Implementation of Low-Dose Buprenorphine Induction at a Syringe Services Program: A Pilot Study

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Hauschild, Peyton V Warp, William H Eger, Ryan Hood, Monica Bahamon, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7160434/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Apr, 2026 Read the published version in Addiction Science & Clinical Practice → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Fentanyl’s penetration into the unregulated drug supply has complicated the treatment of opioid use disorder (OUD), particularly by increasing the risk of buprenorphine-precipitated opioid withdrawal (BPOW). Buprenorphine, a partial opioid agonist, remains a first-line treatment for OUD, but traditional induction methods can be intolerable for people using fentanyl. Low-dose induction (LDI), a strategy characterized by gradual buprenorphine titration without prior withdrawal, has emerged as a promising alternative to mitigate BPOW. However, the feasibility and acceptability of LDI in low-barrier, real-world settings such as syringe services programs (SSPs) remain underexplored. Methods: We conducted a mixed-methods prospective cohort study from June 2023–2024 at an SSP in Miami, Florida, offering a 4-day LDI protocol to patients with OUD who were interested in starting buprenorphine. Follow-up, conducted on a walk-in basis within four weeks, included urine drug screens (UDS), symptom surveys and semi-structured qualitative interviews. The primary outcome was successful buprenorphine initiation, defined by a positive UDS for buprenorphine at follow-up. Results: Of the 30 participants enrolled in the 4-day LDI protocol, most (n=29) had prior buprenorphine experience and nearly 90% (n=26) reported past BPOW. Only 16 (53%) returned for follow-up. Nine (56%) of those followed up tested positive for buprenorphine, 11 (68.8%) reported that LDI worked for them, and 12 (75%) said they would use the method again. Qualitative interviews revealed six key themes: 1) LDI mitigates withdrawal symptoms; 2) instructions were helpful but could be improved; 3) fear of BPOW motivated LDI use; 4) LDI enabled autonomy in recovery; 5) unstable living environments hindered adherence; and 6) LDI allowed participants to maintain social roles. Conclusions: While only 30% of the cohort had objective evidence of buprenorphine induction, most reported successful attempts and found LDI acceptable and empowering. High loss to follow-up and environmental instability limited our conclusions in this outpatient harm reduction setting. These findings underscore the potential of LDI to reduce barriers to buprenorphine use, especially when adapted to real-world constraints. Further research is needed to refine LDI protocols and address the structural determinants affecting treatment success among people who use fentanyl. addiction opioid use disorder fentanyl buprenorphine low-dose induction microdose Figures Figure 1 Figure 2 Background Illicitly manufactured fentanyl exacerbated the national overdose crisis when it replaced heroin as the dominant opioid in several major illicit drug markets in North America in the second decade of the 21st century. 1 While national drug overdose rates began to decline in 2023 for the first time since 2018, there were still greater than 48,000 overdose deaths related to fentanyl in 2024. 2 Safe and effective medications for opioid use disorder (MOUD), including the partial opioid agonist buprenorphine, have resulted in reductions in overdose and serious opioid-related acute care use. 3 Beyond systemic barriers to treatment, people with opioid use disorder (OUD) face the risk of buprenorphine-precipitated opioid withdrawal (BPOW). BPOW is a phenomenon in which opioid withdrawal symptoms are paradoxically worsened by the initiation of buprenorphine due to its activity as a high-affinity partial-agonist at the mu-opioid receptor. The lipophilicity of fentanyl, which prolongs tissue retention, increases the intensity of BPOW and necessitates the urgent need for new ways to initiate buprenorphine in the fentanyl era. Multilevel challenges to starting buprenorphine contribute to low treatment initiation and retention as well as high mortality among people with OUD, especially in the context of high fentanyl adulteration in unregulated opioid supplies. 4 The American Society of Addiction Medicine’s clinical practice guidelines favor waiting until patients experience objective signs of opioid withdrawal before taking the first dose of buprenorphine to avoid BPOW. 5 Under this model, nausea, vomiting, diarrhea, anxiety and pain are expected. Despite these recommendations, up to 45% of patients who initiate buprenorphine after fentanyl use report severe worsening of withdrawal symptoms with buprenorphine. 6 An alternative approach, often referred to as microdose-induction or low-dose induction (LDI), has emerged to remove the withdrawal prerequisite for buprenorphine initiation. LDI involves administering small escalating doses of buprenorphine prior to development of severe withdrawal symptoms to minimize the risk of BPOW. 7 The efficacy of LDI, particularly for individuals averse to withdrawal or using fentanyl, has been demonstrated in inpatient settings with close clinical supervision. 8 While case reports have suggested the feasibility and success of LDI in outpatient substance use disorder clinics, 9 a larger study by Suen et al. found only 34% of people using an LDI protocol successfully initiated buprenorphine in the outpatient setting. 10 While various LDI protocols are well-documented, 9 , 11 , 12 there remains a critical need to determine best practices for LDI implementation in low-barrier harm reduction settings, like syringe services programs (SSPs), to increase buprenorphine uptake and retention for the most vulnerable patients, including those experiencing homelessness. To address this gap, we adapted a 4-day LDI treatment protocol and began offering patients the LDI buprenorphine initiation at an SSP in Miami, Florida. 13 , 14 In this mixed-methods pilot study, we aimed to evaluate the preliminary clinical outcomes of LDI for initiating buprenorphine while examining implementation outcomes (e.g., feasibility, acceptability) in a real-world harm reduction setting. 15 Methods Study Design and Setting We conducted a prospective cohort study from June 2023 to June 2024 of patients with a diagnosis of moderate to severe OUD per the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) seeking buprenorphine from their local SSP (IDEA Miami). The SSP provides harm reduction services, wound care, and substance use disorder treatment services, including buprenorphine for OUD, to individuals regardless of insurance status. 13 The Institutional Review Board at the University of Miami approved this study (UM IRB #20230483) and written informed consent was obtained from participants. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines were followed. Recruitment and Data Collection Eligible participants were adults aged 18 years or older with moderate to severe OUD who tested negative for buprenorphine by urine drug screen (UDS) while presenting for buprenorphine induction. Individuals interested in participating provided written informed consent and met with a clinician to review their substance use history and goals for treatment. Participants were presented with options for buprenorphine initiation, including LDI and traditional initiation, as well as referral to methadone treatment. For participants who completed the informed consent process, physicians provided counseling on the 4-day LDI protocol and an instructional handout (Fig. 1 ). 16 , 17 Prescriptions for buprenorphine and medications to alleviate any withdrawal symptoms were sent to an affiliated outpatient pharmacy. Results of a 13-panel UDS, in addition to xylazine testing results were also recorded. Besides the UDS results, all data collected were self-reported; at the conclusion of the initial clinical visit, participants completed an interviewer-administered baseline survey assessing demographic characteristics and prior experiences with buprenorphine. In the survey, participants rated withdrawal symptoms associated with past buprenorphine induction experiences on a scale of mild to severe. Participants were compensated $ 10 for completion of the initial study visit. Participants were asked to return to the clinic within four weeks for follow-up procedures. At the follow-up visit, a UDS, a survey about participants’ withdrawal symptoms and semi-structured qualitative interviews were completed for each participant. All interviews took place in person in a confidential space and were conducted by trained student researchers. Interviews were audio-recorded, professionally transcribed and reviewed by the research team for accuracy. Participants received an additional $ 10 for completing all follow-up procedures. Outcomes of Interest The primary outcome was successful buprenorphine initiation, defined as having a UDS positive for buprenorphine at the follow-up visit. Treatment success is presented for those who attended a follow-up visit as well as for the whole cohort, where loss to follow-up was considered unsuccessful treatment. Data Analyses Descriptive statistics are presented as percentages for categorical variables and medians and interquartile ranges for continuous variables. Analyses were completed using Microsoft Excel (Version 16.96). Our qualitative analysis process for follow-up interviews followed an “open-coding” process informed by the Capability, Opportunity, Motivation, and Behavior (COM-B) framework. Structuring thematic analysis around the COM-B components allowed researchers to systematically identify barriers and facilitators to behavior change as reported by participants, allowing inductive themes to emerge from the data. COM-B was chosen for its structured approach to developing targeted interventions, which involves evaluating individuals’ capability, motivation, and opportunity to engage in a specific behavior, while accounting for the broader contextual factors that influence change. 