Queer theory makes a rather polarized distinction between pleasures of self-confirmation and pleasures of self-shattering, plaisir and jouissance. But pleasure can be approached as a conjunctural event in which new objects, attachments, identities, and ways of relating to the world emerge. Standard conventions in drug research remain unmoved by pleasure, consigning it to irrelevance, minimizing its significance or otherwise disregarding it. Thinking with pleasure is different from thinking about pleasure, thinking against it, or even thinking through it. It foregrounds the relation between the researcher and researched, proposing that each party has the capacity to affect and be affected by the other in surprising and potentially generative ways. While this creates some symmetry between the practices of the researcher and the practices of the researched, it does not confuse their respective projects. Each is engaged in their own process of self-transformation, though in each case established habits of practice and thought are put to the test in an encounter that creates the conditions for new ways of feeling and doing and being to emerge. Drug practices are often said to be motivated by a desire for self-loss, but this is not the same as a death wish. Concerns about safety inform the design of people’s experiments with drug use – experiments which also, incidentally, put techniques of reducing risk (among other procedures) to the test. Thinking with pleasure confers agentive capacities on research participants, while directing attention to the sociomaterial arrangements that constitute the infrastructure of their experiments and the criteria of value they employ to make sense of them. If care services find better ways of articulating with the everyday concerns and experimental arrangements people put in place to benefit from using drugs, new prospects for health, care, wellbeing and safer drug use might emerge.