Front. Psychiatry Frontiers in Psychiatry Front. Psychiatry 1664-0640 Frontiers Media S.A. 10.3389/fpsyt.2024.1347678 Psychiatry Systematic Review Systematic review on intentional non-medical fentanyl use among people who use drugs Tsang Vivian W. L. 1 * Wong James S.H. 1 2 Westenberg Jean N. 1 Ramadhan Noor H. 1 Fadakar Hasti 1 Nikoo Mohammadali 1 2 Li Victor W. 1 2 Mathew Nick 1 3 Azar Pouya 1 2 Jang Kerry L. 1 Krausz Reinhard M. 1 1 Department of Psychiatry, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada 2 Complex Pain and Addiction Service, Vancouver General Hospital, Vancouver, BC, Canada 3 BC Mental Health & Substance Use Services, Provincial Health Services Authority, Burnaby, BC, Canada

Edited by: Marc Walter, University of Basel, Switzerland

Reviewed by: Brian J. Piper, Geisinger Commonwealth School of Medicine, United States

Thomas Hillemacher, Nuremberg, Germany

Eva-Maria Pichler, Psychiatric Services Aargau, Switzerland

*Correspondence: Vivian W. L. Tsang, vivianwltsang@alumni.ubc.ca

13 02 2024 2024 15 1347678 01 12 2023 18 01 2024 Copyright © 2024 Tsang, Wong, Westenberg, Ramadhan, Fadakar, Nikoo, Li, Mathew, Azar, Jang and Krausz 2024 Tsang, Wong, Westenberg, Ramadhan, Fadakar, Nikoo, Li, Mathew, Azar, Jang and Krausz

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 Objectives

Fentanyl is a highly potent opioid and has, until recently, been considered an unwanted contaminant in the street drug supply among people who use drugs (PWUD). However, it has become a drug of choice for an increasing number of individuals. This systematic review evaluated intentional non-medical fentanyl use among PWUD, specifically by summarizing demographic variance, reasons for use, and resulting patterns of use.

 Methods

The search strategy was developed with a combination of free text keywords and MeSH and non-MeSH keywords, and adapted with database-specific filters to Ovid MEDLINE, Embase, Web of Science, and PsychINFO. Studies included were human studies with intentional use of non-medical fentanyl or analogues in individuals older than 13. Only peer-reviewed original articles available in English were included.

 Results

The search resulted in 4437 studies after de-duplication, of which 132 were selected for full-text review. Out of 41 papers included, it was found that individuals who use fentanyl intentionally were more likely to be young, male, and White. They were also more likely to have experienced overdoses, and report injection drug use. There is evidence that fentanyl seeking behaviours are motivated by greater potency, delay of withdrawal, lower cost, and greater availability.

 Conclusions

Among PWUD, individuals who intentionally use fentanyl have severe substance use patterns, precarious living situations, and extensive overdose history. In response to the increasing number of individuals who use fentanyl, alternative treatment approaches need to be developed for more effective management of withdrawal and opioid use disorder.

 Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42021272111.

 addiction fentanyl overdose crisis substance use opioid use disorder section-in-acceptance Addictive Disorders Introduction

Fentanyl and its analogues such as alfentanil, sufentanil and remifentanil were first introduced into clinical practice (carfentanil in veterinary medicine) as μ-opioid receptor agonists and potent relatively short-acting analgesic agents. Fentanyl is between 50-fold and 100-fold more potent than morphine, thereby offering greater ability to manage intractable pain, breakthrough cancer pain and to produce balanced intravenous (IV) anaesthesia (1). The unique pharmacological properties of fentanyl and its widespread prevalence in the current North American drug market have contributed to alarming rates of fentanyl-related overdose deaths (2).

The use of non-medical fentanyl and its analogues has changed drastically over the last ten years. (3) In the 2000s and the early years of non-medical fentanyl use, fentanyl was diverted from clinical settings, mostly in the form of transdermal patches. Fentanyl patches were “cooked into fentanyl tea” and the fluid was injected intravenously along with extracted fentanyl. (4) This was a rare occurrence, and the practice was only found in parts of Europe (e.g., in Germany). A decade later, fentanyl made its way into the street drug market. Due to its synthetic quality, high availability, and lower cost, fentanyl was commonly mixed into other desired substances to offset the cost for producers and sellers. (3) Originally a contaminant, fentanyl has now become increasingly present in street opioids, stimulants and hallucinogens. (5) Over time, people who use drugs (PWUD) have also become increasingly accustomed to fentanyl added to other illicit substances. Based on legally available precursors, fentanyl has also increasingly been produced in local private laboratories. (3) Combined with a lower cost of production, increased availability in the illicit drug market, and the rapid, intense onset of effect, these attributes have altered fentanyl’s identity from an unwanted contaminant to a desirable drug of choice. (2) However, the demographic characteristics and comorbidities common to individuals who prefer fentanyl to other substances and use it intentionally as their drug of choice are unknown in the current literature. Intentional fentanyl use has been defined in this review as seeking fentanyl in the illicit drug market or using substances that are known to contain fentanyl; in other words, having fentanyl as one’s drug of choice, seeking out fentanyl, and not using fentanyl by accident. The details around patterns of use and motivation to use are also currently unknown.

This systematic review aimed to evaluate the evidence on intentional fentanyl use among PWUD by summarizing demographic variance, reasons for use, and resulting patterns of use to inform the development of effective interventional approaches and settings and identify critical research questions.

 Methods Review protocol

The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to ensure the details in the methodology is comprehensive (6). A protocol for this review has been registered with PROSPERO (registration number: CRD42021272111) (7). Research ethics board review was not required as this study relies exclusively on publicly available information that is legally accessible to the public.

 Search strategy

The search strategy in this study was developed with a combination of free text keywords and MeSH and non-MeSH keywords. Search items were adapted with database-specific filters. Four different databases: Ovid MEDLINE (1860-May 2021); Embase (1952-May 2021); Web of Science (1900-May 2021); and PsychINFO (1900-May 2021). The search strategies for Ovid MEDLINE, Embase, Web of Science, and PsychINFO are provided in the supplemental material ( Supplementary Tables S1A-D ). References of all included papers were hand-mined, and any additional documents were added from gray literature such as from thesis dissertations and Google Scholar. The last search was completed on May 29, 2021.

 Study inclusion and exclusion criteria

Studies were included if they reported data on the intentional use of non-medical fentanyl or any fentanyl analogues in PWUD older than 13. The term PWUD refers to those who use illicit drugs or use prescription drugs non-medically. Papers from all regions of the world were considered as long as they were written or were available in the English language. Only peer-reviewed original articles were included, including case reports/series. Letters, reviews, meta-analyses, toxicology or coroner’s reports, commentaries, and editorials were excluded. Studies that included non-human participants, did not mention explicit intentional fentanyl use, or only discussed medical indications for fentanyl were excluded. Control or other comparison groups were not relevant to this study and the outcome of interest was intentional fentanyl use.

 Screening and data extraction

The PRISMA flow diagram was used to review selected articles in sequential fashion ( Figure 1 ). Titles and abstracts of studies retrieved using the search strategy were screened by at least two of five reviewers (VWLT, JSHW, JNW, HF, NR). Any inconsistencies were reviewed by a third reviewer (VWLT or JSHW). The inclusion and exclusion criteria were strictly adhered and all articles were independently screened to minimize bias. Full text documents were independently assessed by at least two of five reviewers (VWLT, JSHW, JNW, HF, NR) for inclusion and any disagreements were resolved by consensus. A standardized table with predetermined categories was used for independent data extraction by at least two reviewers. Data on patient demographics, study setting, study methods, motivations for drug use, patterns of use, and associated attributes or behaviours of participants were collected.

Flow of literature search. (MEDLINE, Medical Literature Analysis and Retrieval System Online; EMBASE, Excerpta Medica database) Legend. Wrong comparator: original study had not included a group or population with intentional fentanyl use for comparison or analysis within the study text.

 Study quality assessment

Quality synthesis and evaluation of bias for article inclusion was completed in alignment with

the Newcastle-Ottawa Quality Assessment scale for cohort and case-controlled studies (8). Cross-sectional studies were evaluated with the modified Newcastle-Ottawa Quality Assessment scale for comparable results (9). Qualitative studies were appraised with the Critical Appraisal Skills Program (CASP) checklist (10). For case studies and series, we noted the following criteria for assessing methodological quality: timeline of recruitment, prospective or retrospective recruitment. Meta-analyses and reviews were not included in this study and there were no randomized controlled trials found.

 Analysis

Any inconsistencies were brought up to VWLT for review and final decision. The approach for analysis was conducted by separation of studies into three categories: studies discussing intentional fentanyl use with other substance use but where data were not distinguishable, studies with intentional fentanyl use only, and studies comparing intentional fentanyl using cohorts with non-intentional fentanyl using cohorts. This was conducted by three reviewers (NR, JSHW, JNW) with a second reviewer for each grouped analysis. Details of interest captured for each category of studies include demographic descriptors such as mean age, gender distribution, racial background, and socioeconomic status. Other relevant details captured include years of substance use, substance use patterns, overdose history, motivation for substance use, and usage patterns. In order to calculate pooled means for age, we estimated means from studies which only reported medians by using Luo et al., 2018’s model (11, 12).

 Results

The search resulted in 4437 studies after de-duplication, 132 were selected for full-text review, and 41 were included ( Figure 1 ). Of the 41 studies included, 23 were in the United States (13–35); seven in Canada; (36–42) two in Sweden; (43, 44) one each in Australia, (45) Germany, (46) Denmark, (47) France, (48) Estonia, (49) the UK, (50) and Turkey. (51) Two studies were done online with no note of specific country involvement ( Table 1 ) (52, 53). A mean of 62·63% of participants were male and 64·05% were White. The mean of average age was 41·36 (SD=10·86).

Study details for all included articles (N=41).

Sample size (N) How did study determine intentional fentanyl use Separation possible? Recruitment method City, country Timelines Methodology of study Method of data analysis
Comprehensive Description of Studies Involving Intentional Fentanyl Use That is Undistinguishable from Other Substance Use (N=19)
Amlani et al. (36) 242 Self-reported intentional use No HR services across BC British Columbia, Canada Feb - Mar 2015 Cross-sectional linking demographics & substance usage patterns with urine tests Descriptive statistics
Bach et al. (15) 165 (survey), 129 (urine samples) Survey No Triage screening of patients for substance use Baltimore, Maryland, USA May - July 2018 Cross-sectional study, urine analysis & survey Urine analysis
Balsamo et al. (52) 86,445 Information provided on Reddit comments No Publicly available Reddit data set Online - Reddit 2014- 2018 Semi Automatic information retrieval algorithm Reddit Statistical modeling
Bardwell et al. (37) 21 Interviews No Recruited from two cohort studies Vancouver, Canada Dec 2019- Mar 2020 Qualitative semi-structured interviews Thematic coding
Buresh et al. (16) 994 Self-reported intentional use Yes SSP & HIV treatment services, community outreach Baltimore, Maryland Nov 2017- June 2018 Cross-sectional study quantitative survey Standard descriptive statistic
Ciccarone et al. (13) 38 Qualitative interview No Recruited during daily activities Massachusetts & Hampshire June 2016 Qualitative rapid study & semi-structured interview Analytic memos, inductive analysis
Daniulaityte et al. (18) 60 Self-reported heroin/NPF use No Online & community outreach Dayton, Ohio, US May 2017-Jan 2018 Semi structured interviews & urine drug screen Descriptive statistics
Gryczynski, et al. (19) 1,174 (review records), 114 (anonymous surveys) Survey No Convenience sampling of outpatients Baltimore, Maryland, US 2018 Review of treatment records & anonymous survey Descriptive statistics & logistic regression model
Kenney et al. (21) 231 Interview No Patients seeking opioid withdrawal management Fall River, Massachusetts Apr - Sept 2017 Survey Quantitative, descriptive, inferential statistics
Krause et al. (46) 960 (UDS), 401 (questionnaire) Questionnaire No Recruited from outpatient clinics Munich, Germany 2008 - 2012 Cross sectional- Urine analysis & questionnaire Quantitative
McLean et al. (27) 125 (surveys), 30 (interviews) Interviews No Targeted sampling, advertised in local drug treatment clinics & community Allegheny, Fayette, Greene, Washington July 2017 - July 2018 Qualitative interview & surveys NVivo, descriptive statistics
Moeller et al. (44) 24 threads with 8761 posts Some of the users purchased fentanyl analogs wittingly N/A Online through flashback.org Sweden Sept 2012-July 2019 Thematic analysis of a public internet forum Flashback Thematic analysis
Nolte et al. (30) 589 (survey), 22 (in-depth interview) Interviews No Street outreach, HR agencies & referrals Rural Northern New England, Northeastern United States, May 2018 – Oct 2019 Interview & survey Descriptive statistics & thematic analysis
O'Rourke et al. (31) 373 Cross-sectional survey No Recruited PWID from a SSP & in community locations Cabell County, West Virginia USA June - July 2018 Cross sectional survey with statistical analysis Descriptive statistics
Park et al. (32) 326 Survey No Targeted sampling at SSP & HR services. Baltimore, Maryland; Boston, Massachusetts; & Providence, Rhode Island June – Oct 2017 Survey, interview Descriptive statistics & logistic regression analysis
Silverstein et al. (33) 63 N/A No Community outreach Dayton, US May 2017- June 2019 Qualitative interviews NVivo, thematic coding
Uuskula et al. (49) 110 Interviewer-administered questionnaire No Respondent-driven sampling Tallinn, Estonia 2009 to 2013 Cross-sectional & observational Quantitative analysis
Wallace et al. (41) 187 Self-reported intentional use No Convenience sampling from sites distributing clean injecting supplies Victoria, Canada June - Sept 2016 Cross-sectional survey Logistic regression analysis
Weicker et al. (35) 20 Interviews No Street outreach in targeted locations Baltimore US Oct 2018 - Dec 2019 Qualitative interviews MAXDQA via priori & inductive codes
Comprehensive Description of Studies Involving Intentional Fentanyl Use Only (N=13)
Eiden et al. (48) 1 Self-reported intentional use N/A Patient admitted to emergency department France May 2016 Case report Descriptive statistics
Firestone et al. (38) 25 Qualitative interviews No With the help of community service provider & peer contacts Toronto, Ontario, Canada Mar- June 2007 Exploratory (interview-based) qualitative study N/A
Gecici et al. (51) 1 Self-reported intentional use Yes Inpatient hospital admission Turkey 2010 Case report Case report
Guerrieri et al. (43) 40 Witnesses, police findings No Report of a series of forty fatal intoxications Sweden Apr-Oct 2016 Femoral blood analysis & case studies Analyst1 1.6.2 software
Gunn et al. (20) 21 Interviews N/A Flyers & referrals at local SSP, community outreach services & primary care practices Boston, MA, United States. May-Nov 2018 Qualitative interviews NVivo, deductive & inductive thematic analysis
Kilwein et al. (22) 122 Questionnaire (descriptive survey) No Online postings 34 US states Feb 2016 - Apr 2017 Descriptive study, fentanyl questionnaire N/A
Kimergard et al. (47) 14 Medical history during intake as a patient N/A Outpatients seeking treatment for fentanyl smoking from an addiction service Southern Denmark Aug- Dec 2015 Retrospective case review N/A
Lyttle et al. (50) N= 1 Applied 5 patches to end her life Yes N/A Bristol, UK N/A Case report Case report
Marquardt et al. (25) 1 Observed by paramedics No Man seen by paramedics Sacramento, California, United States 1994 Case report Descriptive statistics
Mrvos et al. (29) 76 Ingested intact fentanyl patches Yes Three RPIC medical record databases Pittsburgh, USA 2000 & 2008 Retrospective case review Descriptive statistics
Reeves et al. (53) 1 Injected content of transdermal patch No Inpatient hospital admission N/A 2002 Case report N/A
Tharp et al. (34) 4 Transdermal patch use & injected No Post-mortem analysis North Carolina, USA Jan 1997 - July 2001 Post-mortem analysis N/A
Woodall et al. (42) 7 Witness reports & autopsy No Identified via a retrospective analysis of fentanyl-related deaths Ontario, Canada Jan 2002 - Dec 2004 Post-mortem autopsy, blood analysis & toxicological findings Toxicological analysis
Comprehensive Description of the Intentional Fentanyl Using Subpopulations Among Studies Comparing Intentional Fentanyl with Non-intentional Fentanyl (N=9)
Antoine et al. (14) 4 Self-reported intentional use Yes Participants were part of RCT of a sleep medication during opioid tapering Not clear what city, but all authors from Maryland; United States 2021 Case series Descriptive statistics
Chandra et al. (17) 104 Self-reported intentional use Yes Recruited from an addiction treatment setting using clinic-based advertisements & community New Haven, Connecticut, US July 2018 - Oct 2019 Cross-sectional- survey using an audio computer-assisted self-interview Multivariable logistic regressions, descriptive statistics
Geddes et al. (45) 2378 Survey N/A The annual Australian NSP survey Australia 2014 Cross sectional - self-administered questionnaire & antibody testing. Descriptive statistics & logistic regression models
Karamouzian et al. (39) 303 Self-reported intentional use Yes Recruited from HR sites British Columbia, Canada May - Aug 2018 Cross-sectional study, & urine sample & survey Multinomial logistic regression models
Kline et al. (23) 432 Survey No Methadone maintenance, acute residential detoxification programs New Jersey, USA Oct 2018 - Mar 2019 cross-sectional quantitative study Descriptive statistics
Macmadu et al. (24) 199 Self-reported intentional use Yes Targeted canvassing, snowball sampling & online Rhode Island, United States Jan 2015 - Feb 2016 Cross-sectional study with interviews & surveys. Descriptive statistics & logistic regression models
Mazhnaya et al. (26) 311 Survey Yes Purposive sampling at the HR program & community Cabell County, WV June- July 2018. Audio computer-assisted self-interview (ACASI) Descriptive statistics, Kolmogorov- Smirnov, regression
Mitra et al. (40) 578 Self-reported intentional use Yes Self-referral & community outreach Vancouver, Canada Dec 2016 Nov 2017 Questionnaire Descriptive statistics, logistic regression model
Morales et al. (28) 308 Self-report via survey Yes Convenience sampling at HR organizations Baltimore, Boston, Massachusetts, & Rhode Island June – Oct 2017 Cross sectional surveys Descriptive statistics

NPF, non-pharmaceutical fentanyl; PWU, people who use; SSP, syringe service programs; HR, harm reduction; UDS, urine drug screening; HIV, human immunodeficiency virus; N/A, not applicable.

Outcomes were analyzed in three groups. Nineteen studies discussed intentional fentanyl use with other substance use where data were not distinguishable ( Table 2 ), 13 studies discussed intentional fentanyl use only ( Table 3 ), and 9 studies compared intentional fentanyl using cohorts with non-intentional fentanyl using cohorts ( Table 4 ). It should be noted that there was little data to extract from studies examining intentional fentanyl use only, as 11 of the 13 studies were case reports/series. Moreover, of the 11 case reports/series, 3 were post-mortem analyses, all of which reported illicit intentional use of fentanyl. (34, 42, 43) More comprehensive details are available as online supplements ( Supplementary Tables S2 – S4 ).

Comprehensive description of studies involving intentional fentanyl use that is undistinguishable from other substance use (N=19).

Sample Size Age (Years) Gender (% Male) Overdose history Race/Ethnicity Socioeconomic factors
Amlani et al. (36) 242 Range19 – 29: 19% 30 – 39: 28%40 – 49: 34%50+: 19% 58% Overdose within last month: 10%Overdose within last week: 2% N/R N/R
Bach et al. (15) 165 Estimated Mean (SD): 47.95 (14.13)Median (IQR): 49 (38 – 57) 77.00% Opioid overdose: 42 (25.5%) N/R N/R
Balsamo et al. (15) 86,445 N/R N/A N/A N/A N/A
Bardwell et al. (37) 21 Estimated Mean (SD): 48.3 (7.4)Range: 35 – 63Median: 48 57.14% N/R White: 12Indigenous: 9 Employment - Income generation (last 30 days) Social assistance: 21Drug selling: 16Recycling/vending: 13Part-time employment: 10Theft: 8Panhandling/busking: 5Sex work: 1
Buresh et al. (16) 994 Mean (SD): 55 (9.1) 65% Reported a recent non-fatal overdose (any drug): 35 (4%) African American: 84% Education - 46% completed high schoolEmployment – employed: 14%Employment – income <$5K: 70%Medical history - 31% HIV positiveHousing - 10% reported homelessness in the prior 6 monthsRelationship - 48% ever married
Ciccarone et al. (13) 38 Range: 19 - 52 60.52% N/R Of those stating their ethnicity:White: 16African American: 3Hispanic: 10Mixed ethnicity: 7 N/R
Daniulaityte et al. (18) 60 Mean (SD): 39 (9.5) 48.3% Mean unintentional drug-related overdoses in their lifetime: 2.8Self-perceived risk of overdose as high: 11.7%Self-perceived risk of overdose as moderate: 33% White: 91.7%African American: 6.7%Other: 1.7% Education - High school education or less: 70%Education - High school or GED: 36.7%Education - some college or more: 31.7%Employment - Unemployed: 75%
Gryczynski et al. (19) 1,174 Mean (SD): 40.7 (11.4) 65.50% N/R Black/African-American: 59.6%White: 40.4% Relationship - 5.5% marriedRelationship - 94.5% not marriedMedical history - 58.7% current mental health diagnosis
Kenney et al. (21) 231 Mean (SD): 34.0 (9.2) 73.20% Ever overdosed: 127 (55.0%) White: 193 (83.6%) Black: 6 (2.6%)Other: 32 (13.0%)Latino: 27 (11.7%) Education - mean years education: 12.0 (±1.7)
Krause et al. (46) 960 (UDS)401 (questionnaire) Range:18 - 30: 19.4%30 - 40: 41.1%>40: 39.5% 64.60% N/R N/R N/R
McLean et al. (27) 125 Mean (SD): 34.5 (8.7)Range: 20 – 62 66.4% Overdosed and needed medical intervention to be revived:Yes, once: 13Yes, more than once: 19 Non-Hispanic White: 80% Non-Hispanic Black: 6.7% Education - 10% didn’t complete high school Education - 43.3% completed high school Employment - 56.7% unemployed
Moeller & Svensson (44) 24 threads with 8761 posts on Flashback.org N/A N/R N/R N/R N/R
Nolte et al. (30) 589 N/R 58.7% N/R White: 90.3%Non-Hispanic: 95.2% N/R
O'Rourke et al. (31) 373 Mean (SD): 35.8 (8.6) 59.50% In the past 6 months:Experienced a drug overdose 43.7% White, non-Hispanic: 83.4% Education - had at least a high school education: 71.7% Relationship - either married or in a relationship: 47.3% Housing - consider themselves homeless: 57.1% Arrest - reported been recently arrested: 30.6%
Park et al. (32) 326 Range:< 35: 23.9%≥ 35: 76.1% 59.1% Had a history of overdose: 64%Overdosed more than once: 34.7% Non-White: 64% Education - 39% < high schoolHousing - 68.7% currently homelessEmployment - 86.8% unemployedEmployment - 57% had sold drugs in thepast 3 monthsIncarceration - history of arrest 47%Arrest - 46.5%
Silverstein et al. (33) 63 Mean (SD): 38.9 (10.6)Range: 19 - 70 54% N/R Non-Hispanic White: 85.7%African American: 12.7%Hispanic: 1.6% Education - Less than secondary: 22.2%Education - Secondary school degree: 27%Education - Some college or tech school: 38.1%Education - Post secondary: 12.7%Housing - Shelter: 4.8%Housing – Streets: 1.6%,Employment - Employed full time: 12.7%Employment - Part time: 20.6%Employment - Unemployed: 47.6%Employment - Unemployed due to disability: 15.9%
Uuskula et al. (49) 110 Mean (SD): 24.5 (7.5) 69.10% N/R N/R Education - 52% had education (10+ years)Employment - 37% were employedIncarceration - 25% have been in prisonMedical history - 19% HIV
Wallace et al. (41) 187 Estimated Mean (SD): 40.4 (12.7)Median (IQR): 40 (32 – 49) 64.7% Overdosed at least once in the previous 6 months: 56 (29.9%) White: 62% N/A
Weicker et al. (35) 20 Estimated Mean (SD): 37.4 (9.9)Range: 20-57Median: 37 45% N/R Black:10White: 9Multiracial: 1 Housing – homeless: 75%

UDS, urine drug screening; HIV, human immunodeficiency virus; SD, standard deviation; N/R, not reported; N/A, not applicable.

Comprehensive description of studies involving intentional fentanyl use only (N=13).

Age (years) Gender (% male) Race/Ethnicity (% White) Substance use patterns Overdose history Socioeconomic factors
Eiden et al. (48) 59 100% N/R Transmucosal fentanyl use, 5 to 15 cigarettes/day: 100% N/R N/R
Firestone et al. (38) Range: 18 - 50 60% N/R Participants used a “variety of other drugs” but they were not specified. N/R N/R
Gecici et al. (51) 59 100% 100% History of cannabis abuse for 20 years, but stopped 10 years ago: 100%Use of transdermal fentanyl patches 3-4 times per day: 100% N/R Had 3 children.Was a driver but has not worked in the last 1.5 years.
Guerrieri et al. (43) Mean (SD): 32.05 (9.49)Range: 18 - 53 85% N/R Acrylfentanyl was identified along with other drugs: 97.5%No other drugs but acrylfentanyl were found: 2.5%5 cases were discussed more extensively: fentanyl nasal spray (3/5), fentanyl tablets (2/5) Fatal accidental OD: 85%Possibly suicide: 15% N/R
Gunn et al. (20) 18 – 25 (n = 10)35+ (n = 11) 52% 100% English Speaking 9.5%: actively seeking fentanyl42.9%: passive use of fentanyl (doesn't seek it)47.6%: does not want to use fentanyl History of at least 1 OD: 95.2% N/R
Kilwein et al. (22) Mean (SD): 32.32 (10.28)Range: 18 - 67 46% 71.3% Lifetime history of other illicit drug use: 94%Lifetime history of nonmedical use of another opioid: 73.8% N/R Some high school education: 4.9%A high school diploma/GeneralEducation Diploma (GED): 35.2%A trade/technical degree: 12.3%Some college education: 28.7%A bachelor’s degree: 14.8%A graduate/professional degree: 4.1%Enrolled in college: 18.9%
Kimergard et al. (47) Mean (SD): 27.9 (4.7)Range: 23 - 37 93% N/R Cannabis: 88.9%Other opioids/metabolites, including codeine, morphine, oxycodone & oxymorphone: 66.7%Cocaine: 44.4%Amphetamine: 33.3% N/R N/R
Lyttle et al. (50) 15 0% N/R N/R OD & attempted suicide by use of fentanyl patches: 100% N/R
Marquardt et al. (25) 34 100% N/R Inhalation of fentanyl patch: 100% N/R N/R
Mrvos et al. (29) Mean: 32.6 Range: 15 - 56 59.20% N/R Ingestion of whole fentanyl patches: 100% N/R N/R
Reeves et al. (53) 35 0% N/R History of IV drug use: 100% Death by OD: 100% N/R
Tharp et al. (34) Mean (SD): 38.5 (2.89) Range: 35 - 42 100% 100% History of drug use: 75%No known history of drug use: 25% Fatal fentanyl OD, suicide: 25%Fatal fentanyl poisoning, accidental: 50%Fatal fentanyl toxicity, accidental: 25% N/R
Woodall et al. (42) Mean (SD): 39.14 (10.21)Range: 20 - 51 57% N/R Most had a history of drug abuse Fatal fentanyl OD: 28.6%Fatal fentanyl & ethanol OD: 42.9%Mixed drug intoxication death: 14.3%Death due to fentanyl & medical causes: 14.3% N/R

IV, intravenous; N/A, not applicable; N/R, not reported; OD, overdose; SD, standard deviation.

Comprehensive description of the intentional fentanyl using subpopulations among studies comparing intentional fentanyl and non-intentional fentanyl use (N=9).

Intentional fentanyl use group Non-intentional fentanyl use group
Group Age (years) Gender (% male); Ethnicity (% Caucasian) Substance use patterns Overdose Socioeconomic Comparison group Age (years) Gender (% male); Ethnicity (% Caucasian) Substance use patterns Overdose Socioeconomic
Antoine et al. (14) Intentional fentanyl use (n=3) 18-25: 33% (1/3)26-40: 33% (1/3)41-55: 33% (1/3) 100%; 100% Heroin/fentanyl use intranasal: 100% (3/3)Prescription opioid misuse: 33% (1/3)Cocaine use: 66% (2/3) N/R N/R Non-intentional fentanyl use** (n=1) 26‐40: 100% (1/1) 0%; 0% Heroin/fentanyl use intravenous/intranasal: 100% (1/1) N/R N/R
Chandra et al. (17) Purposeful fentanyl use (n=45) Mean (SD): 37.5 (8.8) 64.4%; 82.2% Heroin: 86.7%Cocaine: 88.9%Poly drug: 91.1%Inject daily: 28.9% Non-fatal OD in past year: 28.9% High school graduate: 75.6%Income level < $10,000: 68.9%Currently married/living with partner: 28.9%Homeless in past year: 60.0% No purposeful fentanyl use (n=59) Mean (SD): 43.1 (9.3) 49.2%; 74.6% Heroin: 15.3%Cocaine: 78.9%Poly drug 85.6%Inject daily: 18.3% Non-fatal OD in past year: 11.9% High school graduate: 67.8%Income level <$10,000: 78.0%Currently married/living with partner: 23.7%Homeless in past year: 47.5%
Geddes et al. (45) Recent fentanyl injection (n=193) <30 years: 12%30–39 years: 43%40–49 years: 33%>49 years: 12% 75%; 77% Fentanyl as the main opioid in last 6 months: 78%Heroin as the drug last injected: 32%Currently in OST: 37%Daily injection: 78% Overdose in last 12 months: 37% HCV negative: 38%HCV positive: 62% No recent fentanyl injection (n=655) <30 years: 12%30–39 years: 37%40–49 years: 32%>49 years: 19% 69%; 84% Currently in OST: 34%Not currently in OST: 62%Daily injection: 61% Overdose in last 12 months: 21% HCV negative: 38%HCV positive: 62%
Karamouzian et al. (39) Known use (n=117) ≥50: 22.2%40–49: 32.1%30–39: 52.2%19–29: 48.33% 38.7%; N/R Cannabis: 39.2%Methadone: 64.1%Heroin/morphine: 61.8%Oxycodone: 85.7%Crystal meth: 55.3%Cocaine: 57.6%Crack: 52.3%Benzodiazepine: 51.4%Polydrug: 66.4%Preferred ROAinjection: 55.5% Experienced non-fatal overdose in the last 6 months: 51.8% Unstable housing (current): 52.3%Paid employment: 27.2%Medium/large urban cities: 48.1%Small urban/rural communities: 22.3% No fentanyl use (n=120) ≥50: 66.6%40–49: 33.3%30–39: 26.1%19–29: 36.6% 42.3%; N/R Cannabis: 47.7% Methadone: 20.5%Heroin/morphine: 9.0% Oxycodone use: 14.2%Crystal meth: 24.4%Cocaine: 28.8%Crack: 35.3%Benzodiazepine: 34.2%Polydrug: 13.1%Preferred ROAinjection: 16.8% Experienced non-fatal overdose in the last 6 months: 22.2% Unstable housing (current): 31.4%Paid employment: 56.3%Medium/large urban cities: 25.6%Small urban/rural communities: 63.39%
Kline et al. (23) Persistent overdose subgroup* (n=40) Mean (SD): 38.03 (11.49) 72.5%; 69.2% Often/always mixes opioids with one or more other drugs: 70%Heavy alcohol use: 40%IV Injection: 72.5% Mean number of overdoses: 8.03 Homeless: 15% No lifetime overdoses (n=238) Mean (SD): 41.02 (11.72) 48.3%; 46.4% Often/always mixes opioids with one or more other drugs: 51.3%Heavy alcohol use: 17.2%IV Injection: 28.2% Mean number of lifetime overdoses: N/A Homelessness: 10.1%
Macmadu et al. (24) Self-report intentional use of FCH in prior 6 months (n=22) Median (IQR): 27 (25–28) 72.7%; 95.5% Heroin: 81.8%NMPO: 63.6%Cocaine: 36.4%Non-medical benzodiazepine: 59.1%Diverted pharmaceutical fentanyl: 72.7%Injection drug use: 40.9% Ever experienced a non-fatal overdose: 63.6% Education beyond high school: 45.5%Ever detained in jail: 59.1%Ever homeless: 77.3%Mental health diagnosis: 86.4%Ever HCV positive: 33.3% No FCH use in prior 6 months (n=177) Mean (IQR): 24 (22–27) 64.4%; 57.1% Heroin: 18.6%NMPO: 45.2%Cocaine: 7.9%Non-medical benzodiazepine: 26.6%Diverted pharmaceutical fentanyl: 6.8%Injection drug use: 9.0% Ever experienced a non-fatal overdose: 22.0% Education beyond high school: 50.9%Ever detained in jail: 45.8%Ever homeless: 51.4%Mental health diagnosis: 71.2%Ever HCV positive: 8.3%
Mazhnaya et al. (26) Prefer drugs containing fentanyl (n=135) Median (IQR): 35 (28–40) 48.9%; 84.4% Injection drug use past 6 monthsFentanyl: 83.7%Heroin: 97.8%Buprenorphine or Buprenorphine/Naloxone: 25.2%Painkillers: 25.2%Crystal meth: 76.3%Speedball: 55.6%Cocaine: 49.6%Other drugs use past 6 months:Smoked heroin: 23.7%Swallowed fentanyl: 17.8%Swallowed painkillers: 34.8%Swallowed Buprenorphine or Buprenorphine/Naloxone: 30.4% Number of overdoses experienced in past 6 months0 :41.5%1-2: 29.6%3-5: 15.6%5+: 13.3% High school graduate: 71.6%Single: 55.2%Sexual Minority: 17.2%Homeless: 60%Unemployed: 71.9%Food insecurity: 68.9%Transactional sex work in past 6 months: 68.9%Arrested in past 6 months: 37.8% Do not prefer drugs containing fentanyl (n=176) Median (IQR): 37 (31–42) 67.1%; 93.8% Injection drug use, past 6 months:Fentanyl: 57.4%Heroin: 86.9%Buprenorphine or Buprenorphine/Naloxone: 29.6%Painkillers: 22.2%Crystal meth: 74.3%Speedball: 35.2%Cocaine: 30.7%Other drug use past 6 months:Smoked heroin: 13.1% Swallowed fentanyl: 5.7%Swallowed painkillers: 28.4%Swallowed Buprenorphine or Buprenorphine/Naloxone: 31.3% Number of overdoses experienced in past 6 months0: 53.4%1-2: 25.6%3-5: 12.5%5+: 8.5% High school graduate: 72.2% Single: 49.4%Sexual Minority: 13.1%Self-homeless: 56.3%Unemployed: 62.5%Food insecurity: 65.3%Transactional sex work in past 6 months: 11.4%Arrested in past 6 months: 35.8%
Mitra et al. (40) Self-reported intentional fentanyl users (n=386) Median (IQR): 39 (28.2-50.4) 66.1%; 52.5% Heroin: 60.9%Prescription opioid: 3.6%Stimulant: 43.5%OAT: 58.8%Injection drug use: 87% High/moderate perceived risk of fentanyl overdose (men; women): 50.4%; 40.5% DTES residency: 63.0%Incarceration: 9.9%Exchanged money for sex: 11.4%Experienced violence: 13.6% Self-reported unintentional fentanyl exposure (n=192) Median (IQR): 44.7 (34.6-53.4) 54.2%; 50.0% Heroin: 43.2%Prescription opioid: 5.7%Stimulant use: 41.7%OAT: 55.7%Injection drug use: 80.7% High/moderate perceived risk of fentanyl overdose (men; women): 52.0%; 62.5% DTES residency: 73.0%Incarceration: 8.3%Exchanged money for sex: 12%Experienced violence: 14.6%
Morales et al. (28) Preference for fentanyl (n=83) Median (IQR): 38 (32–46) 62.7%; 59% Prescribed opioid: 53%Medication-assisted treatment: 75%Daily drug use: 91.6%Heroin injection: 78.3%Heroin, smoked/snorted: 32.5%Crack cocaine use: 73.5%Snorted cocaine: 19.3%Cocaine injection: 44.6%Speedball injection: 53%Injection drug use: 83.1% Never: 25.3%More than a year ago: 31.3%Within the last year: 43.4%Suspected due to fentanyl: 86.1% Currently homeless: 69.9%Main sources of income last 3 months illegal work: 63.9%Arrested / incarcerated, last year: 59.0% Does not prefer fentanyl (n=225) Median (IQR): 45 (37–52) 59.1%; 29.3% Prescribed opioid use: 53.3%Medication-assisted treatment: 70%Daily drug use: 75.6%Heroin injection: 64%Heroin, smoked/snorted: 51.1%Crack cocaine use: 69.3%Snorted cocaine: 28%Cocaine injection: 35.1%Speedball injection: 42%Injection drug use: 68.4% Never: 37.3%More than a year ago: 17.3%Within the last year: 45.3%Suspected due to fentanyl: 91 (89.2%) Currently homeless: 68.0%Main sources of income, last 3 months illegal work: 41.3%Arrested / incarcerated, last year: 42.2%

*Significant finding that this subgroup would more likely take fentanyl intentionally.

**Self-reported heroin use; UDS came back positive for fentanyl.

N/R, not reported, N/A, not applicable; FCH, fentanyl-contaminated heroin; DTES, downtown east side; OAT, opioid agonist treatment.

 Demographics

Regarding age among studies comparing intentional fentanyl using cohorts with non-intentional fentanyl using cohorts, participants were a pooled mean of 37·65 years (SD=13·77) in the intentional fentanyl-using cohort compared to 38·89 years (SD=10·53) in the non-intentional fentanyl-using cohort. This compared with 32·32 years (SD=9·73) in studies examining intentional fentanyl use only, and 43·34 years (SD=10·34) in studies examining intentional fentanyl use with other substance use.

Regarding gender distribution, studies comparing the two groups reported a mean of 62·52% male participants in the intentional fentanyl-using cohort and 60·54% in the non-intentional fentanyl-using cohort. This compares with 58·93% in studies on intentional fentanyl use only and 63·64% in studies on fentanyl with other substance use. Only one study comparing the two groups directly reported non-binary or gender non-conforming prevalence, which was 37·5% in both the fentanyl using cohort and non-intentional fentanyl using cohort (39). There were no mentions of non-binary or gender nonconformity in the fentanyl use only studies, and one study in the studies on fentanyl with other substance use (31).

Among studies comparing intentional fentanyl using cohorts with non-intentional fentanyl substance using cohorts, individuals who intentionally use fentanyl were more likely to be male and young (17, 23, 28, 40). In Krause et al., 2017, it was reported that a significant difference was found between younger age and fentanyl consumption (p=0·003) (46). In contrast, self-reported unintentional exposure to fentanyl was positively associated with women and older age (40, 49).