18 Three graduate-level qualitative analysts (MHH, PVW, WHE) first read small batches of transcripts to gain a broad understanding of topics covered and to develop a series of memos to clarify emergent ideas and dominant COM-B constructs. Qualitative memos were developed for approximately one-third of transcripts to ensure no additional inductive ideas were present and to develop a preliminary codebook. After development of the preliminary codebook, which included specific inclusion and exclusion criteria, two team members met biweekly to address discrepancies in their independent coding process and to further refine the codebook until coding consensus —defined as consistent application of the codes to transcripts—was established. Coding consensus was achieved after approximately 20% of transcripts were double-coded and reviewed through consensus discussions. A third analyst was consulted in the rare instances where consensus could not be reached between the initial coders. Once all transcript data was coded, the coded passages were read by all three qualitative analysts to identify themes. The team refined the final themes through discussions with the rest of the research team, which are presented below. All coding was completed using NVivo 14 (QSR International Pty Ltd, 2020). Results Baseline Characteristics From June 2023 to June 2024, 45 participants presenting to the SSP to start buprenorphine were approached for enrollment in the study. Thirty participants seeking LDI buprenorphine initiation were enrolled (median age = 35, 53% male). Nearly half of participants self-reported being unhoused (47%) and a hepatitis C diagnosis (47%), and 37% reported a post-traumatic stress disorder diagnosis (Table 1 ). UDS results at baseline were 97% positive for fentanyl, 76% for cocaine, and 64% for xylazine. Table 1 Participant Demographics and Health Characteristics at Baseline and Follow-Up Baseline (N = 30) Follow-Up (N = 16) Variable N (%) N (%) Age (median, Q1–Q4) 35 (32–40) 35 (30.5–39) Gender Man 16 (53.3%) 11 (68.8%) Woman 14 (46.7%) 5 (31.3%) Race/Ethnicity White non-Hispanic 16 (53%) 8 (50%) White Hispanic 12 (40%) 7 (43.8%) Black Hispanic 1 (3%) 1 (6.3%) Native American 1 (3%) 0 (0%) Housing Status Apartment/House 16 (53.3%) 8 (50%) Unhoused 14 (46.7%) 8 (50%) Street/camping/squatting 9 (64.3%) 5 (31.3%) 3 (18.8%) Couch surfing 5 (35.7%) 3 (18.8%) Educational Attainment Graduated high school 24 (80%) 12 (75%) Did not graduate high school 6 (20%) 4 (25%) Smokes Tobacco Yes 25 (83.3%) 13 (81.3%) No 5 (16.7%) 3 (18.8%) Employment Status* Unemployed 20 (66.7%) 11 (68.8%) Employed 7 (23.3%) 3 (18.8%) Unable to work 2 (6.7%) 1 (6.3%) Lifetime Diagnoses (self-report) Hepatitis C 14 (46.7%) 8 (50%) PTSD 11 (36.7%) 5 (31.3%) Generalized anxiety disorder 10 (33.3%) 4 (25%) Major depressive disorder 10 (33.3%) 4 (25%) ADHD 8 (26.7%) 3 (18.8%) Asthma 6 (20%) 4 (25%) Bipolar disorder 5 (16.7%) 2 (12.5%) Chronic wounds/ulcers 5 (16.7%) 3 (18.8%) HIV 0 (0%) 0 (0%) UDS Results at Baseline Fentanyl 29 (96.7%) 13 (81.3%) Cocaine 22 (73.3%) 12 (75%) Buprenorphine 0 (0%) 9 (56%) Xylazine** 18 (64.3%) 4 (25%) MDMA 11 (36.7%) 7 (43.8%) Cannabis 10 (33.3%) 7 (43.8%) Benzodiazepines 8 (26.7%) 6 (37.5%) Amphetamine 5 (16.7%) 2 (12.5%) Opiates 5 (16.7%) 7 (43.8%) Ethyl glucuronide 4 (13.3%) 2 (12.5%) Methamphetamines 4 (13.3%) 2 (12.5%) Methadone 2 (6.7%) 0 (0%) Oxycodone 0 (0%) 1 (6.3%) Barbiturates 0 (0%) 0 (0%) *One participant did not respond to this question in the baseline survey **28 participants were tested for xylazine. Most participants (80%) reported previous buprenorphine treatment experience and fewer than 5 lifetime induction attempts (79%) (Table 2 ). Ninety percent (90%) reported ever experiencing BPOW in the past. The most reported severe symptoms of opioid withdrawal were anxiety (83%), bone/joint pain (73%), sweating (70%) and insomnia (70%). Over half reported experiencing severe nausea (63%), runny nose (63%), mood change (60%), vomiting (53%), and shakes/tremor (53%) (Table 2 ). Before study enrollment, fewer than half (43%) of participants were familiar with LDI and 20% had previously attempted to use an LDI method (Table 2 ). Table 2 Experiences with Buprenorphine At Baseline (N = 30) After LDI (N = 16) Variable N (%) N (%) Previous buprenorphine induction attempts ≤ 5 attempts 23 (79.3%) > 5 attempts 6 (20.7%) Previous buprenorphine treatment duration 24 (80%) Duration* ≤ 1 year 14 (60.9%) >1 year 9 (39.1%) Experienced precipitated withdrawal Yes 26 (89.6%) 7 (44%) No 3 (10.3%) 9 (56%) Withdrawal symptoms described as severe Anxiety 25 (83.3%) 8 (50%) Bone/joint pain 22 (73.3%) 5 (31.3%) Insomnia 21 (70%) 6 (37.5%) Sweating 21 (70%) 5 (31.3%) Mood change 18 (60%) 5 (31.3%) Runny nose 19 (63.3%) 4 (25%) Nausea 19 (63.3%) 3 (18.8%) Shakes/tremors 16 (53.3%) 3 (18.8%) Vomiting 16 (53.3%) 1 (6.3%) Loss of appetite 12 (40%) 5 (31.3%) Diarrhea 14 (46.7%) 1 (6.3%) Heard of LDI/ “microdosing” before Heard of LDI/"microdosing" before 13 (43.3%) 13 (43.3%) Source of information (n = 13) Friend 7 (23.3%) Doctor/clinic 5 (16.7%) Internet 1 (3.3%) Tried LDI before 6 (20%) Agreement with the following statements : Agreement with the following statements : Baseline Survey Baseline Survey Confident in ability to get onto buprenorphine using LDI 28 (93.3%) Confident in ability to stay on buprenorphine after LDI 28 (93.3%) Heard that microdosing eliminates precipitated withdrawal 13 (43.3%) Knows someone who has used LDI to get onto buprenorphine bupbuprenorphine 10 (33.3%) Is skeptical about LDI 10 (33.3%) Knows people who have tried LDI 12 (40%) Wanted to try LDI but didn’t know how 9 (30%) Knows someone who tried LDI but was unsuccessful 4 (13.3%) Follow-up survey The LDI method worked for me 11 (68.8%) I reached my goal dose of buprenorphine 6 (37.5%) Median days to initiation (Q1–Q4) 4 (4–6.25) Instructions were easy to follow 13 (81.3%) Fewer withdrawal symptoms than past attempts 11 (68.8%) Would use LDI again 12 (75%) Would recommend LDI to a friend 12 (75%) Felt motivated to continue buprenorphine 13 (81.3%) Followed LDI instructions 10 (62.5%) LDI was more comfortable than past attempts 14 (87.5%) *One participant did not respond to this question in the baseline survey Quantitative Outcomes Sixteen (52%) participants completed a follow-up assessment after a median of 17.5 days from baseline. Of the 16 who completed follow-up, nine (56%) tested positive for buprenorphine (30% of the total cohort) and 11 (69%) endorsed that they found the protocol to be effective; however, only 6 (38%) of participants attested to reaching their goal dose of buprenorphine (Table 3 ). The most reported severe withdrawal symptom was anxiety (50%), followed by insomnia (38%). Most (75%) of participants stated they would use LDI again as a future buprenorphine initiation strategy. Table 3 Qualitative Themes According to COM-B Analysis COM-B Domain Theme Physical capability LDI attenuates physical and psychological opioid withdrawal symptoms Psychological capability LDI instructions were generally helpful, informative, and simple; however, some participants requested additions Automatic motivation Fear and anxiety surrounding BPOW motivates an LDI attempt Reflective motivation Outpatient LDI empowers individuals to engage in deliberate decision-making and set their own recovery goals Physical opportunity Lack of stable environment and structured support undermines successful LDI in street-based contexts. Social opportunity LDI allows individuals to maintain a regular schedule and social role compared to standard induction protocols. Note: COM-B, capability, opportunity, motivation and behavior; BPOW, buprenorphine precipitated withdrawal; LDI, low-dose induction Qualitative Themes Physical Capability : Theme 1: LDI attenuates physical and psychological opioid withdrawal symptoms. When compared to past attempts at buprenorphine induction, participants described a faster, easier, and “definitely more comfortable” experience starting buprenorphine with LDI. In traditional inductions, participants described an “excruciating” first “48 to 72 hours of cold turkey” in which they were “full-blown sick, throwing up and all that.” Another participant stated of traditional induction, “ I had lost a lot of weight and couldn’t eat for a week.” Comparatively, with LDI, most participants reported mild, if any, withdrawal symptoms, as supported by one participant who mentioned he “wasn’t getting any withdrawal symptoms .” Psychological Capability : Theme 2: LDI instructions were generally helpful, informative, and simple; however, some participants requested additions. Beyond being helpful, some participants described the instructions as essential, noting “ without the paper, I probably would’ve been a little lost.” Participants noted that the instructions were not enough to understand LDI alone and state that verbal explanations were essential. One participant stated, “ since you guys thoroughly explained everything to me, I was able to do this.” Some participants requested additions to the instructions, such explicit counseling on concurrent drug use. For example, one participant recommended including instructions to “cut the fentanyl less and less” as the days progress; another requested instruction on “when to take the buprenorphine and when to take the opiate. ” Theme 3: Fear and anxiety surrounding BPOW motivates an LDI attempt. Even participants who never experienced precipitated withdrawal in their lifetime described fear and anxiety surrounding the phenomenon; one stated “I’ve been through the withdrawals so many times now that I know [they] are really scary and will really, really hurt you.” Another participant stated: “ Just the fact that it’s microdosing, and you can do both at the same time, it takes away the fear of that withdrawal effect, because the precipitated withdrawals are horrible. Which, I can’t even really say that I’ve ever actually experienced it, but [it’s] the fear that they put in you” Theme 4: Outpatient LDI empowers individuals to engage in deliberate decision-making and set their own recovery goals. Many participants felt ready to quit fentanyl, but not other substances, and appreciated the flexibility of outpatient LDI versus an inpatient medically supervised detox program. One participant stated, “I can worry about quitting pot another time [because] it’s not heroin and it’s not fentanyl.” Despite verbal counseling to adhere to the dosing regimen on the LDI handout, participants appreciated their autonomy in the ability to tailor buprenorphine dosing to their withdrawal symptoms. Notably, participants took pride in the ability to plan their dosing regimen; one described LDI as “ more empowering ” than past induction experiences while another concluded his interview with the proud