Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics
Cato M. H. de Vos, Natasha L. Mason, Kim P. C. Kuypers
Frontiers in Psychiatry September 10, 2021 DOI: 10.3389/fpsyt.2021.724606 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Systematic review of 20 studies (16 preclinical, 4 clinical) |
| Interventions | Ayahuasca DMT psilocybin LSD |
| Topics | Neuroplasticity |
| Keywords | Antidepressant Anxiolytic Cognition |
| Citations | 259 |
| Key findings | Psychedelics induce rapid and lasting molecular and cellular neuroplasticity changes that parallel their clinical effects in stress-related disorders. |
Abstract
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies ( n = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.
Comparable studies
Other systematic reviews and meta-analyses on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neurobiological Changes Induced by Mindfulness and Meditation: A Systematic Review. | 2024 | Systematic review | |
| Mindfulness-Based Cognitive Therapy in Clinical Practice: A Systematic Review of Neurocognitive Outcomes and Applications for Mental Health and Well-Being. | 2025 | Systematic review | |
| Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications. | 2025 | Systematic review | |
| Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD. | 2025 | Systematic review | |
| Effects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review. | 2024 | Systematic review |
Citations in the library
Cited by 219
- Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review Frontiers in Psychiatry July 12, 2022
- Psychedelic-Assisted Psychotherapy—A Systematic Review of Associated Psychological Interventions Frontiers in Psychology June 10, 2022
- Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Journal of Affective Disorders February 1, 2023
- A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Cell Reports March 28, 2023
- Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants. Neuropsychopharmacology October 1, 2023
and 214 more in the library
Cites 55
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology December 1, 2011
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
- The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. ACS Pharmacology & Translational Science December 10, 2020
and 50 more in the library