A Naturalistic Study on the Combined Neural and Psychological Effects of Psilocybin and Compassion Focused Imagery

Combining psilocybin with a compassion-focused imagery exercise produces long-term synergistic effects on cognitive absorption, self-compassion, and decentering. In a sample of 105 participants, those who received a compassion imagery prime before taking psilocybin showed distinct changes in brain network interactions—particularly among attentional, executive, and default mode networks—compared to those who simply focused on breathing. fMRI-based classifiers could distinguish the two priming conditions only at a high dose of psilocybin. The findings suggest that pairing psilocybin with compassion-based practices may amplify lasting psychological shifts and reorganize large-scale brain networks, though confirmatory studies are needed.

Study at a glance

Abstract

Abstract Psilocybin is a classic psychedelic drug known to alter subjective experience and elicit long-term psychological changes, enhancing cognitive flexibility and reducing rigid self-related beliefs. Combined with compassion motivational primes that involve generating mental representations of compassion, it may increase the potential for activating the care-affiliative motivational systems, linked to several important biopsychosocial processes underpinning social safeness, social connection and mental wellbeing. We investigated the synergetic effects of psilocybin and compassion imagery with self-reported questionnaires and functional resonance imaging data (fMRI) in a sample of 105 participants. Participants were primed with either attention to breathing or a short compassion focused imagery prime. We found a long-term synergetic effect of compassion imagery and psilocybin on cognitive absorption, as well as changes relative to baseline self-compassion and decentering. Based on functional interactions between attentional, executive and default mode networks, fMRI-based classifiers detected participant engagement in compassion focused imagery before psilocybin intake and distinguished compassion imagery vs. attention to breathing priming only the high dose of psilocybin. Our results support the potential for synergistic effects from combinations of psilocybin and compassion-based interventions to induce long-term psychological changes, reshaping the functional organization of large-scale brain networks. Future confirmatory studies of our exploratory analyses should be conducted to determine whether the combination of psilocybin and compassion-based practices promotes increases in caring and contemplative abilities, enhanced psychological flexibility and well-being.