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It is well-recognised that complex and long-standing connections exist between sexual minoritisation and desires to chemically alter bodily experience. For many LGBTQ people the use of pharmaceutical and recreational drugs can be a creative response to marginalisation, as well as a means of resisting normative regimes of sexuality and gender. Yet despite evidence that rates of drug use are higher among LGBTQ populations, research exploring the gendered and sexual dynamics of substance use among LGBTQ people is limited. Applying concepts from STS and queer theory, and drawing on qualitative interviews from an Australian study, we consider how LGBTQ consumers pursue particular drug effects to transform or enhance their experience of gender and/or sexuality. Our analysis traces the ontologies of sexuality and gender that queer subjects enact in their chemical practices, finding that for many drug use materialises in relation to sex, desire and play where it enhances pleasure, enables transgression and facilitates endurance. In the context of gender variance, our findings suggest that drug use produces new, surprising subjectivities and has a range of benefits, including therapeutic ones such as palliating bodily discomfort, and generating emotional openness and healing. By considering the productive role of drugs in enacting queer identities, this paper treats drugs as technologies of the self and considers how drug use, sex, gender, play and pleasure inform each other across a range of settings. We conclude by considering the implications of these findings for drug policy and harm reduction efforts, and for the making of queer subjects.