Trip sitting or just sitting? Session facilitators substantially influence psychedelic experiences in clinical trials but not in healthy ones.

Psychedelics' characteristic acute subjective effects predict therapeutic benefits, such as decreases in depression and anxiety. Thus, optimizing treatment involves better understanding which factors shape subjective effects. Session facilitators, who support participants before, during, and after psychedelic administration sessions, form an important part of the setting of these experiences. Yet, the extent to which session facilitators influence participants' acute subjective effects is unknown. To address this gap, we analyzed data from 9 psilocybin administration studies involving 298 participants, 670 dosing sessions, and 60 facilitators-the largest dataset of its kind. Using multilevel models, we examined whether facilitators contributed to variance in participants' acute subjective effects. Results showed that facilitators accounted for negligible variance (0.8 %) in healthy volunteers, but greater variance in clinical samples (13.6 %), after controlling for study and participant differences. These findings reveal that facilitators may play a clinically meaningful role in shaping psychedelic treatment outcomes in patient populations, relative to non-patients, comparable to or exceeding therapist effects in traditional psychotherapy (∼8 %). These results have direct implications for clinical trial design, training protocols, and the implementation of psychedelic treatments as they continue to scale.