The increasing availability of synthetic opioids such as fentanyl poses new challenges for primary care–based opioid substitution treatment (OST). Traditional supervised dosing models can be resource-intensive and may create barriers for younger patients with emerging opioid use disorder (OUD). Long-acting buprenorphine depot formulations offer a promising alternative for a safe provision and low barrier access to OST. Buprenorphine—particularly when delivered via long-acting depot formulations—may reduce fentanyl-induced respiratory depression due to its high μ-opioid receptor affinity, partial agonism, and stable plasma levels. Evidence from studies suggests that adequate buprenorphine receptor occupancy can attenuate respiratory depression caused by fentanyl. However, real-world data from primary care settings remain limited.A practice-based reflection was conducted using a combination of case-based observations, team discussions, and informal patient feedback gathered over a six-month implementation period. Key domains included clinical safety, workflow integration, patient engagement, and perceived impact on treatment adherence.To reflect on the introduction of depot buprenorphine in a general practice setting, identify barriers and facilitators, and derive practice-relevant lessons for improving access and patient safetyThe introduction of depot buprenorphine led to improved medication adherence among patients at risk of fentanyl exposure and reduced concerns about diversion and misuse. The reflective process highlighted the importance of lowering access barriers and adopting a harm-reduction framework within primary care.The growing availability of synthetic opioids increases the risk of fatal overdoses. Depot buprenorphine offers a promising strategy to reduce this risk when implemented in low-threshold primary care settings. However, structural barriers and limited real-world data currently impede broad implementation and equitable coverage.Practice-based reflection demonstrated that implementing long-acting buprenorphine in general practice is feasible, safe, and beneficial for patients with complex opioid use patterns. Adopting a non-paternalistic, harm-reduction–oriented approach can significantly improve the quality and accessibility of OST. These findings may guide other primary care settings facing increasing fentanyl-related risks.