Guest Editorial – Street Addiction Medicine: Bringing a Patient-Centered Approach for Opioid and Stimulant Use Disorder to the Unhoused

The Crisis on Our Streets

People experiencing homelessness face an extraordinary risk of fatal drug overdose: in Los Angeles County, overdose mortality is 48.8 times higher than the general population, mirroring national trends.^1,2 The majority of these deaths are attributed to methamphetamines and illicit opioids (fentanyl), with overdose outpacing the second cause of death, coronary heart disease, more than 3 to 1.¹ For people experiencing unsheltered homelessness—those living outside of the shelter system, sleeping under bridges, on sidewalks, in riverbeds—the mortality risk is even greater. Simply by living outdoors, people experiencing unsheltered homelessness suffer a mortality rate 3 times that of their sheltered peers and experience a life expectancy 20 years shorter than the national average.^3,4 The cause is multifactorial, as not only do people experiencing unsheltered homelessness report higher rates of chronic medical conditions, mental health diagnoses, and substance use disorders, but they also disproportionately suffer tri-morbidity 48% more than those who are sheltered.⁵

Barriers to Care

Barriers to care for unhoused persons are steep, multifaceted, and both individual and structural. The US health care system places the impetus on the patient to seek medical care when needed. However, this assumption becomes impaired when seeking this care intercepts patients' competing survival needs and fear of mistreatment. Unsheltered patients often prioritize securing food or safety for themselves, their partner, or pet, over workup of acute or chronic health concerns.^6,7 Additionally, this population reports discrimination and mistreatment in health care settings based on housing status, mental health conditions, and/or cognitive issues, which disincentivizes them from seeking care. Those with substance use disorders fear going into withdrawal in waiting rooms, being labeled as "pain seeking" or not having their pain needs met. Once inpatient, perceived loss of autonomy and lack of support or advocacy promotes further mistrust in the medical system.^8,9

The US health care system is not built to serve people experiencing unsheltered homelessness, and as such is fraught with systemic barriers for this population. Maintaining active health insurance when living without an address, phone, or internet is onerous. Appointments often require navigating complicated phone trees and having a working call-back number. Transportation to a clinic (if transportation is available) means leaving their encampment and risking theft of all possessions, and once at the appointment or pharmacy the copay may not be financially feasible. Additionally, the medical system relies on calendared appointments, often exceeding the planning horizon for patients surviving in a day-to-day dynamic street environment.^7,8,9

These barriers compound into late and more severe clinical presentations with subsequent fragmented follow-up, including access to addiction medicine services.

Street (Addiction) Medicine

Street medicine provides high-quality, longitudinal care comparable to that of a primary care clinic, while bridging longstanding gaps in health care access for this marginalized population. This reimbursable model has a simple ethos: we go to the people. This means utilizing a multidisciplinary team, often comprised of medical providers, nurses, community health workers, and social workers to provide comprehensive health care on the street, in patients' lived environments.^9,10 USC Street Medicine has emerged as a leader in the street medicine field, and our approach to address street medicine will be discussed in this piece.

One of the first tools of engagement is harm reduction—providing water, socks, needles, sharps containers, pipes, naloxone, and safe-use information. This builds rapport between the encampment community and the medical team but also opens discussions about substance use, complications of use (abscesses, hypertension, respiratory disease, mental health, etc), and other medical conditions.^9,11

The two most common substances contributing to fatal overdose, methamphetamines and fentanyl, are used socially and have utility on the street, but when used concurrently may provoke a cycle of survival use: methamphetamine to stay awake at night to protect bodies and belongings, fentanyl to endure the physical and emotional pain of living unsheltered, and both to balance the effects of the other.^12,13 The symptoms associated with unsupported cessation of either substance are often incompatible with street life—the profound fatigue from methamphetamine withdrawal leaves the patient vulnerable to their surroundings, and the severity of fentanyl withdrawal without basic necessities (toilet, bed, food, adjunct medications) is intolerable. Their unsheltered status effectively entraps them in a perpetual cycle of survival use.

Opioid Use Disorder Treatment on the Street: Past Options

In the past, when unsheltered patients with opioid use disorder (OUD) sought cessation without methadone, we relied on sublingual (SL) buprenorphine formulations. These present challenges, as patients struggle to hold onto their SL strips or tabs (lost or stolen) and are unable to obtain replacement refills.¹⁴ Sublingual induction strategies also pose major barriers in street settings. Low-dose micro-induction (LDMI) requires ongoing opioid use during a multiday SL buprenorphine escalation that relies on complex dosing schedules. High-dose macro-induction (HDMI) requires patients to abstain from opioids and endure spontaneous withdrawal before rapidly dosing SL buprenorphine, which is often difficult and risks severe or precipitated withdrawal if started prematurely.^14,15,16 First-generation monthly long-acting injectable (LAI) buprenorphine provides stability but historically only after successful SL induction, which is uncommon in street-based care.

Additionally, poor outcomes on the street are accompanied by immense protracted risk. Poor outcomes may not only provoke mistrust in the medication but also fracture the relationship with the street medicine team who serves as the last stable connection to health care. It is important to highlight that the street is not only an unmonitored clinical setting, but also one where patients often do not have access to phones to contact the medical team in the event of clinical worsening and demonstrate resistance to seeking higher level care.

