Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology.
Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. Mediano, Alex T. Zhao, Katrin H. Preller, Robin Carhart-Harris, Morten L. Kringelbach
Translational Psychiatry December 4, 2024 DOI: 10.1038/s41398-024-03187-1 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Peer reviewed |
|---|---|
| Interventions | LSD psilocybin DMT |
| Topics | Philosophy of mind |
| Keywords | Consciousness Altered states Psychedelics Brain connectivity |
| Citations | 17 |
| Key findings | Psychedelics generally strengthen between-network functional connectivity and weaken within-network functional connectivity, with LSD producing stronger visionary restructuring than psilocybin and greater inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin. |
Abstract
Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three hierarchical levels of analysis: (1) subjective experience (phenomenology), (2) neuroimaging and (3) molecular pharmacology. Phenomenologically, medium and high doses of LSD yield significantly higher ratings of visionary restructuralisation than psilocybin on the 5-dimensional Altered States of Consciousness Scale. Our neuroimaging results reveal that, in general, psychedelics significantly strengthen between-network functional connectivity (FC) while significantly diminishing within-network FC. Pharmacologically, LSD induces significantly more inositol phosphate formation at the 5-HT2A receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT2A, 5-HT2C, or D2 receptors, relative to the 5-HT1A receptor. Our meta-analyses link DMT, LSD, and psilocybin to specific neural fingerprints at each level of analysis. The results show a highly non-linear relationship between these fingerprints. Overall, our analysis highlighted the high heterogeneity and risk of bias in the literature. This suggests an urgent need for standardising experimental procedures and analysis techniques, as well as for more research on the emergence between different levels of psychedelic effects.
Comparable studies
Other systematic reviews and meta-analyses on philosophy of mind, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The brain in flow: A systematic review on the neural basis of the flow state. Participants in studies measuring or manipulating flow state with brain activity recording | 2022 | Systematic review | n = 471 |
| Evidence synthesis indicates contentless experiences in meditation are neither truly contentless nor identical Expert texts from Shamatha, Transcendental, and Stillness Meditation traditions | 2022 | Systematic review | n = 135 |
| Novel psychoactive substances (NPS) use in severe mental illness (SMI) patients: Potential changes in the phenomenology of psychiatric diseases Patients with severe mental illness (SMI), such as psychotic patients | 2017 | Systematic review | |
| Scoping review on shamanistic trances practices. | 2024 | Systematic review | |
| Why is it hard to assess thought disorder? Clarifying the third domain of psychosis. Individuals with psychosis | 2026 | Systematic review |
Citations in the library
Cited by 18
- Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience. Communications Biology April 18, 2025
- The science of psychedelic medicine. Nature Medicine February 6, 2026
- Psychedelic medicine: mechanisms, evidence, and translation to practice BMJ February 23, 2026
- Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HT2A receptor psychedelics from a transdiagnostic perspective. Acta Neuropsychiatrica July 25, 2025
- Stepping back into life: How Psychedelic Assisted Psychotherapy transforms the way of life of the terminally ill General Hospital Psychiatry December 10, 2025
and 13 more in the library
Cites 96
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
and 91 more in the library