statement “ I just did it—like Sinatra said, "I did it my way. " Theme 5: Environmental instability and structured support undermined MOUD induction, including LDI, for people experiencing homelessness. Participants experiencing homelessness noted the difficulty of adhering to the LDI protocol, stating “you’re not getting high from [buprenorphine] and you just wanna block out the pain and the anxiety and the stress from being on the streets.” One reflected on how difficult it was to start buprenorphine surrounded by other people who were “shooting up ” on the streets, stating that “a big thing is just the places and the people.” In addition, participants occasionally accessed street drugs or other substances to alleviate withdrawal symptoms. One participant stated that cannabis “ really help[ed] the cravings ” for fentanyl. Others reported using street fentanyl to manage pain. Another returned to alcohol use after a year of abstinence to manage pain during the withdrawal period. While these lived experiences do not specifically speak to the difficulties of LDI for all people experiencing homelessness, they speak to the difficulty of MOUD induction when self-treating mental and physical pain in a challenging context. Theme 6: LDI allows individuals to maintain a regular schedule and social role compared to standard induction protocols. Avoiding withdrawal by continuing full agonist opioid use during the LDI appeared to decrease interruptions in daily life for people who experience florid withdrawal prior to initiating buprenorphine. As one participant stated that he was “ able to concentrate ” throughout the LDI protocol, which enabled him to “ actually provide… help for those who [were] depending on [him] .” The ability to go to work allowed some participants to receive social support through the workplace during LDI; one participant stated that his boss encouraged him: “you’re fighting the good fight, man. I see your arm’s looking better. You’re healin’ up.” Discussion This pilot study examined the implementation of a 4-day LDI protocol at a low barrier, SSP-based buprenorphine program for people who inject drugs (PWID) in the fentanyl era. While acceptability and feasibility of the LDI protocol were high, nearly half of all participants were lost to follow up and only one-third of participants had objective evidence of recent buprenorphine use on UDS. These data reflect challenges in managing MOUD among PWID with high rates of homelessness and co-occurring stimulant and xylazine use. While prior studies of LDI in the inpatient setting and case series in the outpatient setting have demonstrated high success rates, 8 , 10 our data highlight significant barriers to success of LDI in real-world harm reduction settings. There was a discrepancy between subjective and objective success with the LDI protocol. When looking at our primary outcome of buprenorphine on follow-up UDS, one may interpret LDI at this low-barrier buprenorphine program with mixed success—although fentanyl can remain positive for > 28 days after last use, more participants (81%) tested positive for fentanyl at follow-up than buprenorphine (53%) (Table 1 ). The first study of outpatient LDI attempt similarly found low initiation (34%) and retention (21%) rates. 10 Even with induction options, extensive counseling, and take-home supportive medications for withdrawal symptoms (Fig. 2 ), most participants did not stop using fentanyl. However, in fealty to harm reduction principles, any positive change (e.g., presence of buprenorphine or reduced use) should be viewed as a success and celebrated. One difference between this study and that of Suen et al . is the definitions of successful buprenorphine initiation; Suen defined success as “self-reported LDI completion.” 10 Our study adds objective findings of buprenorphine in UDS and adds rich qualitative evidence to explore the personal motivations, social determinants, and support networks that determine successful buprenorphine induction in a harm reduction setting. In our self-reported measures of LDI success, we found that over two-thirds of participants agreed that LDI worked for them and would use the method again. Somatic and psychological withdrawal symptoms were numerically lower with LDI compared to previous attempts (Tables 2 and 3 ); however, severe psychiatric withdrawal symptoms, including insomnia and anxiety, were still experienced by over half of participants. Understanding the nuances between objective and subjective study outcomes will warrant further qualitative studies to understand barriers to LDI in a harm reduction setting, especially for people with low resources. Qualitative themes further supported higher rates of self-reported successful buprenorphine initiation in our cohort. Participants were motivated to try LDI because they were fearful of the suffering from withdrawal required by traditional induction methods, and overall they found the experience to be more tolerable compared to past experiences. Differences in success rates could be further attributed to a diversity of LDI protocols used in different settings. In considering the gap in effectiveness between inpatient LDI and outpatient LDI, we suspect social determinants of health as the primary drivers of unsuccessful treatment. On a national level, policies preventing prescription of full opioid agonists (e.g., methadone) in the outpatient setting for OUD caused participants to rely on an unstable and unregulated drug supply during LDI. Housing instability and local rehab policies which prohibited buprenorphine, 19 undermined participants’ ability to safely store or access their medication. Lacking proper shelter, nutrition, and support is undoubtedly a barrier to long-term adherence to buprenorphine treatment. The results of this study must be interpreted in the context of several limitations. The high loss to follow up biased the results toward individuals who successfully completed LDI. While we interpreted the primary outcome conservatively, where loss to follow up was considered as being negative for buprenorphine, the qualitative results might not be representative of the cohort overall. Recall bias and social desirability bias could have influenced validity of qualitative findings. Beyond attrition and recall bias, this study is limited by failure to include individuals living with HIV and lack of diversity with respect to participant race and ethnicity; the majority were non-Hispanic White. This study is further limited by a small sample size and lack of a contemporary control group to evaluate how the LDI protocol compares directly to a traditional induction strategy, although data from our SSP indicate a 59% 3-month retention rate on buprenorphine. 14 Conclusion This study addresses a critical gap in qualitative evidence of LDI implementation within harm reduction settings. LDI provides an alternative, humane pathway to starting buprenorphine which participants not only accept but find empowering. Fear of precipitated withdrawal motivated participants to attempt LDI, and they reflected positively on their autonomy in creating their own dosing and recovery goals while maintaining social responsibilities. This mixed-methods study demonstrates higher self-reported success with LDI compared to prior studies in non-harm reduction settings, underscoring the need for additional implementation research to optimize delivery of LDI in this low barrier context. Abbreviations OUD (opioid use disorder), MOUD (medications for opioid use disorder), BPOW (buprenorphine precipitated opioid withdrawal), LDI (low-dose induction), PWID (people who inject drugs), SSP (syringe services program), UDS (urine drug screen), COM-B (capability, opportunity, motivation, and behavior). Declarations Ethics approval and consent to participate: The Institutional Review Board at the University of Miami approved this study (20230483) and written informed consent was obtained from participants. Consent for publication: Written informed consent was obtained from each participant. Availability of data and materials: The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: This study was unfunded. Authors' contributions: MHH under guidance of DPS conceptualized the study, analyzed participant data, and wrote manuscript. PVW, RH, MB, MHH collected participant data. PVW and WHE contributed substantially to qualitative analysis. DWF, TSB, ES, TAC, KJC, HET informed study methodology and oversaw research visits. All authors read and approved the final manuscript. Acknowledgements: Bharat Malhotra References Reuter P, Pardo B, Taylor J. Imagining a fentanyl future: Some consequences of synthetic opioids replacing heroin. Int J Drug Policy Aug. 2021;94:103086. 10.1016/j.drugpo.2020.103086 . CDC, National Center for Health Statistics: U.S. Overdose Deaths Decrease Almost 27% in 2025. https://www.cdc.gov/ (2025). 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Am J Addict Jul. 2021;30(4):305–15. 10.1111/ajad.13135 . Button D, Hartley J, Robbins J, Levander XA, Smith NJ, Englander H. Low-dose Buprenorphine Initiation in Hospitalized Adults With Opioid Use Disorder: A Retrospective Cohort Analysis. J Addict Med Mar-Apr. 2022;01(2):e105–11. 10.1097/ADM.0000000000000864 . Brar R, Fairbairn N, Sutherland C, Nolan S. Use of a novel prescribing approach for the treatment of opioid use disorder: Buprenorphine/naloxone micro-dosing - a case series. Drug Alcohol Rev Jul. 2020;39(5):588–94. 10.1111/dar.13113 . Suen LW, Chiang AY, Jones BLH, et al. Outpatient Low-Dose Initiation of Buprenorphine for People Using Fentanyl. JAMA Netw Open Jan. 2025;2(1):e2456253. 10.1001/jamanetworkopen.2024.56253 . Sokolski E, Skogrand E, Goff A, Englander H. Rapid Low-dose Buprenorphine Initiation for Hospitalized Patients With Opioid Use Disorder. J Addict Med Jul-Aug. 2023;01(4):e278–80. 10.1097/ADM.0000000000001133 . 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Rapid Overlap Initiation Protocol Using Low Dose Buprenorphine for Opioid Use Disorder Treatment in an Outpatient Setting: A Case Series. J Addict Med Sep-Oct. 2022;01(5):534–40. 10.1097/ADM.0000000000000961 . Noel M, Abbs E, Suen L, et al. The Howard Street Method: A Community Pharmacy-led Low Dose Overlap Buprenorphine Initiation Protocol for Individuals Using Fentanyl. J Addict Med Jul-Aug. 2023;01(4):e255–61. 10.1097/ADM.0000000000001154 . Michie S, van Stralen MM, West R. The behaviour change wheel: a new method for characterising and designing behaviour change interventions. Implement Sci Apr. 2011;23:6:42. 10.1186/1748-5908-6-42 . Guido MR, Hauschild MH, Tookes HE, Bartholomew TS, Suarez E. Jr. Limited acceptance of buprenorphine in recovery residences in South Florida: A secret shopper survey. J Subst Use Addict Treat Jan. 2025;168:209535. 10.1016/j.josat.2024.209535 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 06 Apr, 2026 Read the published version in Addiction Science & Clinical Practice → Version 1 posted Editorial decision: Revision requested 16 Dec, 2025 Reviews received at journal 02 Dec, 2025 Reviewers agreed at journal 04 Nov, 2025 Reviews received at journal 27 Aug, 2025 Reviewers agreed at journal 11 Aug, 2025 Reviewers agreed at journal 05 Aug, 2025 Reviewers invited by journal 05 Aug, 2025 Editor assigned by journal 05 Aug, 2025 Submission checks completed at journal 25 Jul, 2025 First submitted to journal 18 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7160434","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":496216192,"identity":"38b037df-f8ad-48cf-bf73-9d73ceb70d96","order_by":0,"name":"Maia H. Hauschild","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYFACxgZmEMUPIhIKSNEi2QDSYkCkPWAtBgfAJBHKddsPN34uqDlsb3x+deKHBwYM8vxiB/BrMTuT2Cw949jhxG033m6WADrMcObsBAJaDiQ2SPOwHU4wu3F2A0hLgsFtQlrOP2z+zfMP6LAZZzf/IE7LjcQ2ad62w4wb+Hu3EWnLjYdt1rx96YkzbvBus0gwkCDCL+fTH9/m+WZtz99/dvPNHxU28vzSBLQggARYpQSxykGA/wApqkfBKBgFo2AkAQAxeEeIiid1FAAAAABJRU5ErkJggg==","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Maia","middleName":"H.","lastName":"Hauschild","suffix":""},{"id":496216193,"identity":"29a739e5-8f22-4808-889f-07a5e42ebd70","order_by":1,"name":"Peyton V Warp","email":"","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Peyton","middleName":"V","lastName":"Warp","suffix":""},{"id":496216194,"identity":"c401e43b-b028-4afc-b03f-fbf371a67ac3","order_by":2,"name":"William H Eger","email":"","orcid":"","institution":"University of California San Diego","correspondingAuthor":false,"prefix":"","firstName":"William","middleName":"H","lastName":"Eger","suffix":""},{"id":496216195,"identity":"682caee3-7e82-425a-a229-6bf763fceea0","order_by":3,"name":"Ryan Hood","email":"","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ryan","middleName":"","lastName":"Hood","suffix":""},{"id":496216196,"identity":"36b3b90a-a592-450a-952a-fce835f0bb3a","order_by":4,"name":"Monica Bahamon","email":"","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Monica","middleName":"","lastName":"Bahamon","suffix":""},{"id":496216197,"identity":"0413b255-cac0-4273-84f8-fe90655e43b7","order_by":5,"name":"David W. Forrest","email":"","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"W.","lastName":"Forrest","suffix":""},{"id":496216198,"identity":"0f4ca0fb-0210-4989-86f5-be9d4162ce5a","order_by":6,"name":"Tyler S. Bartholomew","email":"","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Tyler","middleName":"S.","lastName":"Bartholomew","suffix":""},{"id":496216199,"identity":"c3750bcc-015c-4822-9d50-42c58554cbeb","order_by":7,"name":"Edward Suarez","email":"","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Edward","middleName":"","lastName":"Suarez","suffix":""},{"id":496216200,"identity":"b74335d1-1089-4693-8dba-b660a6ce765f","order_by":8,"name":"Teresa A. Chueng","email":"","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Teresa","middleName":"A.","lastName":"Chueng","suffix":""},{"id":496216201,"identity":"338a6bbb-0d16-43b1-a2f6-98fdbde7a2da","order_by":9,"name":"Katrina J. Ciraldo","email":"","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Katrina","middleName":"J.","lastName":"Ciraldo","suffix":""},{"id":496216202,"identity":"b7be6a54-e099-481a-a189-205b7a6d6861","order_by":10,"name":"Hansel E. Tookes","email":"","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hansel","middleName":"E.","lastName":"Tookes","suffix":""},{"id":496216203,"identity":"34e054ac-5048-4490-8f0a-40321fc0f6c3","order_by":11,"name":"David P Serota","email":"","orcid":"","institution":"University of Miami Miller School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"P","lastName":"Serota","suffix":""}],"badges":[],"createdAt":"2025-07-18 20:08:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7160434/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7160434/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13722-026-00661-7","type":"published","date":"2026-04-06T15:58:46+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88782557,"identity":"43fceca7-138e-41c4-93cf-b4e02d480f5c","added_by":"auto","created_at":"2025-08-11 11:05:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":309405,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLDI Handout\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAdapted from David Tian MD.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7160434/v1/d8d6cde7a10944a4b2303d37.png"},{"id":88782081,"identity":"c169ec36-523f-4d3e-a14c-7fd74a2490c3","added_by":"auto","created_at":"2025-08-11 10:57:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":55559,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePhysician Orders\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7160434/v1/77ee960112e10de0b53f8117.png"},{"id":106810400,"identity":"beba86ef-9a3c-4083-ac11-a2f2c79c401c","added_by":"auto","created_at":"2026-04-13 16:15:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1734849,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7160434/v1/e180740d-644b-499c-9164-ed33186f5b69.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Implementation of Low-Dose Buprenorphine Induction at a Syringe Services Program: A Pilot Study","fulltext":[{"header":"Background","content":"\u003cp\u003eIllicitly manufactured fentanyl exacerbated the national overdose crisis when it replaced heroin as the dominant opioid in several major illicit drug markets in North America in the second decade of the 21st century.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e While national drug overdose rates began to decline in 2023 for the first time since 2018, there were still greater than 48,000 overdose deaths related to fentanyl in 2024.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Safe and effective medications for opioid use disorder (MOUD), including the partial opioid agonist buprenorphine, have resulted in reductions in overdose and serious opioid-related acute care use.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Beyond systemic barriers to treatment, people with opioid use disorder (OUD) face the risk of buprenorphine-precipitated opioid withdrawal (BPOW). BPOW is a phenomenon in which opioid withdrawal symptoms are paradoxically worsened by the initiation of buprenorphine due to its activity as a high-affinity partial-agonist at the mu-opioid receptor. The lipophilicity of fentanyl, which prolongs tissue retention, increases the intensity of BPOW and necessitates the urgent need for new ways to initiate buprenorphine in the fentanyl era. Multilevel challenges to starting buprenorphine contribute to low treatment initiation and retention as well as high mortality among people with OUD, especially in the context of high fentanyl adulteration in unregulated opioid supplies.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe American Society of Addiction Medicine’s clinical practice guidelines favor waiting until patients experience objective signs of opioid withdrawal before taking the first dose of buprenorphine to avoid BPOW.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Under this model, nausea, vomiting, diarrhea, anxiety and pain are expected. Despite these recommendations, up to 45% of patients who initiate buprenorphine after fentanyl use report severe worsening of withdrawal symptoms with buprenorphine.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e An alternative approach, often referred to as microdose-induction or low-dose induction (LDI), has emerged to remove the withdrawal prerequisite for buprenorphine initiation. LDI involves administering small escalating doses of buprenorphine prior to development of severe withdrawal symptoms to minimize the risk of BPOW.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e The efficacy of LDI, particularly for individuals averse to withdrawal or using fentanyl, has been demonstrated in inpatient settings with close clinical supervision.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWhile case reports have suggested the feasibility and success of LDI in outpatient substance use disorder clinics,\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e a larger study by \u003cem\u003eSuen et al.\u003c/em\u003e found only 34% of people using an LDI protocol successfully initiated buprenorphine in the outpatient setting.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e While various LDI protocols are well-documented,\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e there remains a critical need to determine best practices for LDI implementation in low-barrier harm reduction settings, like syringe services programs (SSPs), to increase buprenorphine uptake and retention for the most vulnerable patients, including those experiencing homelessness.\u003c/p\u003e\u003cp\u003eTo address this gap, we adapted a 4-day LDI treatment protocol and began offering patients the LDI buprenorphine initiation at an SSP in Miami, Florida.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e In this mixed-methods pilot study, we aimed to evaluate the preliminary clinical outcomes of LDI for initiating buprenorphine while examining implementation outcomes (e.g., feasibility, acceptability) in a real-world harm reduction setting.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eStudy Design and Setting\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe conducted a prospective cohort study from June 2023 to June 2024 of patients with a diagnosis of moderate to severe OUD per the \u003cem\u003eDiagnostic and Statistical Manual of Mental Disorders\u003c/em\u003e (Fifth Edition) seeking buprenorphine from their local SSP (IDEA Miami). The SSP provides harm reduction services, wound care, and substance use disorder treatment services, including buprenorphine for OUD, to individuals regardless of insurance status.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e The Institutional Review Board at the University of Miami approved this study (UM IRB #20230483) and written informed consent was obtained from participants. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines were followed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eRecruitment and Data Collection\u003c/b\u003e\u003c/p\u003e\u003cp\u003eEligible participants were adults aged 18 years or older with moderate to severe OUD who tested negative for buprenorphine by urine drug screen (UDS) while presenting for buprenorphine induction. Individuals interested in participating provided written informed consent and met with a clinician to review their substance use history and goals for treatment. Participants were presented with options for buprenorphine initiation, including LDI and traditional initiation, as well as referral to methadone treatment. For participants who completed the informed consent process, physicians provided counseling on the 4-day LDI protocol and an instructional handout (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Prescriptions for buprenorphine and medications to alleviate any withdrawal symptoms were sent to an affiliated outpatient pharmacy. Results of a 13-panel UDS, in addition to xylazine testing results were also recorded.\u003c/p\u003e\u003cp\u003eBesides the UDS results, all data collected were self-reported; at the conclusion of the initial clinical visit, participants completed an interviewer-administered baseline survey assessing demographic characteristics and prior experiences with buprenorphine. In the survey, participants rated withdrawal symptoms associated with past buprenorphine induction experiences on a scale of mild to severe. Participants were compensated \u003cspan\u003e$\u003c/span\u003e10 for completion of the initial study visit. Participants were asked to return to the clinic within four weeks for follow-up procedures.\u003c/p\u003e\u003cp\u003eAt the follow-up visit, a UDS, a survey about participants’ withdrawal symptoms and semi-structured qualitative interviews were completed for each participant. All interviews took place in person in a confidential space and were conducted by trained student researchers. Interviews were audio-recorded, professionally transcribed and reviewed by the research team for accuracy. Participants received an additional \u003cspan\u003e$\u003c/span\u003e10 for completing all follow-up procedures.\u003c/p\u003e\u003cp\u003e\u003cb\u003eOutcomes of Interest\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe primary outcome was successful buprenorphine initiation, defined as having a UDS positive for buprenorphine at the follow-up visit. Treatment success is presented for those who attended a follow-up visit as well as for the whole cohort, where loss to follow-up was considered unsuccessful treatment.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Analyses\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDescriptive statistics are presented as percentages for categorical variables and medians and interquartile ranges for continuous variables. Analyses were completed using Microsoft Excel (Version 16.96).\u003c/p\u003e\u003cp\u003eOur qualitative analysis process for follow-up interviews followed an “open-coding” process informed by the Capability, Opportunity, Motivation, and Behavior (COM-B) framework. Structuring thematic analysis around the COM-B components allowed researchers to systematically identify barriers and facilitators to behavior change as reported by participants, allowing inductive themes to emerge from the data. COM-B was chosen for its structured approach to developing targeted interventions, which involves evaluating individuals’ capability, motivation, and opportunity to engage in a specific behavior, while accounting for the broader contextual factors that influence change.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Three graduate-level qualitative analysts (MHH, PVW, WHE) first read small batches of transcripts to gain a broad understanding of topics covered and to develop a series of memos to clarify emergent ideas and dominant COM-B constructs. Qualitative memos were developed for approximately one-third of transcripts to ensure no additional inductive ideas were present and to develop a preliminary codebook. After development of the preliminary codebook, which included specific inclusion and exclusion criteria, two team members met biweekly to address discrepancies in their independent coding process and to further refine the codebook until coding consensus —defined as consistent application of the codes to transcripts—was established. Coding consensus was achieved after approximately 20% of transcripts were double-coded and reviewed through consensus discussions. A third analyst was consulted in the rare instances where consensus could not be reached between the initial coders. Once all transcript data was coded, the coded passages were read by all three qualitative analysts to identify themes. The team refined the final themes through discussions with the rest of the research team, which are presented below. All coding was completed using NVivo 14 (QSR International Pty Ltd, 2020).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eBaseline Characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFrom June 2023 to June 2024, 45 participants presenting to the SSP to start buprenorphine were approached for enrollment in the study. Thirty participants seeking LDI buprenorphine initiation were enrolled (median age\u0026thinsp;=\u0026thinsp;35, 53% male). Nearly half of participants self-reported being unhoused (47%) and a hepatitis C diagnosis (47%), and 37% reported a post-traumatic stress disorder diagnosis (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). UDS results at baseline were 97% positive for fentanyl, 76% for cocaine, and 64% for xylazine.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eParticipant Demographics and Health Characteristics at Baseline and Follow-Up\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFollow-Up (N\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge (median, Q1\u0026ndash;Q4)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (32\u0026ndash;40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35 (30.5\u0026ndash;39)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (53.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (68.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWoman\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (46.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (31.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRace/Ethnicity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite non-Hispanic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (53%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (50%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite Hispanic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (43.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlack Hispanic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNative American\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHousing Status\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eApartment/House\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (53.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (50%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnhoused\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (46.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (50%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStreet/camping/squatting\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (64.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (31.3%)\u003c/p\u003e\u003cp\u003e3 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCouch surfing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (35.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEducational Attainment\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGraduated high school\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (80%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (75%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDid not graduate high school\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSmokes Tobacco\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25 (83.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (81.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEmployment Status*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnemployed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (66.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (68.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEmployed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (23.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnable to work\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLifetime Diagnoses (self-report)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHepatitis C\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (46.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (50%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePTSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (36.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (31.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneralized anxiety disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMajor depressive disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eADHD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAsthma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBipolar disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (12.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic wounds/ulcers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUDS Results at Baseline\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFentanyl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (96.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (81.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCocaine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (73.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (75%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBuprenorphine\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0 (0%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e9 (56%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eXylazine**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (64.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMDMA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (36.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (43.