BACKGROUND: Negative perceptions of psilocybin and challenges of participant enrollment may represent barriers to conducting a randomized controlled trial examining psilocybin for chronic neuropathic pain. AIM: Prior to trial initiation, we aimed to examine patient attitudes toward the trial via a prospective preference assessment. METHODS: Twenty-six patients with chronic neuropathic pain participated in a prospective preference assessment comprising quantitative (survey) and qualitative (interview) components. Content analysis was used to inductively and deductively identify factors that would motivate or discourage participation in the proposed trial. Demographics, clinical characteristics, and perceptions of psilocybin were collected to explore differences in characteristics between patients who were willing and unwilling to participate. RESULTS: Survey results showed that most participants (76.9%) were willing to participate in the PEACE-PAIN trial. "Willing" participants reported higher prior psychedelic use (75%) as compared to the "maybe willing" (0%) and "not willing" participants (0%). Interviews indicated that the top two factors that motivated participation included the need for new treatment options (31.7%) and benefits to personal pain management (31.7%). The top two discouraging factors included practical difficulties of research participation (16.7%), and adverse events associated with psilocybin (16.7%). CONCLUSIONS: The PEACE-PAIN trial study design is supported by patient survey responses but may benefit from modifications, namely incorporating thorough discussions of the current evidence for efficacy, safety, tolerability, and approaches to address adverse effects of psilocybin. Additionally, the interest in participation by individuals with prior psychedelic use holds important methodological implications for the inclusion/exclusion criteria of the trial.