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.”