Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications
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 psychedelic...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/1/130 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587737714130944 |
|---|---|
| author | Alice Melani Marco Bonaso Letizia Biso Benedetta Zucchini Ciro Conversano Marco Scarselli |
| author_facet | Alice Melani Marco Bonaso Letizia Biso Benedetta Zucchini Ciro Conversano Marco Scarselli |
| author_sort | Alice Melani |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c5cd04f60d7d431e84bdcfb853b3ada0 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-c5cd04f60d7d431e84bdcfb853b3ada02025-01-24T13:45:30ZengMDPI AGPharmaceuticals1424-82472025-01-0118113010.3390/ph18010130Uncovering Psychedelics: From Neural Circuits to Therapeutic ApplicationsAlice Melani0Marco Bonaso1Letizia Biso2Benedetta Zucchini3Ciro Conversano4Marco Scarselli5Department of Biology, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Surgical and Medical Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Surgical and Medical Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Surgical and Medical Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Surgical, Medical and Molecular Pathology, and Critical Care Medicine, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Surgical and Medical Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyPsychedelics, 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.https://www.mdpi.com/1424-8247/18/1/130psychedelicsDMNCSTCREBUSpsilocybinMDMA |
| spellingShingle | Alice Melani Marco Bonaso Letizia Biso Benedetta Zucchini Ciro Conversano Marco Scarselli Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications Pharmaceuticals psychedelics DMN CSTC REBUS psilocybin MDMA |
| title | Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications |
| title_full | Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications |
| title_fullStr | Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications |
| title_full_unstemmed | Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications |
| title_short | Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications |
| title_sort | uncovering psychedelics from neural circuits to therapeutic applications |
| topic | psychedelics DMN CSTC REBUS psilocybin MDMA |
| url | https://www.mdpi.com/1424-8247/18/1/130 |
| work_keys_str_mv | AT alicemelani uncoveringpsychedelicsfromneuralcircuitstotherapeuticapplications AT marcobonaso uncoveringpsychedelicsfromneuralcircuitstotherapeuticapplications AT letiziabiso uncoveringpsychedelicsfromneuralcircuitstotherapeuticapplications AT benedettazucchini uncoveringpsychedelicsfromneuralcircuitstotherapeuticapplications AT ciroconversano uncoveringpsychedelicsfromneuralcircuitstotherapeuticapplications AT marcoscarselli uncoveringpsychedelicsfromneuralcircuitstotherapeuticapplications |