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Over the past decade and a half, psychedelic drug-induced experiences have been returning to psychiatry as promising new healing modalities. The case of psychedelic-assisted psychotherapy can inform how we think about the context of drug use because psychedelics are commonly considered to be sensitive to the ‘[mind] set and setting’ of their use. As such, epistemic and therapeutic concerns among psychedelic researchers and therapists over the importance of set and setting are interwoven. My ethnography of psychedelic therapeutics both inside and outside of the clinical trials on the east coast of the United States from 2015 to 2019 suggests that there are added political and economic imperatives to contain psychedelic use. Working with this insight, I suggest psychedelic researchers and therapists are producing immense experiences that tend to overflow the attempts at their containment. I also identify two qualities central to the set and setting of the emerging modality of psychedelic-assisted psychotherapy. The first is a labor of protecting spaces which reveals an attentiveness to disconnection that can be read as in tension with the more commonly evoked emphasis on connection found within psychedelic discourses. The second is how psychedelic experiences (as ‘mind-manifesting’) are understood to reflect the self, and in so doing re-present epistemic disagreements about the nature of the self thus reflected. Taken together, I propose that these two qualities of psychedelic containment offer an analytics for reading the contemporary cultural politics of psychedelic use.