“Whatever it is, it Works” Understanding of Buprenorphine/Naloxone and Sources of Information: A Qualitative Study Among People Who Use Fentanyl and Clinicians

Abstract

Objectives:

Most persons with opioid use disorder (OUD) are not receiving effective treatment with medications. A lack of understanding and misinformation may impede an individual’s decision to begin or continue medications for OUD (MOUD). This study explored the understanding of the role of naloxone, and sources of information related to buprenorphine/naloxone products among people who use fentanyl (PWUF) and clinicians.

Methods:

Qualitative study utilizing semi-structured interviews with PWUF and clinicians providing buprenorphine care. Participants were recruited via flyers and word of mouth (PWUF), and direct emails (clinicians). Interviews were audio recorded, transcribed, and analyzed using a rapid qualitative analysis process, which consists of creating templated summaries separated by domains to formulate themes.

Results:

Forty-three adults (28 PWUF and 15 clinicians) from Seattle, WA, participated in interviews between April and November 2024. The analyses identified 3 themes: (1) PWUF and clinicians both acknowledge confusion around how buprenorphine and naloxone work; (2) misconceptions may lead to adverse events, anxiety, and/or lack of interest in starting buprenorphine, especially in the setting of fentanyl use; (3) while PWUF had high regards for clinicians, the primary and most trusted source of information is people with lived experience taking buprenorphine/naloxone.

Conclusions:

Findings suggest confusion and lack of information about the role of naloxone in buprenorphine/naloxone, potentially limiting medication uptake. The finding that patients mainly hear about buprenorphine/naloxone from people with lived experience should be incorporated into outreach strategies. Future efforts should increase involvement from people with lived experience taking buprenorphine in disseminating accurate information regarding MOUD.

As opioids continue to cause excessive morbidity and mortality in the United States, optimal implementation of medications for opioid use disorder (MOUD) is an emerging area of research. Despite evidence of its effectiveness, buprenorphine is underused by people who could benefit from the medication. In a national cohort study of over 150,000 individuals, only 20% received buprenorphine within 180 days of an OUD-related health event.¹ In a Seattle, Washington area survey of people with OUD, where the current study was focused, ∼20% of participants reported receiving buprenorphine treatment in the past year, and nearly half reported receiving no MOUD.² There are multiple documented barriers to starting buprenorphine, including stigma, insurance issues, and a lack of available clinicians.³

A reported barrier, which is not well understood, is a lack of understanding of buprenorphine-containing product pharmacology among both patients and clinicians.^4–7 This is important because buprenorphine’s pharmacology is different from other opioids, and misinformation could lead to adverse events. Buprenorphine works as a partial agonist on the mu opioid receptor. This agonism leads to stimulation of the receptor and a decrease in cravings and withdrawal symptoms, a concept of “narcotic blockade” initially described by Dole and colleagues in their 1966 paper on methadone.⁸ Buprenorphine also has a high affinity for the mu opioid receptor and if taken too soon after using a full agonist opioid can displace that full-agonist, potentially causing sudden severe withdrawal, termed “precipitated withdrawal.”^9,10

Buprenorphine is often co-formulated with naloxone (ie, Suboxone, Indivior Inc., North Chesterfield, VA), which was added as a misuse deterrent and is believed to have minimal bioavailability or systemic absorption when taken as directed (ie, sublingually).¹¹ However, if injected or inhaled, the naloxone becomes bioavailable and will act as an antagonist, which may lead to precipitated withdrawal in the setting of recent opioid use, and block euphoria. Lastly, fentanyl, now the most common opioid involved in overdose deaths, makes this pharmacology more complex.¹² Fentanyl is highly lipophilic and may persist well beyond when an individual stops using it, potentially making precipitated withdrawal more likely when starting buprenorphine/naloxone.^13,14

To design optimal buprenorphine initiation protocols for people using fentanyl (PWUF), a better understanding of how patient and clinician knowledge of these properties impacts medication decisions, and how clinicians educate and respond to potential misinformation, is needed. The current study aims to explore how PWUF and clinicians understand the components of buprenorphine/naloxone, how misinformation may impact treatment decisions, and sources of information.

METHODS

This is a secondary analysis of data collected during a qualitative study focused on experiences starting buprenorphine in the context of fentanyl use. The parent study was conducted by the same research team and included the same participants. In the present analysis, we focus on participants’ understandings of how buprenorphine/naloxone works, and where PWUF obtain buprenorphine-related information that shapes their expectations. The current qualitative study was reviewed by the Institutional Review Board (IRB) of the University of Washington and deemed exempt (IRB ID #00017673). All procedures were in accordance with the Helsinki Declaration.

Inclusion/Exclusion Criteria

Individuals were eligible if they were 18 years old and proficient in English. PWUF were eligible if they reported initiating buprenorphine in the setting of fentanyl within the last 6 months, regardless of whether they remained on it. Clinicians (physicians, nurse practitioners, registered nurses) were eligible if they reported providing care to PWUF when they started buprenorphine in the past 6 months.

Recruitment

PWUF were recruited via flyers posted in primary care and mental health clinical spaces from a single health care system, discussions with buprenorphine clinicians to identify possible participants, and snowball sampling from participants. Clinician participants were identified by the study staff and recruited via direct email. Clinicians were recruited from primary care and addiction specialty clinics from a single academic health care system, and also from community settings. We purposely recruited clinicians with significant experience starting buprenorphine for OUD. All participants took part in a semi-structured interview. PWUF were compensated with $40 cash. Clinicians had the option of receiving $40 cash or a $40 online gift card.

Data Collection

PWUF were interviewed in-person, and clinicians had the option of a Zoom interview. Interviews were audio recorded and professionally transcribed using secure online software (MAXQDA).¹⁵ Participants completed a self-report demographic questionnaire that was in accordance with the National Institute of Health, and entered into REDCap (Appendix 1, Supplemental Digital Content 1, http://links.lww.com/JAM/A755).^16,17

The interview guide (Appendix 2, Supplemental Digital Content 2, http://links.lww.com/JAM/A756) was developed based on a literature review conducted by the research team, and in consultation with clinical and qualitative research experts and a peer support specialist (a person with lived experience of substance use, who received training and certification to provide support for others). Interview questions were grouped into 5 domains: decision-making process and sources of information related to MOUD, buprenorphine initiation logistics and experience, barriers and facilitators to starting buprenorphine, and insights and observations about treatment setting and clinicians. PWUF were asked about their overall substance use history, and clinicians were asked about their experience offering buprenorphine. Each domain included open-ended questions, and follow-up probes. Interviews were conducted by 2 members of the research team: a physician and researcher trained in internal and addiction medicine who prescribes buprenorphine frequently (EB) and a research coordinator with a master’s level research psychology background (OG). The research team had no relationship with study participants before the study commencement. Data collection was concluded once 45 interviews were conducted, and thematic saturation was reached.

Data Analysis

Demographic information was analyzed descriptively. The qualitative analysis focused on questions related to MOUD understanding and sources of information for buprenorphine. Specifically, we analyzed the data that emerged from the questions: “How might you explain how buprenorphine works to someone who doesn’t know?”, “What (if anything) have you heard about naloxone being in the buprenorphine medications?”, “Tell me about where you look, or who you talk with when looking for information about buprenorphine.” We also included information related to these topics if they came up in other areas of the interview.

Two researchers independently reviewed each transcript generated by MAXQDA¹⁵ and removed any potential identifiers. A rapid analysis process (RAP)¹⁸ was used to create templated summaries of each transcript, organized by separate rows for each domain, and columns for key points and quotes. A deductive approach generated the initial set of domains, with inductive work adding additional domains as transcripts were analyzed. Once separated by domains, the summaries were combined into a matrix document in Excel. Separate matrix documents were created for PWUF and clinicians. Each matrix document had separate tabs for each domain. Two researchers printed out the matrices and used color-coding to identify commonalities among the domain summaries to formulate emerging themes. A summary document was used to keep track of themes and was shared with the larger research group for feedback in an iterative process.

RESULTS

Between April 2024 and November 2024, we interviewed 45 participants. Our final analytic sample consisted of 43 participants (28 PWUF and 15 clinicians). One PWUF participant was excluded because they were determined during the interview to not meet the study criteria of taking buprenorphine within 6 months, and one was excluded because of technical difficulties with the audio recording. Interviews typically lasted between 45 and 60 minutes.

PWUF had a mean age of 44, with a range of 24–64; most PWUF identified as male (18/28, 64.3%), and just under half identified as White (13/28, 46.4%). Clinicians had a mean age of 40, with a range of 33–49; most clinicians identified as male (8/15, 53.3%) and White (14/15, 93.3%). Clinicians had been prescribing and/or providing buprenorphine care for an average of 6.8 years, with a range of 2–12 years. Additional demographics are presented in Tables 1 and 2. Emerging themes were reviewed concurrently during data collection until a similar pattern of themes was continually found across the matrix document. After reaching thematic saturation among PWUF and clinicians, 3 main themes emerged.

TABLE 1.

Descriptive Characteristics of the Clinician Participants

Characteristic	No. (%)
Age, mean (SD), y	39.9 (5.3)
Age range, y	33–49
Gender identity
Male	8 (53.3)
Female	7 (46.7)
Race/ethnicity
White	14 (93.3)
Other	1 (6.7)
Type of degree
Doctor of medicine	8 (53.3)
Registered nurse	5 (33.3)
Nurse practitioner	1 (6.7)
Not reported	1 (6.7)
Years of prescribing/providing buprenorphine care, mean (SD)	6.8 (2.8)
Years of prescribing/providing buprenorphine care, range	2–12
Primary practice setting
Outpatient clinic	11 (73.3)
Inpatient	1 (6.7)
Emergency department	1 (6.7)
Outpatient, supportive housing	1 (6.7)
Other	1 (6.7)

TABLE 2.

Descriptive Characteristics of the Study Participants Who Use Fentanyl

Characteristic	No. (%)
Age, mean (SD), y	43.8 (10.9)
Age range, y	24–64
Gender identity
Male	18 (64.3)
Female	9 (32.1)
Other	1 (3.6)
Race/ethnicity*
White	13 (46.4)
Black/African American	9 (32.1)
Hispanic/Latino	5 (17.9)
American Indian/Alaska Native	2 (7.1)
Asian	1 (3.6)
Native Hawaiian/Pacific Islander	1 (3.6)
Other	1 (3.6)
Level of education
Middle school or less	1 (3.6)
Some high school, no diploma	3 (10.7)
High school diploma or GED	15 (53.6)
Some education after high school, no degree or certificate	4 (14.3)
Associate’s degree or vocational degree	2 (7.1)
4-year college degree (BA/BS)	2 (7.1)
Master’s degree	1 (3.6)
Living arrangement*
Own/rent home	9 (32.1)
On the street(s) without shelter	6 (21.4)
Residential addiction program	5 (17.9)
Shelter	5 (17.9)
Staying with family member(s)	4 (14.3)
Staying with friend(s)/other non-relatives	1 (3.6)
Access to cell phone
Yes	22 (78.6)
No	6 (21.4)
Times started buprenorphine (past 3 y)
1	8 (28.6)
2–5	13 (46.4)
> 5	7 (25)
Times needed Narcan to treat an overdose (past 3 y)
0 times	13 (46.4)
1–5 times	13 (46.4)
> 5 times	2 (7.1)

^*Some participants chose more than one response option.

Theme 1: PWUF and clinicians both acknowledge confusion around how buprenorphine and naloxone work.

Most PWUF referred to buprenorphine/naloxone by a brand name “Suboxone,” and were less familiar with the generic names of the components. “I don’t know…I only know Suboxone. Not the naloxone.” (P32, other, age 51). Some PWUF participants were unaware of the naloxone component of buprenorphine/naloxone until participating in the qualitative interview. “I’m not sure what naloxone is.” (P42, female, age 40) or “Those are medical terms I don’t understand.” (P24, female, age 54)

When asked how buprenorphine/naloxone works, nearly all PWUF believed it acts as a “blocker.” Some were able to elaborate, such as in this description from a PWUF, “It attaches to the receivers in your brain or whatever that would normally receive the fentanyl and the pain relief or whatever. And then it replaces it with the Suboxone, and it keeps you feeling like you have something there without a total shock to your body.” (P47, male, age 27)

However, there was confusion when PWUF were asked about the separate buprenorphine and naloxone components. “That one is an opiate, and the other is a blocker. So, I always wondered, I’m like how do they put those two together without activating like that? But whatever it is, it works.” (P31, male, age 39)

PWUF often thought the naloxone component acted as the primary “blocker” rather than the buprenorphine. When asked if they knew why the naloxone is a part of the medication, one PWUF answered, “Yeah, I mean just to make it so that you are unable to, like, achieve a high” (P23, male, unknown age). In this way, the blocking effect of the naloxone component was seen by PWUF as a positive, in that there was blockade of opioid effect and cravings. We also heard an array of mixed feelings regarding the naloxone component, often as patients tied it to experiences or knowledge of naloxone formulations for treatment of overdose.

“I don’t mind it, you know, but I guess I don’t really understand, like, why they put it in there. Because, like, naloxone, as far as I know, is like, really just used for, like, bringing people out of, like, ODs.” (P18, male, age 33)

“I mean Narcan scares me. It’s not a nice drug. Yeah, but obviously it saved my life. But it’s not a nice drug. It makes you feel awful. (…) They’ve explained to me it blocks the receptors so that if I was, while I’m on Suboxone and (…) if I was to go do some fentanyl, that. I would just get sick.” (P12, male, age 39)

And several related the naloxone directly to feelings of withdrawal when starting on combination products. “I don’t know much about the naloxone part to tell you the truth. All I know is it’s just part of the reason why I get withdrawal.” (P37, male, age 54).

