CoChat
Sign Up
Cited by 89Opioid Use Disorder TreatmentHIV, Drug Use, Sexual RiskForensic Toxicology and Drug Analysis

The epidemic of fentanyl misuse and overdoses: challenges and strategies

Open access
Volkow, Nora D.·2021·World Psychiatry
DOI 10.1002/wps.20846PMC PMC8129846
Open this paper in CoChat — free account

Abstract

Fentanyl, a synthetic opioid with analgesic and anesthetic properties, is currently associated with one of the deadliest addiction crises in the US. Misuse of fentanyl (and fentanyl analogues) has been estimated to be responsible for 48,000 (out of a total of 83,335) overdose deaths in the 12 months ending in June 20201, a rate that has increased more than 29 fold since 2012, when the annual fatalities from fentanyl and its analogues were 1,615. The cases of overdoses and deaths in the US are linked to illegally manufactured fentanyl, which rapidly penetrated the US illicit market since 2013. Though not as pervasively as in the US, increases in overdose deaths due to illicit fentanyl and its analogues have also occurred in Canada, in several European countries (including Estonia, Germany, Finland and the UK) and in Australia2. Fentanyl is relatively easy to synthesize and manufacture, and less difficult to traffic than heroin, since it requires much smaller volumes to transport across borders. It is, therefore, hugely profitable to drug dealers (50-100 times more than heroin), which can be expected to result in an expansion of the illicit fentanyl market across the globe. The majority of opioid-related overdose deaths in the US are the result of fentanyl being ingested as a substitute for heroin or with drugs such as cocaine and methamphetamine that had been adulterated (cut) with the opioid, frequently without users being aware of this. Fentanyl, when used by itself or in combination with other drugs, can be taken orally, injected, snorted or smoked. Most heroin users do not report actively seeking fentanyl, and some are afraid of it but might have no choice because of the higher costs of uncontaminated heroin or its unavailability. When fentanyl is used to adulterate other drugs (heroin, prescription opioids, psychostimulants), it increases their lethality. In the case of psychostimulants, this occurs not only due to the synergistic effects on the cardiopulmonary system, but also because stimulant users, who have no tolerance to opioids, are at very high risk of overdosing when ingesting fentanyl. The unique pharmacological effects of fentanyl have contributed to its widespread misuse and are also the ones that make it a valuable therapeutic for anesthesia and for severe pain management. Fentanyl binds to mu-opioid receptors (MOR), which mediate the analgesic and the rewarding effects of opioid drugs, such as morphine and heroin, as well as their respiratory depressing actions3. However, fentanyl is much more potent at activating MOR-associated signaling than morphine (80-100 fold) or heroin (30-50 fold), and its higher lipophilicity leads to higher and faster brain uptake than for those other drugs. These properties underlie fentanyl's high potency as an analgesic and its rapid actions, which are beneficial for the treatment of breakthrough pain or other severe pain conditions. However, they are also responsible for its powerful rewarding effects, which can rapidly result in physical dependence and in addiction, and for its severe and abrupt inhibition of respiration, which increases the risk for overdose. The treatment of fentanyl addiction (fentanyl opioid use disorder or fOUD) is the same as for other opioid use disorders (OUD). It is based on the use of medications such as methadone (full MOR agonist), buprenorphine (partial MOR agonist) and naltrexone (MOR antagonist)4. These medications are the gold standard for OUD treatment, and multiple studies have shown that they prevent overdoses and relapse in patients exposed to fentanyl. However, clinical cases and anecdotal reports indicate that it is much more challenging to treat patients with fOUD than with other OUD. There are greater difficulties in initiating buprenorphine treatment, resulting from buprenorphine-precipitated withdrawal5 and lower rates of abstinence and retention after six months of buprenorphine treatment6. The slow clearance of fentanyl as a result of its accumulation in fatty tissues may require slower detoxification prior to buprenorphine or naltrexone induction, and the higher rates of tolerance and physical dependence associated with repeated fentanyl use might necessitate higher doses of methadone or buprenorphine than for other OUDs. Treatment of withdrawal symptoms during fentanyl detoxification might be aided, as for other opioids, by the use of the alpha-adrenergic drugs lofexidine and clonidine7. Overall, much more clinical research is needed to investigate how to optimally treat fOUD. Like other opioids, fentanyl can result in overdoses due to its respiratory depressant effects. Signs of overdose include slow irregular breathing, slowing of circulation, sedation, acute respiratory distress, seizures, and coma. With repeated opioid exposure, individuals develop tolerance to the respiratory depressant effects of opioids (tolerance also develops for analgesia and reward), allowing them to tolerate much higher doses than na

Integrity signals

Registry

Crossref · 10.1002/wps.20846

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Volkow, N. D.
Affiliations
National Institutes of Health (US)
Corresponding author
Volkow, Nora D.
ORCID
Volkow, Nora D.
Venue
World Psychiatry
Publisher
Wiley
Published
2021-05-18
Volume
20
Issue
2
Pages
195-196
ISSN
  • 1723-8617 (ISSN-L)
  • 2051-5545
DOI
10.1002/wps.20846
PMC
PMC8129846
OpenAlex
W3163328421
Cited by
89
References
6
Citations by year
2026: 14 · 2025: 24 · 2024: 19 · 2023: 15 · 2022: 13 · 2021: 4
FWCI
11.03
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • World Psychiatry (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
  • Health Sciences › Medicine › Epidemiology › HIV, Drug Use, Sexual Risk
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
Keywords
fentanyl, fentanyl analogs, opioid overdose deaths, illicit drug markets, drug adulteration, heroin substitution, mu-opioid receptor, opioid use disorder, drug policy, harm reduction, prescription opioid misuse, synthetic opioids, drug trafficking, Canada, United States, Europe, US-Canada border

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