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCannabis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (43.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBenzodiazepines\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (37.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAmphetamine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (12.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOpiates\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (43.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEthyl glucuronide\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (12.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMethamphetamines\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (12.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMethadone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOxycodone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBarbiturates\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e*One participant did not respond to this question in the baseline survey\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e**28 participants were tested for xylazine.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMost participants (80%) reported previous buprenorphine treatment experience and fewer than 5 lifetime induction attempts (79%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Ninety percent (90%) reported ever experiencing BPOW in the past. The most reported severe symptoms of opioid withdrawal were anxiety (83%), bone/joint pain (73%), sweating (70%) and insomnia (70%). Over half reported experiencing severe nausea (63%), runny nose (63%), mood change (60%), vomiting (53%), and shakes/tremor (53%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Before study enrollment, fewer than half (43%) of participants were familiar with LDI and 20% had previously attempted to use an LDI method (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eExperiences with Buprenorphine\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAt Baseline (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAfter LDI (N\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious buprenorphine induction attempts\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;5 attempts\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (79.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;5 attempts\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (20.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePrevious buprenorphine treatment duration\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (80%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026le; 1 year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (60.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;1 year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (39.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExperienced precipitated withdrawal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (89.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (44%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (10.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (56%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWithdrawal symptoms described as severe\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25 (83.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBone/joint pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (73.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (31.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInsomnia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (37.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSweating\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (70%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (31.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMood change\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (60%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (31.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRunny nose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (63.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNausea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (63.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eShakes/tremors\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (53.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVomiting\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (53.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLoss of appetite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (31.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiarrhea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (46.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHeard of LDI/ \u0026ldquo;microdosing\u0026rdquo; before\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eHeard of LDI/\"microdosing\" before\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (43.3%)\u003c/p\u003e\u003cp\u003e13 (43.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSource of information (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFriend\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (23.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDoctor/clinic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInternet\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTried LDI before\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (20%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAgreement with the following statements\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003eAgreement with the following statements\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003eBaseline Survey\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline Survey\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConfident in ability to get onto buprenorphine using LDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (93.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConfident in ability to stay on buprenorphine after LDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (93.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeard that microdosing eliminates precipitated withdrawal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (43.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKnows someone who has used LDI to get onto buprenorphine bupbuprenorphine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIs skeptical about LDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKnows people who have tried LDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (40%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWanted to try LDI but didn\u0026rsquo;t know how\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (30%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKnows someone who tried LDI but was unsuccessful\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFollow-up survey\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThe LDI method worked for me\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (68.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eI reached my goal dose of buprenorphine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (37.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian days to initiation (Q1\u0026ndash;Q4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (4\u0026ndash;6.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInstructions were easy to follow\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (81.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFewer withdrawal symptoms than past attempts\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (68.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWould use LDI again\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWould recommend LDI to a friend\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFelt motivated to continue buprenorphine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (81.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFollowed LDI instructions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (62.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDI was more comfortable than past attempts\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (87.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e*One participant did not respond to this question in the baseline survey\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eQuantitative Outcomes\u003c/b\u003e\u003c/p\u003e\u003cp\u003eSixteen (52%) participants completed a follow-up assessment after a median of 17.5 days from baseline. Of the 16 who completed follow-up, nine (56%) tested positive for buprenorphine (30% of the total cohort) and 11 (69%) endorsed that they found the protocol to be effective; however, only 6 (38%) of participants attested to reaching their goal dose of buprenorphine (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The most reported severe withdrawal symptom was anxiety (50%), followed by insomnia (38%). Most (75%) of participants stated they would use LDI again as a future buprenorphine initiation strategy.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eQualitative Themes According to COM-B Analysis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOM-B Domain\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTheme\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhysical capability\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLDI attenuates physical and psychological opioid withdrawal symptoms\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePsychological capability\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLDI instructions were generally helpful, informative, and simple; however, some participants requested additions\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutomatic motivation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFear and anxiety surrounding BPOW motivates an LDI attempt\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReflective motivation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOutpatient LDI empowers individuals to engage in deliberate decision-making and set their own recovery goals\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhysical opportunity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLack of stable environment and structured support undermines successful LDI in street-based contexts.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSocial opportunity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLDI allows individuals to maintain a regular schedule and social role compared to standard induction protocols.