Clinicians acknowledged the naloxone component as being difficult for both patients and clinicians to understand. One clinician said, “The most, like the biggest misconception I hear from patients and this has been the entire time I’ve been here, is that I don’t know what … they think the buprenorphine is actually doing, but they think the naloxone is what’s blocking the whatever that is being used. And so (…) that’s a con (…) I think I’ve heard health care providers say that before.” (P10, female, age 43)

Some clinicians reported either struggling to correct or not feeling the need to correct misinformation around the naloxone component unless it was harmful. One clinician said, “I think that more often than not, patients don’t understand the biomechanics of what the naloxone is doing or not doing. (…) I won’t go to great lengths to correct people unless it’s harmful. So, like, there’s people who are like, oh yeah, it’ll, that’s what’s stopping the overdose. And I’m like, not really, but all right. And then there’s people who are like, the naloxone is like what causes precipitated withdrawal. And I’m like, no, please don’t tell your friends that. Like, that’s not, that’s not what’s happening. (…) I mean, it’s hard for me to even understand how it works.” (P3, female, age 34)

Another clinician shared, “I was just describing this to a resident who I was working with the other day, that once people have the, the assessment that the naloxone component is bad and that it is not compatible with them, there is no way around it. You can coach and coach as much as you want, but you are not going to persuade them that this is actually safe for them to take.” (P35, male, age 35)

Theme 2: Misconceptions may lead to anxiety and/or lack of interest in starting buprenorphine/naloxone, especially in the setting of fentanyl use.

PWUF reported confusion about how long to wait before taking buprenorphine/naloxone after fentanyl use, which led to individuals not starting buprenorphine: “You gotta wait nine days to take this pill. I mean that’s a long time. You’re sick. So I said no. Because you know, fentanyl, you took four hours. It wears off, man.” (P9, male, age 55) or feeling uncertain about the timing: “Well, I mean, the nurse had said you don’t need to deal with it a couple of days, but somebody tells me something different every time with, with that, like, the doctor always tells me that it can’t be within like eight hours. The nurse tells me it can’t be within like two days. And then like, I don’t I really don’t know what it is.” (P45, male, age 34)

Some PWUF had misconceptions about the different buprenorphine formulations that led to adverse events, including precipitated withdrawal. “I was told that Subutex [buprenorphine mono-product] wouldn’t send you into precipitated withdrawal. Maybe it wasn’t Subutex, or maybe that was misinformation, one or the other. Whatever it was, I actually shot it and it was like as soon as I shot it, I knew that I made a mistake because it came on immediately. Like I said, precipitated withdrawal. It was like within 30 seconds. I started to just feel, like, horrible.” (P26, male, age 43)

There were also PWUF participants that viewed the idea of taking buprenorphine/naloxone in the setting of fentanyl use as dangerous and even deadly. “Because yeah, with the other one [naloxone] that Suboxone has, that’s the, if you get high that could get you sicker than shit and could kill you.” (P43, male, age 64). When asked about continuing to use fentanyl while you are taking buprenorphine, another PWUF participant said, “I think it’s dangerous. Super dangerous.” (P22, female, age 43)

We heard skepticism from PWUF that buprenorphine/naloxone would be effective for people using fentanyl, because fentanyl is so potent. “Well, I know that the, the fentanyl nowadays is strong enough that it breaks through that, because I know a lot of people said that the reason that they like Suboxone is because it’s also a blocker. So even if even if you were to get cravings while you were on it, the blocker makes it pointless. But the fentanyl is so strong now that it actually breaks through that barrier.” (P26, male, age 43)

Clinicians reported hearing rumors and misconceptions about buprenorphine/naloxone from PWUF, specifically in the setting of fentanyl use. “There’s so many rumors in the community among my patients, you know, rumors about, like, well, buprenorphine doesn’t work for fentanyl.” (P28, female, age 44)

Another clinician said, “I do sometimes hear from people that they were told it [buprenorphine] just won’t work with fentanyl, like it’s just not going to work. So, they’ve been reluctant to try it because they’ve heard that from friends.” (P34, male, age 43)

Theme 3: While PWUF had high regard for clinicians, the primary and most trusted source of information is people with lived experience taking buprenorphine/naloxone.

