Interaction of hallucinogenic rapid-acting antidepressants with mGlu2/3 receptor ligands as a window for more effective therapies.
Barbara Chruścicka-Smaga, Agata Machaczka, Bernadeta Szewczyk, Andrzej Pilc
Pharmacological Reports December 1, 2023 DOI: 10.1007/s43440-023-00547-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression |
| Keywords | Co-treatment Glutamatergic system Rapid-acting antidepressants Mglu2/3 receptors Psychedelics hallucinogens Entheogens Mood disorder Neuroscience brain science Neurobiology Neural systems Antidepressants depression medication |
| Citations | 2 |
| Key findings | Combining rapid-acting antidepressants with mGlu2/3 receptor antagonists may alleviate adverse effects while improving therapeutic outcomes. |
Abstract
The desire to find a gold-standard therapy for depression is still ongoing. Developing one universal and effective pharmacotherapy remains troublesome due to the high complexity and variety of symptoms. Over the last decades, the understanding of the mechanism of pathophysiology of depression and its key consequences for brain functioning have undergone significant changes, referring to the monoaminergic theory of the disease. After the breakthrough discovery of ketamine, research began to focus on the modulation of glutamatergic transmission as a new pharmacological target. Glutamate is a crucial player in mechanisms of a novel class of antidepressants, including hallucinogens such as ketamine. The role of glutamatergic transmission is also suggested in the antidepressant (AD) action of scopolamine and psilocybin. Despite fast, robust, and sustained AD action hallucinogens belonging to a group of rapid-acting antidepressants (RAA) exert significant undesired effects, which hamper their use in the clinic. Thus, the synergistic action of more than one substance in lower doses instead of monotherapy may alleviate the likelihood of adverse effects while improving therapeutic outcomes. In this review, we explore AD-like behavioral, synaptic, and molecular action of RAAs such as ketamine, scopolamine, and psilocybin, in combination with mGlu2/3 receptor antagonists.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cites 33
- 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
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 28 more in the library