Lasting increases in trait mindfulness after psilocybin correlate positively with the mystical-type experience in healthy individuals

Abstract

BackgroundPsilocybin-induced mystical-type experiences are associated with lasting positive psychological outcomes. Recent studies indicate that trait mindfulness is increased 3 months after psilocybin intake, preceded by decreases in neocortical serotonin 2A receptor (5-HT2AR) binding. However, the association between psilocybin-induced mystical-type experiences and subsequent changes in trait mindfulness remains unexplored, as does the association between pre-drug trait mindfulness and 5-HT2AR binding in the healthy brain.AimWe evaluated whether psilocybin induced lasting increases in trait mindfulness in healthy volunteers, and whether the mystical-type experience was associated with this increase. We further examined the association between pre-drug trait mindfulness and 5-HT2AR binding in neocortex and selected frontolimbic regions.Materials and methodsForty-six medium-high dose psilocybin sessions were conducted in 39 healthy individuals. The mystical-type experience was measured with the Mystical Experience Questionnaire (MEQ) at the end of the session. Trait mindfulness was measured using the Mindful Attention and Awareness Scale (MAAS) at baseline and 3 months after the psilocybin session. Thirty-two of the participants completed pre-drug [11C]-Cimbi-36 positron emission tomography (PET) to assess 5-HT2AR binding in neocortex and, post-hoc, in the frontolimbic regions amygdala, frontal cortex, and anterior cingulate cortex.ResultsThe MAAS score was significantly increased at 3-month follow-up (p = 3.24 × 10–6), a change positively associated with the MEQ score (p = 0.035). Although the association between pre-drug MAAS score and neocortex 5-HT2AR binding was not significant (p = 0.24), post-hoc analyses revealed a significant negative association between MAAS and right amygdala 5-HT2AR binding (pFWER = 0.008).ConclusionWe here show that lasting changes in trait mindfulness following psilocybin administration are positively associated with intensity of the mystical-type experience, suggesting that the acute phenomenology of psilocybin facilitates a shift in awareness conducive for mindful living. We furthermore show that higher pre-drug trait mindfulness is associated with reduced 5-HT2AR binding in the right amygdala.

On serotonin, psychedelics, entactogens and psychoplastogens in depression, anxiety, post-traumatic stress, and related disorders.

“…The indications range across an entire spectrum of MDD/TRD, PTSD, GAD, bipolar disorders, pain, substance use and eating disorders, late-stage cancer-related anxiety and depression, autism spectrum disorders and the list keeps increasing. There are multiple generally small scale clinical trials in healthy volunteers or in various indications with psychedelics either as mostly psychological support-assisted monotherapies (Kaelen et al, 2015;Carhart-Harris et al, 2015;2018;Erritzoe et al, 2018;Stroud et al, 2018;Agin-Liebes et al, 2020;Hutten et al, 2020;Mertens et al, 2020;Pokorny et al, 2020;Madsen et al, 2020;Uthaug et al, 2020;Davis et al, 2020;Preller et al, 2020;Spriggs et al, 2020;Verrous et al, 2021;Kaertner et al, 2021;Douglass et al, 2022;Bosch et al, 2022;Duerler et al, 2020;Holze et al, 2021;Family et al, 2020;Müller et al, 2022;Sondergaard et al, 2022;Rucker et al, 2022;Jensen et al, 2022;Burmester et al, 2023;Allen et al, 2024;Eckernas et al, 2023;Good et al, 2023;Ledwos et al, 2023;Mason et al, 2023;Vogt et al, 2023;von Rotz et al, 2023) or as combinations with other psychedelics/entactogens (de Win et al, 2006;Carhart-Harris et al, 2014;Vizeli et al, 2022;Borissova et al, 2024;Heresco-Levy and Lerer, 2023;…”

“…It is established now that some 5-HT 2A receptor agonists promote neuroplasticity, synapse maturation (whereas others do not) and hence have been named psychoplastogens/entactogens (Olson, 2018;Vargas et al, 2021;Ly et al, 2021;Nichols, 2022;Heifetz and Olson, 2023;Ogelman et al, 2024). It is being debated whether the psychedelic trip is needed for the rapid antidepressant effect of psychedelics, and although the answer can only come from clinical studies, there are clear efforts to develop psilocybin and other psychedelic-related molecules devoid of the psychedelic trip/experience-like effect (Cameron and Olson, 2022;Madsen et al, 2021;Sondergaard et al, 2022;Cameron et al, 2023;Siva et al, 2024;Hashimoto, 2024). Such analogues have been synthesised and characterised in preclinical models, where they do not produce the head twitch response (HTR) which is characteristic of the classical psychedelics (Halberstadt et al, 2018(Halberstadt et al, , 2019(Halberstadt et al, , 2020, whereas they sustain rapid antidepressant effects and promote neuronal growth in rodent models (Olson, 2018(Olson, , 2022Ly et al, 2021;Grieco et al, 2022;Kwan et al, 2022).…”

Subacute effects of a single dose of psilocybin on biomarkers of inflammation in healthy humans: An open-label preliminary investigation

“…Sixteen healthy participants were recruited through an online survey (demographics are shown in Table 1 ). Data acquired from these participants were also included in previously published neuroimaging studies unrelated to the topic of this paper, including data from positron emission tomography (PET) and functional magnetic resonance imaging [ 8 , 16 , [34] , [35] , [36] ]. After receiving a detailed description of the study, participants provided written informed consent and subsequently underwent a screening interview and a medical examination.…”

Primary States of Consciousness: A Review of Historical and Contemporary Developments

“…Indeed, mystical experiences has been the subject of extensive research in recent years (Beauregard and Paquette 2006;Stein 2018;Søndergaard et al 2022). Interestingly, the phenomenon of thought-action fusion discussed previously correlates with religiosity (Eric Rassin et al 1999;E.…”