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eNote: COM-B, capability, opportunity, motivation and behavior; BPOW, buprenorphine precipitated withdrawal; LDI, low-dose induction\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eQualitative Themes\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePhysical Capability\u003c/span\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003eTheme 1: LDI attenuates physical and psychological opioid withdrawal symptoms.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWhen compared to past attempts at buprenorphine induction, participants described a faster, easier, and \u003cem\u003e\u0026ldquo;definitely more comfortable\u0026rdquo;\u003c/em\u003e experience starting buprenorphine with LDI. In traditional inductions, participants described an \u003cem\u003e\u0026ldquo;excruciating\u0026rdquo;\u003c/em\u003e first \u003cem\u003e\u0026ldquo;48 to 72 hours of cold turkey\u0026rdquo;\u003c/em\u003e in which they were \u003cem\u003e\u0026ldquo;full-blown sick, throwing up and all that.\u0026rdquo;\u003c/em\u003e Another participant stated of traditional induction, \u0026ldquo;\u003cem\u003eI had lost a lot of weight and couldn\u0026rsquo;t eat for a week.\u0026rdquo;\u003c/em\u003e Comparatively, with LDI, most participants reported mild, if any, withdrawal symptoms, as supported by one participant who mentioned he \u003cem\u003e\u0026ldquo;wasn\u0026rsquo;t getting any withdrawal symptoms\u003c/em\u003e.\u0026rdquo;\u003c/p\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePsychological Capability\u003c/span\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003eTheme 2: LDI instructions were generally helpful, informative, and simple; however, some participants requested additions.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBeyond being helpful, some participants described the instructions as essential, noting \u0026ldquo;\u003cem\u003ewithout the paper, I probably would\u0026rsquo;ve been a little lost.\u0026rdquo;\u003c/em\u003e Participants noted that the instructions were not enough to understand LDI alone and state that verbal explanations were essential. One participant stated, \u0026ldquo;\u003cem\u003esince you guys thoroughly explained everything to me, I was able to do this.\u0026rdquo;\u003c/em\u003e Some participants requested additions to the instructions, such explicit counseling on concurrent drug use. For example, one participant recommended including instructions to \u003cem\u003e\u0026ldquo;cut the fentanyl less and less\u0026rdquo;\u003c/em\u003e as the days progress; another requested instruction on \u003cem\u003e\u0026ldquo;when to take the buprenorphine and when to take the opiate.\u003c/em\u003e\u0026rdquo;\u003c/p\u003e\u003cp\u003e\u003cb\u003eTheme 3: Fear and anxiety surrounding BPOW motivates an LDI attempt.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eEven participants who never experienced precipitated withdrawal in their lifetime described fear and anxiety surrounding the phenomenon; one stated \u003cem\u003e\u0026ldquo;I\u0026rsquo;ve been through the withdrawals so many times now that I know [they] are really scary and will really, really hurt you.\u0026rdquo;\u003c/em\u003e Another participant stated:\u003c/p\u003e\u003cp\u003e\u0026ldquo;\u003cem\u003eJust the fact that it\u0026rsquo;s microdosing, and you can do both at the same time, it takes away\u003c/em\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003ethe fear of that withdrawal effect, because the precipitated withdrawals are horrible.\u003c/em\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u003cem\u003eWhich, I can\u0026rsquo;t even really say that I\u0026rsquo;ve ever actually experienced it, but [it\u0026rsquo;s] the fear that they put in you\u0026rdquo;\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eTheme 4: Outpatient LDI empowers individuals to engage in deliberate decision-making and set their own recovery goals.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMany participants felt ready to quit fentanyl, but not other substances, and appreciated the flexibility of outpatient LDI versus an inpatient medically supervised detox program. One participant stated, \u003cem\u003e\u0026ldquo;I can worry about quitting pot another time [because] it\u0026rsquo;s not heroin and it\u0026rsquo;s not fentanyl.\u0026rdquo;\u003c/em\u003e Despite verbal counseling to adhere to the dosing regimen on the LDI handout, participants appreciated their autonomy in the ability to tailor buprenorphine dosing to their withdrawal symptoms. Notably, participants took pride in the ability to plan their dosing regimen; one described LDI as \u0026ldquo;\u003cem\u003emore empowering\u003c/em\u003e\u0026rdquo; than past induction experiences while another concluded his interview with the proud statement \u0026ldquo;\u003cem\u003eI just did it\u0026mdash;like Sinatra said, \"I did it my way.\u003c/em\u003e\"\u003c/p\u003e\u003cp\u003e\u003cb\u003eTheme 5: Environmental instability and structured support undermined MOUD induction, including LDI, for people experiencing homelessness.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eParticipants experiencing homelessness noted the difficulty of adhering to the LDI protocol, stating \u003cem\u003e\u0026ldquo;you\u0026rsquo;re not getting high from [buprenorphine] and you just wanna block out the pain and the anxiety and the stress from being on the streets.\u0026rdquo;\u003c/em\u003e One reflected on how difficult it was to start buprenorphine surrounded by other people who were \u003cem\u003e\u0026ldquo;shooting up\u003c/em\u003e\u0026rdquo; on the streets, stating that \u003cem\u003e\u0026ldquo;a big thing is just the places and the people.\u0026rdquo;\u003c/em\u003e In addition, participants occasionally accessed street drugs or other substances to alleviate withdrawal symptoms. One participant stated that cannabis \u0026ldquo;\u003cem\u003ereally help[ed] the cravings\u003c/em\u003e\u0026rdquo; for fentanyl. Others reported using street fentanyl to manage pain. Another returned to alcohol use after a year of abstinence to manage pain during the withdrawal period. While these lived experiences do not specifically speak to the difficulties of LDI for all people experiencing homelessness, they speak to the difficulty of MOUD induction when self-treating mental and physical pain in a challenging context.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTheme 6: LDI allows individuals to maintain a regular schedule and social role compared to standard induction protocols.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAvoiding withdrawal by continuing full agonist opioid use during the LDI appeared to decrease interruptions in daily life for people who experience florid withdrawal prior to initiating buprenorphine. As one participant stated that he was \u0026ldquo;\u003cem\u003eable to concentrate\u003c/em\u003e\u0026rdquo; throughout the LDI protocol, which enabled him to \u0026ldquo;\u003cem\u003eactually provide\u0026hellip; help for those who [were] depending on [him]\u003c/em\u003e.\u0026rdquo; The ability to go to work allowed some participants to receive social support through the workplace during LDI; one participant stated that his boss encouraged him: \u003cem\u003e\u0026ldquo;you\u0026rsquo;re fighting the good fight, man. I see your arm\u0026rsquo;s looking better. You\u0026rsquo;re healin\u0026rsquo; up.\u0026rdquo;\u003c/em\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis pilot study examined the implementation of a 4-day LDI protocol at a low barrier, SSP-based buprenorphine program for people who inject drugs (PWID) in the fentanyl era. While acceptability and feasibility of the LDI protocol were high, nearly half of all participants were lost to follow up and only one-third of participants had objective evidence of recent buprenorphine use on UDS. These data reflect challenges in managing MOUD among PWID with high rates of homelessness and co-occurring stimulant and xylazine use. While prior studies of LDI in the inpatient setting and case series in the outpatient setting have demonstrated high success rates, \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e our data highlight significant barriers to success of LDI in real-world harm reduction settings.\u003c/p\u003e\u003cp\u003eThere was a discrepancy between subjective and objective success with the LDI protocol. When looking at our primary outcome of buprenorphine on follow-up UDS, one may interpret LDI at this low-barrier buprenorphine program with mixed success\u0026mdash;although fentanyl can remain positive for \u0026gt;\u0026thinsp;28 days after last use, more participants (81%) tested positive for fentanyl at follow-up than buprenorphine (53%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The first study of outpatient LDI attempt similarly found low initiation (34%) and retention (21%) rates.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Even with induction options, extensive counseling, and take-home supportive medications for withdrawal symptoms (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), most participants did not stop using fentanyl. However, in fealty to harm reduction principles, any positive change (e.g., presence of buprenorphine or reduced use) should be viewed as a success and celebrated.\u003c/p\u003e\u003cp\u003eOne difference between this study and that of \u003cem\u003eSuen et al\u003c/em\u003e. is the definitions of successful buprenorphine initiation; Suen defined success as \u0026ldquo;self-reported LDI completion.\u0026rdquo;\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Our study adds objective findings of buprenorphine in UDS and adds rich qualitative evidence to explore the personal motivations, social determinants, and support networks that determine successful buprenorphine induction in a harm reduction setting. In our self-reported measures of LDI success, we found that over two-thirds of participants agreed that LDI worked for them and would use the method again. Somatic and psychological withdrawal symptoms were numerically lower with LDI compared to previous attempts (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e); however, severe psychiatric withdrawal symptoms, including insomnia and anxiety, were still experienced by over half of participants. Understanding the nuances between objective and subjective study outcomes will warrant further qualitative studies to understand barriers to LDI in a harm reduction setting, especially for people with low resources.