Meditation as a Bioactive Intervention: Molecular and Neurophysiological Mechanisms Revealed by Connectivity Mapping
Aditi Joshi, Deep Patel, Vignesh Muralidharan, Mitali Mukerji
bioRxiv December 29, 2025 preprint DOI: 10.64898/2025.12.27.696659 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Secondary analysis of clinical trial RNA sequencing data with meta-analysis |
|---|---|
| Sample size | 106 |
| Population | Participants in a clinical trial practicing inner engineering meditation |
| Intervention | Inner engineering meditation |
| Measures | Connectivity Map (CMap), RNA sequencing, transcranial magnetic stimulation (TMS-EMG and TMS-EEG), multiple correspondence analysis |
| Topics | Meditation |
| Key findings | Meditation-induced molecular signatures overlapped with over 438 drugs, predominantly those targeting neuroactive ligand receptor pathways and modulating excitation-inhibition balance. The authors argue that meditation's effects mimic drugs acting on GABAergic, glutamatergic, and other neuromodulatory pathways, supporting a view of meditation as a biologically active intervention rather than solely a psychological practice. |
Abstract
Meditation practices are often used as non-pharmacological adjunct therapy for managing stress and well-being benefits. We propose that beneath their non-pharmacological facade, meditation practices might operate via drug target modulation having profound neurophysiological effects. Firstly, we leverage the Connectivity Map (CMap) to investigate (a) the overlap between meditation-induced molecular signatures and established drug responses, and (b) the pathways and mechanisms contributing to meditation’ potential therapeutic effects. This was studied in a comprehensive temporal RNAseq dataset comprising premeditation, meditation, and follow-up stages from a clinical trial involving 106 participants practising inner engineering meditation. Meditation signatures overlapped with over 438 drugs, but predominantly with drugs targeting the neuroactive ligand receptor pathways, capable of modulating the brain’s excitation-inhibition (E/I) balance. Next, to bridge the meditation-induced molecular changes to measurable neurophysiological effects, we performed a comprehensive meta-analysis of drugs affecting E/I balance through the lens of non-invasive brain stimulation, i.e., transcranial magnetic stimulation (TMS-EMG and TMS-EEG). Using multiple correspondence analysis, we then clustered the CMap informed neuroactive drugs and their E/I effects on the same latent space. We found that meditation’s effects mimic drugs targeting the GABAergic, Glutametergic and other neuromodulatory system pathways. Our findings lead to a working model to objectively test neurophysiological changes resulting from meditation that can lead to evidence-based clinical applications. Overall, these findings support the view that meditation acts as a biologically active intervention capable of modulating molecular pathways and cortical excitability, rather than functioning solely as a psychological or contemplative practice.
Comparable studies
Other systematic reviews and meta-analyses on meditation, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Meditation Programs for Psychological Stress and Well-being Diverse adult clinical populations | 2014 | Meta-analysis | n = 3,515 |
| Mindfulness-Based Stress Reduction for Stress Management in Healthy People: A Review and Meta-Analysis Healthy subjects | 2009 | Systematic review and meta-analysis | |
| The psychological effects of meditation: A meta-analysis. Nonclinical groups of adult meditators | 2012 | Meta-analysis | n = 163 |
| Efficacy of Mindfulness-Based Cognitive Therapy in Prevention of Depressive Relapse Adults with recurrent depression in full or partial remission | 2016 | Meta-analysis of individual patient data from randomized controlled trials | n = 1,258 |
| Mindfulness‐Based Stress Reduction and Mindfulness‐Based Cognitive Therapy – a systematic review of randomized controlled trials | 2011 | Systematic review |
Citations in the library
Cites 9
- The varieties of contemplative experience: A mixed-methods study of meditation-related challenges in Western Buddhists PLoS One May 24, 2017
- Unwanted effects: Is there a negative side of meditation? A multicentre survey PLoS One September 5, 2017
- Mindfulness is associated with intrinsic functional connectivity between default mode and salience networks Frontiers in Human Neuroscience August 25, 2015
- Isha Yoga Practices and Participation in Samyama Program are Associated with Reduced HbA1C and Systemic Inflammation, Improved Lipid Profile, and Short-Term and Sustained Improvement in Mental Health: A Prospective Observational Study of Meditators Frontiers in Psychology May 19, 2021
- Meditation-Induced Psychosis: Trigger and Recurrence Case Reports in Psychiatry August 13, 2021
and 4 more in the library