New Approaches to Opioid Use Disorder Treatment on the Street: Patient-Centered Direct-to-Inject

Direct-to-inject (DTI) buprenorphine induction strategies have changed the landscape of OUD treatment on the street by offering patient-centered alternatives that address structural barriers while minimizing withdrawal burden and treatment complexity.

Critical to our approach at USC Street Medicine, we maintain flexibility between two distinct protocols. For patients in mild withdrawal (COWS>4, last use >6 hours ago), a 2-day DTI protocol where the patients abstain from opioid use is initiated. This includes administering a cumulative 24 mg weekly formulation dose (Brixadi) on day 1, followed by a monthly formulation LAI (Brixadi or Sublocade) 24 hours later.^17,18 For patients with recent fentanyl use, a 3-day DTI protocol is initiated, during which patients continue illicit opioid use on days 1 and 2, receiving escalating doses of 8 mg and then 16 mg weekly formulation LAIs (Brixadi), followed by a monthly formulation LAI (Sublocade or Brixadi) with cessation of use on day 3.¹⁹ The pharmacokinetics of the weekly LAI formulations, which reach peak buprenorphine plasma concentration within 24 hours, support gradual receptor occupancy and reduce severe and precipitated withdrawal risk, promoting a more predictable induction model.

Regardless of protocol, we order the same collection of medications to the pharmacy—8 mg and 16 mg weekly formulations and 1 monthly formulation. This allows for adaptation to the patient's needs in real time—administering the 2 weekly formulations together to initiate the 2-day induction if the patient is entering withdrawal or administering 1 injection per day to achieve the 3-day induction if they recently used. We also prescribe adjunct medications to treat withdrawal symptoms, ideally including visual symbols on the prescription bottles for easy indication identification in low-light environments and to encourage appropriate use, for example, a round blue 'moon' sticker on trazodone for insomnia. Supplemental SL buprenorphine may be started 24 hours after the monthly formulation injection to treat any ongoing withdrawal symptoms or cravings which are often present as patients remain in triggering environments. Additionally, patients are offered a first-generation monthly formulation LAI (Sublocade) 8 days after the initial, to overcome the anticipated decline in buprenorphine plasma concentration noted during the first 28 days.²⁰

We recognize there are many emerging DTI protocols, and we have found that offering flexibility between 2 protocols that are adaptable to the patients' presentation and utilize the same combination of prescribed medications increases induction completion and treatment retention. This also promotes collaborative care that is patient centered and trauma informed, which furthers trust with a historically disregarded and traumatized population.²¹

Stimulant Use Disorder on the Street: Available Options

Methamphetamine use is highly prevalent among people experiencing homelessness: one-third report methamphetamine use, and of those who report regular substance use, 90% use methamphetamines.¹³ While illicit stimulants may promote alertness and as such safety on the street, their detrimental health effects are well known, and treatment should be prioritized.²² While there is currently no FDA-approved treatment for stimulant use disorder, contingency management, mirtazapine, bupropion with naltrexone, and GLP-1 receptor agonists have shown promise.^22,23 However, each has important limitations for unsheltered populations. Contingency management requires frequent participation and emphasizes abstinence over harm reduction, creating barriers for people experiencing unsheltered homelessness.^24,25 Mirtazapine may worsen food insecurity and impair alertness through appetite stimulation and sedation.²² Bupropion with naltrexone has modest efficacy and is contraindicated in patients using opioids or receiving agonist therapy.^22,26 GLP-1 receptor agonists present risks in food-insecure populations.

Agonist replacement therapy may offer a novel strategy to treat stimulant use disorder in this population by targeting untreated ADHD.^27,28 ADHD is substantially more prevalent among unsheltered populations than in the general population, with some studies estimating a prevalence approaching one-third.^29,30,31 Many may use illicit stimulants to self-treat symptoms that impair organization, time management, and task completion, all of which complicate completing tasks of daily living and navigating essential resources such as SNAP benefits, identification, disability renewals, and health insurance.³²

While various amphetamine salts have been studied, in a street environment lisdexamphetamine is first-line; as a prodrug it has lower diversion potential and offers a long-acting steady effect without the rapid peaks and troughs of methamphetamine use.^28,33 Monitoring is relatively simple, requiring vital sign checks, serial assessments, and prescription monitoring. Among unsheltered patients with untreated ADHD, we have observed substantial reductions and successful cessation of methamphetamine use following initiation of this approach.

Looking Forward

People experiencing unsheltered homelessness are the most vulnerable and understudied population in addiction medicine. We are in dire need of rapid expansion of research on effective interventions, as well as rapid policy and infrastructure changes to improve access to addiction services. This is especially concerning in light of upcoming Medicaid changes, including the 80-hour-per-month work requirement under H.R.1, which will result in many people experiencing homelessness losing their health insurance, including those who qualify for exemptions.^34,35 Although people with substance use disorders qualify for the "medical frailty" exemption, maintaining coverage will require documentation from a provider or treatment program at least every 6 months. For people experiencing homelessness, these administrative requirements will add major barriers and likely lead to insurance lapses. Once coverage is lost, re-establishing care and documentation of exemptions becomes more difficult, further limiting access to life-saving treatment, like buprenorphine, and worsening an already devastating mortality crisis. Unsheltered patients are seen across all clinical settings, and improving outcomes will require urgent investment in compassionate, low-barrier addiction services that recognize survival on the street as a profound medical vulnerability deserving of sustained support and care.