Elaborating on racial differences, studies comparing the two cohorts reported a pooled mean of 66·47% participants who were White in the intentional fentanyl cohort and 65·74% participants who were White in the non-intentional fentanyl cohort. This compared with a pooled percentage of 72·43% in studies with intentional fentanyl use only and 62·12% in studies on fentanyl with other substance use. In a study from Baltimore, Boston, and Providence, fentanyl preference was associated with non-Hispanic white race among PWUD (N=308) (32). Similarly, from a case-series that describes buprenorphine/naloxone inductions of four individuals who tested positive for fentanyl, three intentional-using individuals were male and White, while the unintentionally-using individual was female and non-White (14). One study further showed that African American respondents were less likely to report having ever used fentanyl (16). Only one study reported the opposite - that participants preferring drugs containing fentanyl were less likely to be White and non-Hispanic (26).

 Socioeconomic considerations

Among the three groups of studies, each group reported at least one study with either unemployment or educational attainment as a socioeconomic factor. Unemployment was considered as a socioeconomic factor in seven out of 19 studies where intentional fentanyl use and other substance use was not distinguishable ( Table 2 ) (16, 18, 27, 32, 33, 37, 49). The only studies of the 13 that reported on intentional fentanyl use only was a case report that included unemployment as a socioeconomic factor ( Table 3 ) (51). Three of nine studies comparing intentional fentanyl and non-intentional fentanyl using cohorts reported unemployment or illegal work as main source of income as being more common with the intentional fentanyl using group ( Table 4 ) (26, 28, 39).

Educational attainment was reported in eight of 19 studies which did not distinguish fentanyl use and other substance use ( Table 2 ) (16, 18, 21, 27, 31–33, 49). Three studies in the group comparing intentional fentanyl using cohorts with non-intentional fentanyl using cohorts ( Table 4 ) and one study in the intentional fentanyl use only group ( Table 3 ) reported educational attainment as a socioeconomic characteristic (17, 22, 24, 26). In Macmadu et al., 2017, the group of individuals with intentional fentanyl-contaminated heroin use also had a lower proportion who had attained education beyond high school (24).

Among six studies in the group comparing intentional fentanyl using cohorts with non-intentional fentanyl using cohorts, it was reported that individuals who intentionally used fentanyl were more commonly homeless and experiencing unstable housing ( Table 4 ) (17, 23, 24, 28, 39). However only three studies demonstrated this association to be significant (17, 24, 39). Additionally, only three of 19 studies in the group which looked at fentanyl use with other substance use reported the majority of individuals being homeless ( Table 2 ) (31, 32, 35). Homelessness was not reported in any of the 13 studies which examined intentional fentanyl use only ( Table 3 ).

Incarceration and arrest were reported in three of the 19 studies which looked at fentanyl use with other substances ( Table 2 ) (31, 32, 49). Moreover, in the group of studies that compared intentional fentanyl using cohorts with non-intentional fentanyl using cohorts, four studies reported higher rates of incarceration and arrest in cohorts who use fentanyl intentionally ( Table 4 ) (24, 26, 28, 40). However, only two studies found the association to be significant (24, 28). Incarceration and arrest were not reported in the 13 studies that discussed intentional fentanyl use only ( Table 3 ).

 Overdose history

Overdose history was reported in eight of the 19 studies which did not distinguish fentanyl use and other substance use ( Table 2 ) (15, 16, 21, 27, 31, 32, 36, 41). Compared to persons who did not use fentanyl in the prior six months, those that reported fentanyl use were nine times more likely to report a recent overdose following the use of any drug (16). Fentanyl injection and public injection were associated with an increased likelihood of non-fatal overdose (41). Among the group of 13 studies which looked at intentional fentanyl use only, overdose history was reported in six of the 13 studies ( Table 3 ) (20, 34, 42, 50, 51, 53).

Individuals in the studies that compared intentional fentanyl using cohorts with non-intentional fentanyl using cohorts showed that individuals who use fentanyl intentionally experienced more overdoses (reported in seven out of 9 studies) (17, 23, 24, 26, 28, 39, 45). Among people who used heroin or prescription opioids from Baltimore, Boston, and Providence, fentanyl preference was associated with overdose more than a year ago (28). This is in contrast to a study by Chandra et al., 2021 where a cross-sectional survey found that those who purposefully used fentanyl any time in the past were significantly more likely to have experienced an overdose in the past 12 months (17). This finding is also supported by a study on the Australian Needle Syringe Program Survey (45). In British Columbia, Canada, even within the last 6 months, there were higher levels of non-fatal overdose in the last 6 months reported in individuals who intentionally use fentanyl compared to those who do not (39).

 Polysubstance use

By nature of the categorization used in this review, in the group of studies that looked at fentanyl use with other substance use but where fentanyl use data were not distinguishable from other substances, it is implied that these studies included individuals who used other substances ( Table 2 ). Among the group of studies that looked at intentional fentanyl use only, polysubstance use was common among participants as it was reported in nine of the 13 studies ( Table 3 ) (22, 34, 38, 42, 43, 47, 48, 51, 53). This is supported by the group of studies comparing intentional fentanyl using cohorts with non-intentional fentanyl, substance using cohorts, where individuals who intentionally use fentanyl are more likely to report polysubstance use, including cocaine, heroin, and methamphetamine use (reported in eight of 9 studies) (14, 17, 23, 24, 26, 28, 39, 40). In one study, young adults who reported non-medical fentanyl use were associated with regular heroin and cocaine use, diverted pharmaceutical fentanyl use in the prior six months, regular injection drug use and prior overdose, when compared to individuals that reported non-intentional fentanyl-contaminated heroin use (24). Similarly, a population estimation study reported individuals who prefer fentanyl to have recently smoked or injected heroin and more likely to report recent injection of speedball and cocaine (26).

 Reasons for fentanyl use

Among participants from studies on fentanyl with other substance use, five out of 19 studies reported motivations for fentanyl use (13, 27, 33, 37, 44). Motivations included seeking out fentanyl due to their high tolerance levels, (13, 27, 37) higher potency, (13, 27, 33, 37) delaying the onset of withdrawal, (27) and intense rush and feelings of euphoria (13, 44). Among the studies which looked at intentional fentanyl use only, motivations for fentanyl use were reported in six of the 13 studies ( Table 3 ) (22, 38, 47, 48, 50, 51). Motivations included relieving stress/anxiety and pain (22, 38, 51). Among studies that compared intentional fentanyl using cohorts with non-intentional fentanyl substance using cohorts ( Table 4 ), only one study described the motivations for fentanyl use among the sample: among participants who reported intentional fentanyl-contaminated heroin use, the majority (59%) reported that it provided a better high (24).