\u003c/p\u003e\u003cp\u003eQualitative themes further supported higher rates of self-reported successful buprenorphine initiation in our cohort. Participants were motivated to try LDI because they were fearful of the suffering from withdrawal required by traditional induction methods, and overall they found the experience to be more tolerable compared to past experiences. Differences in success rates could be further attributed to a diversity of LDI protocols used in different settings.\u003c/p\u003e\u003cp\u003eIn considering the gap in effectiveness between inpatient LDI and outpatient LDI, we suspect social determinants of health as the primary drivers of unsuccessful treatment. On a national level, policies preventing prescription of full opioid agonists (e.g., methadone) in the outpatient setting for OUD caused participants to rely on an unstable and unregulated drug supply during LDI. Housing instability and local rehab policies which prohibited buprenorphine,\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e undermined participants\u0026rsquo; ability to safely store or access their medication. Lacking proper shelter, nutrition, and support is undoubtedly a barrier to long-term adherence to buprenorphine treatment.\u003c/p\u003e\u003cp\u003eThe results of this study must be interpreted in the context of several limitations. The high loss to follow up biased the results toward individuals who successfully completed LDI. While we interpreted the primary outcome conservatively, where loss to follow up was considered as being negative for buprenorphine, the qualitative results might not be representative of the cohort overall. Recall bias and social desirability bias could have influenced validity of qualitative findings. Beyond attrition and recall bias, this study is limited by failure to include individuals living with HIV and lack of diversity with respect to participant race and ethnicity; the majority were non-Hispanic White. This study is further limited by a small sample size and lack of a contemporary control group to evaluate how the LDI protocol compares directly to a traditional induction strategy, although data from our SSP indicate a 59% 3-month retention rate on buprenorphine.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study addresses a critical gap in qualitative evidence of LDI implementation within harm reduction settings. LDI provides an alternative, humane pathway to starting buprenorphine which participants not only accept but find empowering. Fear of precipitated withdrawal motivated participants to attempt LDI, and they reflected positively on their autonomy in creating their own dosing and recovery goals while maintaining social responsibilities. This mixed-methods study demonstrates higher self-reported success with LDI compared to prior studies in non-harm reduction settings, underscoring the need for additional implementation research to optimize delivery of LDI in this low barrier context.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eOUD (opioid use disorder), MOUD (medications for opioid use disorder), BPOW (buprenorphine precipitated opioid withdrawal), LDI (low-dose induction), PWID (people who inject drugs), SSP (syringe services program), UDS (urine drug screen), COM-B (capability, opportunity, motivation, and behavior).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate:\u0026nbsp;The Institutional Review Board\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;at the University of Miami approved this study (20230483) and written informed consent was obtained from participants.\u003c/p\u003e\n\u003cp\u003eConsent for publication: Written informed consent was obtained from each participant.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials: The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests: The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding: This study was unfunded.\u003c/p\u003e\n\u003cp\u003eAuthors' contributions: MHH under guidance of DPS conceptualized the study, analyzed participant data, and wrote manuscript. PVW, RH, MB, MHH collected participant data. PVW and WHE contributed substantially to qualitative analysis. DWF, TSB, ES, TAC, KJC, HET informed study methodology and oversaw research visits. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements: Bharat Malhotra\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eReuter P, Pardo B, Taylor J. Imagining a fentanyl future: Some consequences of synthetic opioids replacing heroin. 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J Subst Use Addict Treat Jan. 2025;168:209535. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.josat.2024.209535\u003c/span\u003e\u003cspan address=\"10.1016/j.josat.2024.209535\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"addiction-science-and-clinical-practice","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ascp","sideBox":"Learn more about [Addiction Science \u0026 Clinical Practice](https://ascpjournal.biomedcentral.com/)","snPcode":"13722","submissionUrl":"https://submission.nature.com/new-submission/13722/3","title":"Addiction Science \u0026 Clinical Practice","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"addiction, opioid use disorder, fentanyl, buprenorphine, low-dose induction, microdose","lastPublishedDoi":"10.21203/rs.3.rs-7160434/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7160434/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Fentanyl’s penetration into the unregulated drug supply has complicated the treatment of opioid use disorder (OUD), particularly by increasing the risk of buprenorphine-precipitated opioid withdrawal (BPOW). Buprenorphine, a partial opioid agonist, remains a first-line treatment for OUD, but traditional induction methods can be intolerable for people using fentanyl. Low-dose induction (LDI), a strategy characterized by gradual buprenorphine titration without prior withdrawal, has emerged as a promising alternative to mitigate BPOW. However, the feasibility and acceptability of LDI in low-barrier, real-world settings such as syringe services programs (SSPs) remain underexplored.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We conducted a mixed-methods prospective cohort study from June 2023–2024 at an SSP in Miami, Florida, offering a 4-day LDI protocol to patients with OUD who were interested in starting buprenorphine. Follow-up, conducted on a walk-in basis within four weeks, included urine drug screens (UDS), symptom surveys and semi-structured qualitative interviews. The primary outcome was successful buprenorphine initiation, defined by a positive UDS for buprenorphine at follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Of the 30 participants enrolled in the 4-day LDI protocol, most (n=29) had prior buprenorphine experience and nearly 90% (n=26) reported past BPOW. Only 16 (53%) returned for follow-up. Nine (56%) of those followed up tested positive for buprenorphine, 11 (68.8%) reported that LDI worked for them, and 12 (75%) said they would use the method again. Qualitative interviews revealed six key themes: 1) LDI mitigates withdrawal symptoms; 2) instructions were helpful but could be improved; 3) fear of BPOW motivated LDI use; 4) LDI enabled autonomy in recovery; 5) unstable living environments hindered adherence; and 6) LDI allowed participants to maintain social roles.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e While only 30% of the cohort had objective evidence of buprenorphine induction, most reported successful attempts and found LDI acceptable and empowering. High loss to follow-up and environmental instability limited our conclusions in this outpatient harm reduction setting. These findings underscore the potential of LDI to reduce barriers to buprenorphine use, especially when adapted to real-world constraints. Further research is needed to refine LDI protocols and address the structural determinants affecting treatment success among people who use fentanyl.\u003c/p\u003e","manuscriptTitle":"Implementation of Low-Dose Buprenorphine Induction at a Syringe Services Program: A Pilot Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-11 10:57:49","doi":"10.21203/rs.3.rs-7160434/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-16T17:03:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-03T01:25:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"261659882047099162185571251511392062077","date":"2025-11-04T16:21:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-27T17:41:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"120075317711273865318341413527530589672","date":"2025-08-11T17:51:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"40439933975268405514198390015581141423","date":"2025-08-05T20:58:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-05T20:52:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-05T18:38:07+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-25T18:52:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"Addiction Science \u0026 Clinical Practice","date":"2025-07-18T19:55:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"addiction-science-and-clinical-practice","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ascp","sideBox":"Learn more about [Addiction Science \u0026 Clinical Practice](https://ascpjournal.biomedcentral.com/)","snPcode":"13722","submissionUrl":"https://submission.nature.com/new-submission/13722/3","title":"Addiction Science \u0026 Clinical Practice","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0a4b63b5-cf34-4183-9ab0-647fda03279b","owner":[],"postedDate":"August 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-13T16:11:28+00:00","versionOfRecord":{"articleIdentity":"rs-7160434","link":"https://doi.org/10.1186/s13722-026-00661-7","journal":{"identity":"addiction-science-and-clinical-practice","isVorOnly":false,"title":"Addiction Science \u0026 Clinical Practice"},"publishedOn":"2026-04-06 15:58:46","publishedOnDateReadable":"April 6th, 2026"},"versionCreatedAt":"2025-08-11 10:57:49","video":"","vorDoi":"10.1186/s13722-026-00661-7","vorDoiUrl":"https://doi.org/10.1186/s13722-026-00661-7","workflowStages":[]},"version":"v1","identity":"rs-7160434","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7160434","identity":"rs-7160434","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}