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

Carla Pallavicini, Lorena Llobenes, Federico Cavanna, Laura Alethia de la Fuente, Stephanie Müller, Maria Ileana Costa, Natali Gumiy, Nicolás Bruno, Tomas D'Amelio, Jaskaran Basran, Ptarmigan Plowright, Ain Stolkiner, Mauro Namías, Paul Gilbert, Enzo Tagliazucchi

bioRxiv (Cold Spring Harbor Laboratory) December 22, 2025 preprint DOI: 10.64898/2025.12.17.694940 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study
Sample size 105
Population Human participants
Interventions Psilocybin Compassion-focused imagery
Topics Default mode network Meditation Psilocybin
Keywords Cognition Psychological intervention Compassion Cognitive psychology Hallucinogen Mental image Empathy Consciousness Precuneus Guided imagery Clinical psychology Psychotherapist
Data Zenodo
Key findings Combining psilocybin with compassion-focused imagery, compared to attention to breathing, produced long-term synergistic effects on cognitive absorption, self-compassion, and decentering, and fMRI classifiers distinguished the two priming conditions only at a high dose of psilocybin.

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.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • State of the evidence: Psilocybin and meditation Supports

    Combining psilocybin with compassion-focused imagery versus attention to breathing produced long-term synergistic effects on cognitive absorption, self-compassion, and decentering.

    Synthesized

Comparable studies

Other experimental studies on psilocybin, most cited first.

Study Year Design Participants
Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers 1998 Experimental study
Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Participants in controlled laboratory experiments receiving a moderate to high oral... 2015 Validation study using pooled data from five laboratory experiments n = 184
Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants 2013 Experimental study
Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer Participants with cancer-related psychiatric distress who completed a parent randomized... 2020 Long-term within-subjects follow-up analysis n = 15
Enzymatic Synthesis of Psilocybin 2017 Laboratory study

Citations in the library

Cites 48

and 43 more in the library

Related reading

Explore topics

Default mode network Meditation Psilocybin

By condition and practice

Psilocybin and meditation