Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications
Marco Bonaso, Letizia Biso, Benedetta Zucchini, Ciro Conversano, Marco Scarselli, Alberto Melani
Pharmaceuticals January 19, 2025 DOI: 10.3390/ph18010130 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | MDMA psilocybin LSD |
| Topics | Default mode network MDMA Psilocybin |
| Keywords | Consciousness Persistent vegetative state Cognition Hallucinogen |
| Citations | 13 |
| Key findings | Psychedelics enhance functional connectivity between sensory brain areas while reducing connectivity in associative areas, decreasing neural rigidity and increasing plasticity, which underlies their therapeutic efficacy in treatment-resistant psychiatric conditions. |
Abstract
Psychedelics, historically celebrated for their cultural and spiritual significance, have emerged as potential breakthrough therapeutic agents due to their profound effects on consciousness, emotional processing, mood, and neural plasticity. This review explores the mechanisms underlying psychedelics’ effects, focusing on their ability to modulate brain connectivity and neural circuit activity, including the default mode network (DMN), cortico-striatal thalamo-cortical (CSTC) loops, and the relaxed beliefs under psychedelics (REBUS) model. Advanced neuroimaging techniques reveal psychedelics’ capacity to enhance functional connectivity between sensory cerebral areas while reducing the connections between associative brain areas, decreasing the rigidity and rendering the brain more plastic and susceptible to external changings, offering insights into their therapeutic outcome. The most relevant clinical trials of 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and lysergic acid diethylamide (LSD) demonstrate significant efficacy in treating treatment-resistant psychiatric conditions such as post-traumatic stress disorder (PTSD), depression, and anxiety, with favorable safety profiles. Despite these advancements, critical gaps remain in linking psychedelics’ molecular actions to their clinical efficacy. This review highlights the need for further research to integrate mechanistic insights and optimize psychedelics as tools for both therapy and understanding human cognition.
Comparable studies
Other narrative reviews on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Brain's Default Mode Network | 2015 | Review | |
| Default Mode Network Activity and Connectivity in Psychopathology | 2012 | Review | |
| 20 years of the default mode network: A review and synthesis | 2023 | Review | |
| On the relationship between the “default mode network” and the “social brain” | 2012 | Review | |
| The default mode network and social understanding of others: what do brain connectivity studies tell us Healthy subjects, with some studies on patients with autism and psychopathy | 2014 | Review |
Citations in the library
Cited by 12
- Psychedelics and Eating Disorders: Exploring the Therapeutic Potential for Anorexia Nervosa and Beyond ACS Pharmacology & Translational Science March 7, 2025
- New Agents in the Treatment of Psychiatric Disorders: What Innovations and in What Areas of Psychopathology? Pharmaceuticals April 30, 2025
- Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach. Frontiers in Psychiatry 2025
- Is there a place for psychedelics in sports practice? Acta Neuropsychiatrica 2025
- Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review International Journal of Molecular Sciences September 10, 2026
and 7 more in the library
Cites 59
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
and 54 more in the library