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Michael Michaelides

8 papers in the library · 498 citations · publishing 2014-2025

Papers

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Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?

American Journal of Psychiatry March 1, 2025 Marjorie R. Levinstein, Reece C Budinich, Jordi Bonaventura et al. 49 citations

Ketamine is a racemic compound and medication comprised of (S)-ketamine and (R)-ketamine enantiomers and its metabolites. It has been used for decades as a dissociative anesthetic, analgesic, and recreational drug. More recently, ketamine, its enantiomers, and its metabolites have been used or are being investigated for the treatment of refractory depression, as well as for comorbid disorders...

DOI: 10.1176/appi.ajp.20240378 (opens in new tab) Full text (opens in new tab) Ketamine/esketamine #ketamine esketamine Ketalar Special k +4

The dopaminergic effects of esketamine are mediated by a dual mechanism involving glutamate and opioid receptors.

Molecular Psychiatry February 19, 2025 Arianna Rizzo, Maria Zelai Garçon-Poca, Amelie Essmann et al. 14 citations

Esketamine represents a new class of drugs for treating mood disorders. Unlike traditional monoaminergic-based therapies, esketamine primarily targets N-methyl-D-aspartate receptors (NMDAR). However, esketamine is a complex drug with low affinity for NMDAR and can also bind to other targets, such as opioid receptors. Its precise mechanism of action for its antidepressant properties remains...

DOI: 10.1038/s41380-025-02931-3 (opens in new tab) Full text (opens in new tab) Psychopharmacology Depression treatment Brain chemistry Mental health

Sex dependence of opioid-mediated responses to subanesthetic ketamine in rats

Nature Communications January 30, 2024 Tommaso Di Ianni, Sedona N. Ewbank, Marjorie R. Levinstein et al.

Subanesthetic ketamine is increasingly used for the treatment of varied psychiatric conditions, both on- and off-label. While it is commonly classified as an N -methyl D-aspartate receptor (NMDAR) antagonist, our picture of ketamine’s mechanistic underpinnings is incomplete. Recent clinical evidence has indicated, controversially, that a component of the efficacy of subanesthetic ketamine may...

Sex dependence of opioid-mediated responses to subanesthetic ketamine

bioRxiv Preprint Server September 6, 2022 Tommaso Di Ianni, Matine M. Azadian, Sedona N. Ewbank et al. 2 citations preprint

Subanesthetic ketamine rapidly and robustly reduces depressive symptoms in patients with treatment-resistant depression. While it is commonly classified as an N-methyl D-aspartate receptor (NMDAR) antagonist, our picture of ketamine’s mechanistic underpinnings is incomplete. Recent clinical evidence has indicated, controversially, that a component of the efficacy of ketamine in depression may...

DOI: 10.1101/2022.09.06.506854 (opens in new tab) Full text (opens in new tab) Esketamine Rapid-acting antidepressant Sex differences Gender differences +17

Mechanisms of Ketamine and its Metabolites as Antidepressants

Biochemical Pharmacology December 1, 2021 E. Hess, L. Riggs, Michael Michaelides et al. 167 citations

Treating major depression is a medical need that remains unmet by monoaminergic therapeutic strategies that commonly fail to achieve symptom remission. A breakthrough in the treatment of depression was the discovery that the anesthetic (R,S)-ketamine (ketamine), when administered at sub-anesthetic doses, elicits rapid (sometimes within hours) antidepressant effects in humans that are otherwise...

Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability

Molecular Psychiatry April 15, 2021 Jordi Bonaventura, Sherry Lam, Meghan L. Carlton et al. 266 citations

Ketamine, a racemic mixture of (S)-ketamine and (R)-ketamine enantiomers, has been used as an anesthetic, analgesic and more recently, as an antidepressant. However, ketamine has known abuse liability (the tendency of a drug to be used in non-medical situations due to its psychoactive effects), which raises concerns for its therapeutic use. (S)-ketamine was recently approved by the United...

Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal.

Neurotoxicology and Teratology 2016 Lindsay Silva, Rita Black, Michael Michaelides et al.

Adolescents who use marijuana are more likely to exhibit anxiety, depression, and other mood disorders, including psychotic-like symptoms. Additionally, the age at onset of use and the stress history of the individual can affect responses to cannabis. To examine the effect of early life experience on adolescent Δ-9-tetrahydrocannabinol (THC) exposure, we exposed adolescent (postnatal day (P)...

DOI: 10.1016/j.ntt.2016.02.005 (opens in new tab) