Background Drug-related deaths have substantially increased over the past decade in the UK, particularly in Scotland. Co-use of opioids and benzodiazepines (prescribed and/or illicit) is contributing to rising mortality. This study identified motivations in people’s co-use with the aim of informing prescribing and harm reduction interventions to address drug-related deaths. Methods We interviewed 48 people who co-use opioids and benzodiazepines and/or z-drugs (zopiclone and zolpidem) in Glasgow (n = 28), Teesside (n = 10) and Bristol (n = 10). Most participants self-identified as male (n = 37, 77%), white (n = 45, 94%) and had a mean age of 43 years (range: 25–61 years). The majority reported at least one overdose experience, and poor mental health including trauma. Interviews were semi-structured, conducted by an academic and/or peer researcher, and analysed using reflexive thematic analysis. Results Participants’ motivations for co-using mapped onto two interlinked meta-themes: (1) Functional motivations included co-using to augment drug effects, self-medicate or help to generate income. (2) Experiential motivations described participants’ desires to achieve a ‘buzz’ (feeling energised), ‘glow’ (feeling comforted), ‘oblivion’ (escaping trauma and adversity), and ‘gouching’ (physical and mental sensations of ebbing in and out of glow and oblivion). Functional and experiential motivations were dynamic, interrelated and often co-occurred. Conclusions The importance of assessing motivations to co-use should be routinely recognised as part of harm reduction and medication assisted treatments to reduce mortality risk.

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