Abstract Background and aims There is an urgent unmet need for novel treatments for methamphetamine (MA) use disorder. We explored the qualitative experiences of people participating in a study of psilocybin‐assisted psychotherapy (PAT) to treat MA use disorder. Design and setting Qualitative study of participants enrolled in a single arm, open‐label pilot study of PAT for MA use disorder delivered in an outpatient stimulant treatment program setting in Sydney, Australia. Participants Twelve participants were interviewed before starting PAT and then again one month following PAT. Measurements Pre‐PAT interviews explored participants' experiences of MA use and expectations of receiving PAT. Post‐PAT interviews explored participants' experiences of PAT, with a focus on phenomena related to the acute subjective effects of psilocybin, the perceived effects of PAT on MA use, self‐perception, beliefs, values, behaviours, interpersonal relationships and spirituality, and acceptability of the intervention. Interviews were audio recorded, transcribed verbatim and analysed using an inductive qualitative approach. Findings While participants generally hoped to have positive outcomes from study participation, their expectations were generally tempered and realistic. Their trial experiences of PAT were often characterised by new understandings of themselves, their narrative histories and interpersonal relationships, all of which were frequently prompted by leaning into vividly presented challenging experiences within the psychedelic experience. This volitional attitude of ‘leaning into the obstacle’ emerged as a key theme, meriting exploration for its potential to expose the subjective dimension of the psychedelic mechanism of effect. Resolution of this obstacle was associated with a reduction in the salience of methamphetamine. Therapeutic alliance was seen as critical to positive outcomes and was achieved through high levels of concentrated therapeutic attention and intersubjective intimacy between participant and therapist. Conclusions Interviewed participants in a study of psilocybin‐assisted psychotherapy (PAT) for methamphetamine use disorder perceived PAT as an acceptable intervention. Transformation in understandings of self and interpersonal relationships and subsequent reduced salience of methamphetamine use often occurred through confronting psychic obstacles in the context of high levels of therapeutic support from study therapists.