A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics
Neil K. Savalia, Ling-Xiao Shao, Alex C. Kwan
Trends in Neurosciences December 21, 2020 DOI: 10.1016/j.tins.2020.11.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Neuroplasticity Psilocybin Serotonin Esketamine Ketamine |
| Keywords | Antidepressant Psychotomimetic Synapse Biological neural network Hallucinogen Nmda receptor Hippocampus |
| Citations | 110 |
| Key points | Proposes that the actions of ketamine and serotonergic psychedelics may converge at dendrites to both enhance and suppress membrane excitability. |
Abstract
Pilot studies have hinted that serotonergic psychedelics such as psilocybin may relieve depression, and could possibly do so by promoting neural plasticity. Intriguingly, another psychotomimetic compound, ketamine, is a fast-acting antidepressant and induces synapse formation. The similarities in behavioral and neural effects have been puzzling because the compounds target distinct molecular receptors in the brain. In this opinion article, we develop a conceptual framework that suggests the actions of ketamine and serotonergic psychedelics may converge at the dendrites, to both enhance and suppress membrane excitability. We speculate that mismatches in the opposing actions on dendritic excitability may relate to these compounds' cell-type and region selectivity, their moderate range of effects and toxicity, and their plasticity-promoting capacities.
Comparable studies
Other theoretical and historical papers on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. | 2014 | Historical analysis | |
| Neuroscience and the Near-Death Experience: Roles for the NMSA-PCP receptor, the sigma receptor and the endopsychosins | 1990 | Theoretical or philosophical paper | |
| A unified model of ketamine's dissociative and psychedelic properties. | 2022 | Theoretical or philosophical paper | |
| An Integrative Approach to Ketamine Therapy May Enhance Multiple Dimensions of Efficacy: Improving Therapeutic Outcomes With Treatment Resistant Depression. | 2021 | Theoretical or philosophical paper | |
| Arketamine for cognitive impairment in psychiatric disorders | 2023 | Theoretical or philosophical paper |
Citations in the library
Cited by 77
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics Frontiers in Psychiatry September 10, 2021
- Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics TIPS - Trends in Pharmacological Sciences September 24, 2021
and 72 more in the library
Cites 43
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- 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
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
and 38 more in the library