<p>Psychoactive substances are unruly, wobbly, and mercurial in ways that trip up grammars designed to control, anticipate, and harness them. We explore how frameworks of 'context-dependency' and 'set and setting' struggle to handle such unruliness, even as they have become programmatic for understanding psychoactive effects across clinical psychiatry, harm reduction practices, Indigenous eco-cosmologies, the history of churches, and more. Moving beyond mechanistic notions of interaction effects and a deterministic science of context, we import the concept of attunement from the critical humanities to reclaim and uplift the trickery and the fickleness of substances misapprehended as controlled technologies with predictable outcomes. We trace this through the contextual and affective governance of psychedelic medicalisation, alongside the illuminating literature on the Indigenous Amazonian brew ayahuasca. Considering how ayahuasca resonates across ancestral, counter-colonial, and capitalistic fields of attunement that render experience multiple and indeterminate, we show how the fields themselves vibrate, condense, melt, overlap, and transform through bodily and sensory experience. This matters at a time when psychedelics are being rapidly pulled into medical, market-based, and infrastructural pathways that risk tuning them to a narrow band of possibility.</p>