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A single psilocybin dose is associated with long-term increased mindfulness, preceded by a proportional change in neocortical 5-HT2A receptor binding
Open accessAbstract
A single dose of the serotonin 2A receptor (5-HT2AR) agonist psilocybin can have long-lasting beneficial effects on mood, personality, and potentially on mindfulness, but underlying mechanisms are unknown. Here, we for the first time conduct a study that assesses psilocybin effects on cerebral 5-HT2AR binding with [11 C]Cimbi-36 positron emission tomography (PET) imaging and on personality and mindfulness. Ten healthy and psychedelic-naïve volunteers underwent PET neuroimaging of 5-HT2AR at baseline (BL) and one week (1W) after a single oral dose of psilocybin (0.2-0.3 mg/kg). Personality (NEO PI-R) and mindfulness (MAAS) questionnaires were completed at BL and at three-months follow-up (3M). Paired t-tests revealed statistically significant increases in personality Openness (p uncorrected = 0.04, mean change [95%CI]: 4.2[0.4;∞]), which was hypothesized a priori to increase, and mindfulness (p FWER = 0.02, mean change [95%CI]: 0.5 [0.2;0.7]). Although 5-HT2AR binding at 1W versus BL was similar across individuals (p uncorrected = 0.8, mean change [95%CI]: 0.007 [-0.04;0.06]), a post hoc linear regression analysis showed that change in mindfulness and 5-HT2AR correlated negatively (β [95%CI] = -5.0 [-9.0; -0.9], p FWER= 0.046). In conclusion, we confirm that psilocybin intake is associated with long-term increases in Openness and - as a novel finding - mindfulness, which may be a key element of psilocybin therapy. Cerebral 5-HT2AR binding did not change across individuals but the negative association between changes in 5-HT2AR binding and mindfulness suggests that individual change in 5-HT2AR levels after psilocybin is variable and represents a potential mechanism influencing long-term effects of psilocybin on mindfulness.
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“Moreover, psychedelics have been found to increase trait mindfulness, and the skills of nonjudgement, compassion and non-reactivity [56, 57].”
From Mindfulness meditation and psychedelics: potential synergies and commonalities (2023) · cites this paper as [57]
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“whereas increased mindfulness capacities have been found to persist up to 3 months (43).”
From Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees (2022) · cites this paper as [43]
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“A further psychological process which may be of particular salience when discussing therapeutic efficacy for anxiety, and which psychedelics have been repeatedly found to enhance, are mindfulness capacities (10, 22, 23, 42–46).”
From Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees (2022) · cites this paper as [43]
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“as macrodoses have been associated with increased mindfulness (Madsen et al. 2020;Soler et al. 2016;Uthaug et al. 2019)”
From Psychedelic Microdosing, Mindfulness, and Anxiety: A Cross-Sectional Mediation Study (2023) · cites this paper as Madsen et al. 2020
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Metadata
- Authors
- Madsen, M. K., Fisher, P. M., Stenbæk, D. S., Kristiansen, S., Burmester, D., Lehel, S., Páleníček, T., Kuchař, M., Svarer, C., Ozenne, B., & Knudsen, G. M.
- Affiliations
- University of Copenhagen (DK)
- Copenhagen University Hospital (DK)
- National Institute of Mental Health (CZ)
- Corresponding author
- Knudsen, Gitte M.
- ORCID
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 33
- Pages
- 71-80
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W3009076589
- Cited by
- 183
- References
- 73
- Citations by year
- 2026: 10 · 2025: 29 · 2024: 34 · 2023: 43 · 2022: 27 · 2021: 31 · 2020: 9
- FWCI
- 10.99
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Funders
- Innovation Fund Denmark (4108-00004B)
- Independent Research Fund Denmark (6110-00518B)
- Ester M. og Konrad Kristian Sigurdssons Dyreværnsfond (850-22-55166-17-LNG)
- Rigshospitalet's Research Council (R130-A5324)
- Lundbeck Foundation (F-61171-19-27, R231-2016-3236)
- Horizon 2020 (746850)
- MICR (VI20172020056)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Paranormal Experiences and Beliefs
- Keywords
- psilocybin, mindfulness, personality, openness to experience, neocortex, serotonin receptor agonists, psychedelic therapy
- MeSH terms
- Adult, Benzylamines, Female, Hallucinogens, Humans, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Personality, Personality Tests, Phenethylamines, Psilocybin, Neocortex, Receptor, Serotonin, 5-HT2A, Positron-Emission Tomography, Young Adult, Mindfulness
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