over-the-Counter Medications
(2012) · PsycEXTRA Dataset · doi:10.1037/e686312012-001 · Cited by 3
Sobrino, F., Fernández, V. L., Castro, J. L., et al. (2009) · Cited by 2
Flagged first, then by citations
Research works printed but not linked: 7
- Backmund, 1999, Intoxikationen Suchtkranker durch Drogen und psychotrope Substanzen, Notarzt, 15, 29
- Fernández-Sobrino, 2009, Benzodiazepine use in a sample of patients on a treatment program with opiate derivatives (PTDO), Adicciones, 21, 143
- Grass, 2001, Drogentod nach Haftentlassung–Untersuchung am Beispiel der Grossstadt Köln, Suchtmed, 3, 97
- Schmidt-Kittler, 2000, Drogenbedingte Todesfälle 1998, Suchtmed, 2, 103
- Strang, 1984, Intravenous benzodiazepine abuse, Br. Med. J., 289, 964
- Teasdale, 1981, Body temperature responses to microinjections of morphine in brain sites containing opiate receptors, Soc. Neurosci. Abstr., 7, 799
- Yanagita, 1970, Self-administration studies on various dependence producing agents in monkeys, Univ. MI Med. Centre J., 86, 216
Cited by
Sorted by citations
Sun, E. C., Dixit, A., Humphreys, K., Darnall, B. D., Baker, L. C., & Mackey, S. (2017) · BMJ · doi:10.1136/bmj.j760 · Cited by 534
The epidemiology of benzodiazepine misuse: A systematic review*
Votaw, V. R., Geyer, R., Rieselbach, M. M., & McHugh, R. K. (2019) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2019.02.033 · Cited by 479
Treatment of Benzodiazepine Dependence
Soyka, M. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1611832 · Cited by 465
Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines
Jones, C. M., & McAninch, J. K. (2015) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2015.03.040 · Cited by 376
Brandt, J., & Leong, C. (2017) · Drugs in R&D · doi:10.1007/s40268-017-0207-7 · Cited by 356
Metadata
- Authors
- Jones, J. D., Mogali, S., & Comer, S. D.
- Affiliations
- Columbia University (US)
- Corresponding author
- 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)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
