December 9, 2025
Sebastian Ehmann, Terje Sparby, Vanessa Naughton et al.
preprint
Advanced meditators report profound psychological changes across emotional, cognitive, interpersonal, and existential domains, including vast improvements in baseline well-being, consistently strong positive attitudes, increased positive affect, enhanced mental clarity and attentional stability, positive shifts in life orientation, and transformative changes in mental health conditions. Many described existential insights arising through resolving psychological difficulties, leading to reduced suffering and deeper meaning. Additional themes included synergistic effects between meditation, psychotherapy, and psychedelics. This provides initial empirical evidence that advanced meditation supports profound psychological transformation and reduced suffering.
November 23, 2025
Terje Sparby, Matthew D. Sacchet
preprint
Meditation can lead to advanced meditative endpoints (MEND), often called awakening, enlightenment, or nirvana. Different Buddhist traditions and contemporary mindfulness teachers describe nirvana in conflicting ways: as ultimate reality beyond awareness, as pure awareness itself, as the cessation of suffering, as ultimate happiness, as ineffable, or as paradoxical. These varied views make it difficult to study nirvana scientifically. The authors propose an integrated taxonomy that unifies these perspectives by distinguishing between ways of entering MEND, MEND events, and persistent MEND. This framework provides a starting point for investigating MEND beyond the specific case of nirvana.
October 8, 2025
Sebastian Ehmann, Brian Lord, Erica Cook et al.
preprint
Inhibiting the posterior cingulate cortex with transcranial focused ultrasound during a ten-day silent retreat enhanced meditative qualities such as equanimity, concentration, and sensory clarity. Twenty-eight meditators received two stimulation sessions and reported significant increases in trait mindfulness, nondual awareness, and interoceptive body listening. Qualitative reports showed consistent differences between stimulation and non-stimulation days, including shifts in self-perception and cathartic emotional release. The effects often interacted with participants' ongoing psychological challenges, suggesting tFUS may increase baseline equanimity and support meditative development. Implementation was feasible but required logistical planning; limitations include the quasi-experimental design and reliance on self-reports.
bioRxiv
September 25, 2025
Jakub Vohryzek, Edmundo Lopez-Sola, Winson F.z. Yang et al.
preprint
Advanced concentrative absorption meditation (jhāna) produces a shift in brain dynamics toward near-criticality, a state of heightened flexibility and integration. Using 7T fMRI and whole-brain modeling, the study found that later absorption states, considered minimal phenomenal experiences, show increased large-scale functional integration and a shift of the default mode network from a noise-driven regime to near-critical dynamics. This near-critical regime is interpreted as a form of openness, where constrained brain activity gives way to greater flexibility, correlating with broader attention and reduced narrative thought. The trajectory of these states is non-linear, with major reconfigurations at key meditative milestones.
medRxiv
July 29, 2025
Yuwen He, Shan Lei, Wangli Si et al.
preprint
Mindfulness meditation training alters functional connectivity in the somatomotor network (SMN) in both healthy and depressed populations. In 51 healthy and 35 depressed participants, common changes involved SMN-attentional network connections, suggesting that training modulates attention through somatic awareness. Population-specific changes also emerged: healthy individuals showed SMN-subcortical network shifts, indicating more pervasive effects on automatic processes, while depressed individuals showed SMN-default mode network interactions, which may explain why mindfulness is effective for depression. These altered connectivity patterns significantly predicted insomnia improvements after training in both groups, highlighting shared and distinct neural mechanisms underlying mindfulness-related mental health benefits.
December 26, 2024
Idil Sezer, Matthew D. Sacchet
preprint
Meditation's effects on the autonomic nervous system (ANS) are inconsistent across studies, with reports of both sympathetic and parasympathetic activation, sympathetic-only, parasympathetic-only, or temporally variable patterns. This review synthesizes these heterogeneous findings by considering three explanatory factors: type of meditation, meditator expertise level, and intra-individual variations within a practice. Considering these factors reveals convergent patterns, shifting from the broad notion of 'long-term' meditation to a more precise characterization of 'advanced' meditation, highlighting skills, states, and stages of mastery. The synthesis identifies specific heart rate variability patterns, including very low and low-frequency spectral power peaks, along with cardiac and respiratory coupling, which can inform improved meditation training.
European Psychiatry
April 1, 2024
A. M. Klassen, C.t.m. Baten, J. H. Shepherd et al.
Repeated-dose intravenous ketamine is an effective rapid-acting treatment for treatment-resistant depression. In a large-scale analysis of 1,182 participants across 51 primary studies, intravenous ketamine produced statistically significant reductions in depression symptoms compared to placebo and other control conditions, as measured by standardized clinician and self-report scales. The findings provide quantitative support for ketamine's effectiveness in treatment-resistant depression and highlight variations in treatment parameters across the literature.
European Psychiatry
April 1, 2024
J. H. Shepherd, A. Hickman, C.t.m. Baten et al.
Acute ketamine administration alters neural activation in multiple cortical and subcortical regions in healthy people, as shown by a meta-analysis of 18 fMRI studies with 306 participants. The analysis used multilevel kernel density analysis and ensemble thresholding to minimize bias. These findings help map the functional neuroanatomical effects of ketamine, which may inform its therapeutic use for psychiatric and neurological conditions. Future research should examine both short- and long-term neural effects in clinical populations.
November 22, 2023
Rosalind McAlpine, Katarina Krajnović, Maisha M. Khan et al.
preprint
A self-directed, 21-day digital course (Digital Intervention for Psychedelic Preparation, DIPP) was developed to help people prepare for psychedelic experiences. The course is based on a four-factor model of psychedelic preparedness: Knowledge-Expectation, Psychophysical-Readiness, Safety-Planning, and Intention-Preparation. It includes daily meditation, weekly exercises, and mood tracking. Development followed the UK Medical Research Council framework for complex interventions and used a person-centred, co-design approach. Interviews with 19 past retreat attendees and co-design workshops with 28 current retreat attendees shaped the intervention. DIPP offers a scalable, digital solution to enhance preparedness, aiming to limit adverse reactions and improve therapeutic benefits.
European Psychiatry
March 1, 2023
J. H. Shepherd, C.t.m. Baten, A. C. Klassen et al.
Serotonergic psychedelics such as LSD, psilocybin, and MDMA significantly alter neural activation in several regions of the cerebral cortex and basal ganglia. Some effects are common across these drugs, while others are unique to each substance. This meta-analysis combined functional MRI studies of both clinical and healthy participants, using multilevel kernel density analysis with ensemble thresholding. The findings clarify the functional neuroanatomy associated with these drugs and may guide future research into their therapeutic and adverse effects, particularly for emerging psychiatric treatments.