Background <p>Major depression is a prevalent condition among patients with life-threatening illnesses, such as cancer, and recent findings suggest that psilocybin may hold promising treatment potential. Contemporary trials of psilocybin generally employ a model that includes psychotherapeutic support consisting of preparation and integration sessions surrounding the dosing. However, there is limited research on the psychotherapeutic component of treatment, including the skills, professional qualifications and training needed to provide it.</p> Methods <p>In this study, nine nurses completed a 15-week online and on-site training program as facilitators in an ongoing randomized controlled trial of psilocybin treatment for depression. The training evaluation consisted of a subjective evaluation by the facilitators collected during and after completion of training, and an objective evaluation of the facilitators’ verbal relational skills assessed with standardized role-plays before and after completion of training. The recorded role-plays were assessed using the relational components of the Motivational Interviewing Treatment Integrity (MITI) code 4.2 and analyzed with the Wilcoxon Signed Rank Test.</p> Results <p>The facilitators’ subjective evaluations indicated that the online and on-site training sessions had supported their knowledge- and skill acquisition. However, most facilitators reported that additional practical in-person training would have been necessary for them to feel adequately prepared to provide the treatment. The objective assessment of the facilitators’ verbal relational skills showed a significant increase in one of twelve MITI variables and medium to large effect sizes for six of the measures pre- to post-training.</p> Conclusions <p>The training model used in this study showed potential to improve outcomes, though effects were modest and only demonstrated in role-play. The facilitators also indicated a need for additional training to feel adequately prepared. The exact requirements for the psychotherapeutic support surrounding the dosing in these treatments, including the specific skills and professional qualifications needed to provide it, remain unclear. Nonetheless, the results of this study suggest that different professionals may require distinct types of training to deliver these treatments effectively. Future studies should design training programs based on the facilitators’ baseline skills and provide clear descriptions and objective measures of both the training intervention and outcome, along with adherence measures throughout treatment.</p> Trial registration <p>EudraCT: 2023-505532-35-00; Clinicaltrails.gov ID: NCT06319378. Registered 8 November 2023.</p>