PWUF reported a few different sources of information for buprenorphine/naloxone, with community members and people with lived experience being the most common source of information. “I think a lot of information comes from the actual people using it, because I remember, I never, (…) no doctor told me about precipitated withdrawals. I had heard it 150,000 times from people on the street before I ever heard a medical professional warn me against it.” (P25, male, age 47)

Some PWUF did seem to value the information given by healthcare clinicians but often reported not being able to remember specific instructions on starting buprenorphine given by clinicians, and the instructions being too complicated. “I think the language is a bit confusing for people.” (P39, female, age 36)

Clinicians shared the opinion that PWUF get most of their information about buprenorphine and fentanyl from community members and friends. “It’s usually kind of a community, almost resource gathering and data gathering from the community.” (P6, female, age 33)

Clinicians placed an emphasis on peer support specialists providing valuable information to individuals starting buprenorphine/naloxone. “People who are already on it, ideally peers or someone like that would be an ideal situation, who has access to a prescriber and access to, you know, if patients need more support medication wise or anything like that. So, but ideally someone who’s been through it themselves, with fentanyl.” (P38, male, age 39)

Another provider stated, “Our peer [peer support specialist] is amazing. Care navigators, top of the line in terms of organizational skills. I think it’s just a high performing team that is really motivated to just care for the patients.” (P36, male, age 41)

DISCUSSION

These findings suggest a lack of information and confusion among PWUF related to how buprenorphine/naloxone works. Clinicians are aware of these beliefs, but generally did not feel it was effective or necessary to spend time correcting their patients on this topic. Some PWUF reported misconceptions resulting in anxiety and reluctance around taking buprenorphine/naloxone products. Both clinicians and PWUF agreed that peers and community members were the best sources of information.

Studies of medication nonadherence across multiple chronic diseases show that beliefs about medication necessity and potential side effects explain a significant amount of adherence variability.^19,20 The findings in our study add to qualitative literature demonstrating that medication knowledge and understanding are important factors for decisions on MOUD. For example, although current literature shows mixed findings around the prevalence of precipitated withdrawal, the perception that it is common has impacted PWUF and led to increased anxiety around starting buprenorphine/naloxone.^10,21 In the current study, PWUF ascribed their primary concerns to the naloxone component of buprenorphine/naloxone and reported naloxone to cause withdrawal. These results highlight how inaccurate information might amplify concerns and impede the uptake of buprenorphine/naloxone, especially when there is a growing concern of precipitated withdrawal in the setting of fentanyl use.²¹

Clinicians reported that PWUF often identify the naloxone component of buprenorphine/naloxone as a “blocker.” Although clinicians were aware of patient beliefs around the naloxone component of buprenorphine/naloxone, some clinicians reported only correcting misinformation if it seemed harmful, which generally they did not endorse. Offering education to PWUF on how this medication works and why withdrawal can occur may have the benefit of reduced anxiety and increased confidence around starting buprenorphine/naloxone and counter the spread of misinformation, which may be a deterrent to engagement in treatment.

In the current study, there was a strong consensus among both PWUF and clinicians that the most meaningful information came from friends and family with previous experiences. A previous study by Zuccarini and Stiller²² supports this sentiment, showing that individuals who interacted with peer-support services had increased engagement with medication-assisted treatments, in comparison to a control group. Thus, the use of peer support specialists would be a powerful tool to help PWUF understand instructions and prevent the accidental spread of misinformation.

There are several limitations to this study. All participants in the study were recruited from the Seattle area, and due to variability in clinical practice and individual experiences in different geographic regions, these results are not intended to be widely generalizable. In addition, the clinicians from this study have significant experience prescribing buprenorphine and may not represent all clinicians who prescribe buprenorphine. However, the information gained from this study should be used to inform future research and practice. We also relied on self-reported information from participants; thus, participants may not have shared certain opinions or experiences due to social desirability bias and memory recall issues. Lastly, it is worth acknowledging that emerging evidence calls to question the assumption that naloxone absorption is negligible, calling for the field to further examine the usefulness of the naloxone component.^23,24

CONCLUSION

This qualitative analysis revealed that many PWUF have misconceptions around the effects of the separate components of buprenorphine/naloxone combination products. Clinicians should assess the knowledge and understanding among PWUF and address confusion about how the components of buprenorphine/naloxone work. Specifically, having a supportive and trusting patient-clinician relationship may play an essential role in dispelling misconceptions around buprenorphine/naloxone. Furthermore, due to the high value placed on learning from people with previous experience, peer support specialists should be included in interventions to spread awareness and information about MOUDs. Future studies should conduct clinical trials to examine how buprenorphine/naloxone uptake is impacted by addressing misunderstandings and using peer support services.

Supplementary Material

adm-20-532-s001.pdf ^{(41.5KB, pdf)}

adm-20-532-s002.docx ^{(42.9KB, docx)}