 Usage patterns

Among the 41 studies included in this review, injection as a route of administration was preferred or common in more than half of the studies. This was reported in 11 of 19 studies which did not distinguish fentanyl use and other substance use. (13, 18, 21, 27, 30–32, 35, 46, 49, 52) Similarly, this was reported in four of 13 studies which looked at intentional fentanyl use only, (22, 34, 38, 53) and seven of the nine studies which differentiated intentional fentanyl using cohorts and non-intentional fentanyl use cohorts. (17, 23, 26, 28, 39, 40, 45) Fentanyl preference was also associated with documented daily illicit drug use, (28) and injection in a public location in the last month, (45) as well as daily injection use. (16)

 Medical comorbidities

Independent correlates of any purposeful fentanyl use included moderate/severe depression. (17) In Macmadu et al., 2017, the group of individuals with intentional fentanyl-contaminated heroin use also had a higher proportion of ever testing positive for HCV and having a mental health diagnosis. (24) Among the studies which looked at intentional fentanyl use only, only 4 had reported concurrent disorders among participants: depression, (51) mental problems, (43) lifetime history of mental illness diagnosis, (22) and depression with psychosis. (34)

 Study quality

Out of the 41 papers included in this systematic review, 19 were cross-sectional studies; three were case-control, cohort, or qualitative studies. Most of the cross-sectional studies were of good methodological quality (a score of 6 or above out of 10). Six were of moderate quality (a score of 5) due to the lack of comparability based on the study design (Supplementary material). All the 12 qualitative studies were of good quality, the only flaw being not considering the relationship between the researcher and the participants for all studies except for one. This systematic review includes 11 case reports, of which nine were of good methodological quality, and two were of low quality. One flaw they all had in common was not including patients’ perspectives or experiences. However, this was not possible for some of the papers as the subjects were deceased ( Supplementary material ).

 Discussion

This systematic review found demographic indicators that were associated with fentanyl use. These include identifying as White, male, and young. Individuals who report intentional use of fentanyl also have higher likelihood of risky substance use behaviours and patterns, such as injection as their preferred route of administration, use of multiple substances, recent overdose history, daily substance use, and use of substances in public spaces. This group was also associated with socioeconomic risks such as homelessness, higher rates of unemployment, and incarceration. The scaling-up of interventions to effectively address such social and structural factors is direly needed to improve the health and well-being of individuals with fentanyl use.

Health care systems currently struggle with adapting treatment strategies to individuals with fentanyl use and severe opioid use disorder (OUD). Some novel approaches to opioid agonist treatment (OAT) have emerged in recent years, but have not seen appropriate and sustainable implementation, despite the need for it. For instance, Health Canada in 2019 approved injectable diacetylmorphine and hydromorphone for treatment of severe OUD in adults (injectable opioid agonist treatment: iOAT), (54) but the number of patients receiving iOAT is still low (149 diacetylmorphine and 28 hydromorphone clients in British Columbia in November 2022) (55). High doses of buprenorphine have been found to be effective in patients who use fentanyl in some studies due to its high potency and affinity for μ-opioid receptors (27, 56). However, the lipophilicity of fentanyl leads to its accumulation in peripheral tissues, resulting in an increased risk of precipitated withdrawal and difficulty with the buprenorphine induction process (57). One such innovation may be the use of low-dose buprenorphine inductions, which has been reported only in case series but has been successfully utilized to avoid precipitated withdrawal among fentanyl-using patients (14, 58). As there is overall limited experience with OAT approaches to suit fentanyl-using individuals, further timely research is needed to explore alternative treatment strategies, which include high-dose methadone and slow-release oral morphine protocols and fentanyl iOAT (59–62).

Current guidelines recommend the use of methadone, buprenorphine, and non-opioids for managing opioid withdrawal, however, these medications can often be insufficient in alleviating withdrawal among patient using fentanyl (63–65). Patients with undertreated withdrawal may use their illicit substances and self-discharge against medical advice, which are strongly associated with adverse outcomes and mortality (66–68). Some physicians have employed the use of short-acting opioids, like IV hydromorphone and fentanyl, to support patients to stay in hospital and initiate them on OAT (60, 65). Although these approaches have been successful, they have not yet been formally recognized as alternatives for withdrawal management in hospitalized patients. Further research is needed to determine the efficacy for these strategies.

This systematic review has several limitations. Of note are the heterogeneity of the included studies. In particular, it was important for this study to identify and focus on the intentionality of fentanyl use. Therefore, other variability was accepted in the inclusion criteria. In order to present data as granular as possible, studies where fentanyl use specifically was separated from other substances were grouped separately from studies where fentanyl use was included but not separable from the use of other substances. In addition, due to the novelty of this paper, and its focus on qualitative outcomes and breadth of data, it was difficult to screen for sufficient homogeneity to allow for a meta-analysis. Finally, this review specifically reported on intentional non-medical fentanyl use among PWUD, as opposed to among people with OUD, in order to increase the breadth of studies included and the generalizability of the findings.

 Conclusion

The growing tendency to use fentanyl as drug of choice is extremely concerning. Our review has found that individuals who intentionally use fentanyl have severe substance use patterns, precarious living situations, and extensive overdose histories. With the street supply of opioids increasing in toxicity and an increasing number of individuals intentionally seeking fentanyl, more effective withdrawal management and OAT approaches must be developed. This paper calls for healthcare providers, researchers, and government advocates to develop alternative approaches for OUD and put in place policies allowing increased availability for fentanyl-based treatment options based on further research, which will result in a paradigm shift in the system of care.

 Data availability statement

The original contributions presented in the study are included in the article/ Supplementary Materials , further inquiries can be directed to the corresponding author.

 Author contributions

VT: Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing. JW: Data curation, Formal Analysis, Methodology, Writing – original draft, Writing – review & editing. JWe: Data curation, Formal analysis, Methodology, Writing – original draft, Writing – review & editing. NR: Data curation, Formal analysis, Writing – review & editing. HF: Data curation, Formal analysis, Writing – review & editing. MN: Writing – review & editing. VL: Writing – review & editing. NM: Writing – review & editing. PA: Writing – review & editing. KJ: Writing – review & editing. RK: Conceptualization, Resources, Supervision, Writing – review & editing.

 Funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

 Acknowledgments

The authorship team would like to thank members of the research team including Rachael Reinders for her work on this manuscript. The team would also like to thank the patients at affiliated hospitals for their inspiration and motivation to carry out this project and advocate for improvements to the current health system.

 Conflict of interest

PA is a consultant on Indivior-led buprenorphine extended-release studies, which are unrelated to this systematic review.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.

 Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

 Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1347678/full#supplementary-material

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