Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation.

In this study, for the first time, we explored a dataset of functional magnetic resonance images collected during focused attention and open monitoring meditation before and after a five-day psilocybin-assisted meditation retreat using a recently established approach, based on the Mapper algorithm from topological data analysis. After generating subject-specific maps for two groups (psilocybin vs. placebo, 18 subjects/group) of experienced meditators, organizational principles were uncovered using graph topological tools, including the optimal transport (OT) distance, a geometrically rich measure of similarity between brain activity patterns. This revealed characteristics of the topology (i.e. shape) in space (i.e. abstract space of voxels) and time dimension of whole-brain activity patterns during different styles of meditation and psilocybin-induced alterations. Most interestingly, we found that (psilocybin-induced) positive derealization, which fosters insightfulness specifically when accompanied by enhanced open-monitoring meditation, was linked to the OT distance between open-monitoring and resting state. Our findings suggest that enhanced meta-awareness through meditation practice in experienced meditators combined with potential psilocybin-induced positive alterations in perception mediate insightfulness. Together, these findings provide a novel perspective on meditation and psychedelics that may reveal potential novel brain markers for positive synergistic effects between mindfulness practices and psilocybin.

Home treatment as an add-on to family-based treatment for adolescents with anorexia nervosa compared with standard family-based treatment and home-based stress reduction training: study protocol for a randomized clinical trial.

BACKGROUND: Family-based treatment (FBT) is currently the most effective evidence-based treatment approach for adolescents with anorexia nervosa (AN). Home treatment (HT) as an add-on to FBT (FBT-HT) has been shown to be acceptable, feasible and effective. The described three-arm randomized clinical trial (RCT) is intended to investigate whether FBT-HT demonstrates higher efficacy compared to standard outpatient FBT with supplemental mindfulness-based stress reduction training (FBT-MBSR). METHODS: This RCT compares FBT-HT to standard outpatient FBT and FBT-MBSR as a credible home-based control group in terms of efficacy and delivery. Adolescents with AN or atypical AN disorder (n = 90) and their parent(s)/caregiver(s) are to be randomly assigned to either FBT, FBT-HT or FBT-MBSR groups. Eating disorder diagnosis and symptomatology are to be assessed by eating disorder professionals using standardized questionnaires and diagnostic instruments (Eating Disorder Examination, Eating Disorder Inventory, Body Mass Index). In addition, parents and caregivers independently provide information on eating behavior, intrafamily communication, stress experience and weight. The therapeutic process of the three treatments is to be measured and assessed among both participants and care providers. The feasibility, acceptability and appropriateness can thus also be evaluated. DISCUSSION: We hypothesize that FBT-HT will be an acceptable, appropriate and feasible intervention and, importantly, will outperform both established FBT and FBT-MBSR in improving adolescent weight and negative eating habits. Secondary outcome measures include the reduction in the stress experienced by caregivers, as well as the regulation of perceived expressed emotions within the family, while the intrafamily relationships are hypothesized to mediate/moderate the effectiveness of FBT. The proposed study has the potential to enhance the scientific and clinical understanding of the efficacy of FBT for AN, including whether the addition of HT to FBT versus another home-based adjunct intervention improves treatment outcomes. Furthermore, the study aligns with public health priorities to optimize the outcomes of evidence-based treatments and integrate the community setting. Trial registration This study is registered at ClinicalTrials.gov (NCT05418075).

Comparing Neural Correlates of Consciousness: From Psychedelics to Hypnosis and Meditation.

BACKGROUND: Pharmacological and nonpharmacological methods of inducing altered states of consciousness (ASCs) are becoming increasingly relevant in the treatment of psychiatric disorders. While comparisons between them are often drawn, to date no study has directly compared their neural correlates. METHODS: To address this knowledge gap, we directly compared 2 pharmacological methods (psilocybin 0.2 mg/kg orally [n = 23] and lysergic acid diethylamide [LSD] 100 µg orally [n = 25]) and 2 nonpharmacological methods (hypnosis [n = 30] and meditation [n = 29]) using resting-state functional connectivity magnetic resonance imaging and assessed the predictive value of the data using a machine learning approach. RESULTS: We found that 1) no network reached significance in all 4 ASC methods; 2) pharmacological and nonpharmacological interventions of inducing ASCs showed distinct connectivity patterns that were predictive at the individual level; 3) hypnosis and meditation showed differences in functional connectivity when compared directly and also drove distinct differences when jointly compared with the pharmacological ASC interventions; and 4) psilocybin and LSD showed no differences in functional connectivity when directly compared with each other, but they did show distinct behavioral-neural relationships. CONCLUSIONS: Overall, these results extend our understanding of the mechanisms of action of ASCs and highlight the importance of exploring how these effects can be leveraged in the treatment of psychiatric disorders.

Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat.

Meditation and psychedelics have played key roles in humankind's search for self-transcendence and personal change. However, neither their possible synergistic effects, nor related state and trait predictors have been experimentally studied. To elucidate these issues, we administered double-blind the model psychedelic drug psilocybin (315 µg/kg PO) or placebo to meditators (n = 39) during a 5-day mindfulness group retreat. Psilocybin increased meditation depth and incidence of positively experienced self-dissolution along the perception-hallucination continuum, without concomitant anxiety. Openness, optimism, and emotional reappraisal were predictors of the acute response. Compared with placebo, psilocybin enhanced post-intervention mindfulness and produced larger positive changes in psychosocial functioning at a 4-month follow-up, which were corroborated by external ratings, and associated with magnitude of acute self-dissolution experience. Meditation seems to enhance psilocybin's positive effects while counteracting possible dysphoric responses. These findings highlight the interactions between non-pharmacological and pharmacological factors, and the role of emotion/attention regulation in shaping the experiential quality of psychedelic states, as well as the experience of selflessness as a modulator of behavior and attitudes. A better comprehension of mechanisms underlying most beneficial psychedelic experiences may guide therapeutic interventions across numerous mental conditions in the form of psychedelic-assisted applications.

Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects.

Both psychedelics and meditation exert profound modulatory effects on consciousness, perception and cognition, but their combined, possibly synergistic effects on neurobiology are unknown. Accordingly, we conducted a randomized, double-blind, placebo-controlled study with 38 participants following a single administration of the psychedelic psilocybin (315 µg/kg p.o.) during a 5-day mindfulness retreat. Brain dynamics were quantified directly pre- and post-intervention by functional magnetic resonance imaging during the resting state and two meditation forms. The analysis of functional connectivity identified psilocybin-related and mental state-dependent alterations in self-referential processing regions of the default mode network (DMN). Notably, decoupling of medial prefrontal and posterior cingulate cortices, which is thought to mediate sense of self, was associated with the subjective ego dissolution effect during the psilocybin-assisted mindfulness session. The extent of ego dissolution and brain connectivity predicted positive changes in psycho-social functioning of participants 4 months later. Psilocybin, combined with meditation, facilitated neurodynamic modulations in self-referential networks, subserving the process of meditation by acting along the anterior-posterior DMN connection. The study highlights the link between altered self-experience and subsequent behavioral changes. Understanding how interventions facilitate transformative experiences may open novel therapeutic perspectives. Insights into the biology of discrete mental states foster our understanding of non-ordinary forms of human self-consciousness and their concomitant brain substrate.