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Upstream Overdose Prevention: Why the US Should Pilot a Safer, Regulated Drug Supply
Tessa L Rife-Pennington1,2,3, Katherine Hill4, Claire M Zagorski5
1Pharmacy Service, San Francisco VA Health Care System, CA, USA.
Substance Use & Addiction Journal
|July 14, 2026
Summary
The US overdose crisis demands a safer, regulated drug supply to reduce harm from contaminated illicit drugs. Piloting this approach can improve health and social stability for people who use drugs (PWUD).
Area of Science:
- Public Health
- Substance Use Policy
- Harm Reduction
Background:
- The US overdose crisis is fueled by an unpredictable and contaminated drug supply, including fentanyl, xylazine, and nitazenes.
- Current drug checking interventions place the safety burden on individuals and programs after drugs enter the unregulated market.
Purpose of the Study:
- To advocate for a pragmatic, upstream public health response by authorizing pilots of a safer, regulated drug supply.
- To explore international models and propose a US-specific portfolio approach for regulated drug access.
Main Methods:
- Review of international safer supply models (Switzerland, Canada, UK).
- Proposal for a US-based portfolio approach including healthcare-based pilots and community-governed models.
- Addressing concerns and outlining guardrails for PWUD-led, nonpunitive evaluation.
Main Results:
- International experience suggests safer supply models are feasible and can improve health and social stability.
- Potential benefits include reduced reliance on unregulated supply and decreased acute care utilization.
- A US portfolio approach can leverage existing infrastructure while accommodating community-led initiatives.
Conclusions:
- Authorizing safer supply pilots is a critical policy action to address the overdose crisis.
- Establishing legal protections, funding evaluation, and scaling successful models are essential.
- Integrating safer supply with harm reduction and treatment services can demonstrably reduce drug-related harm.
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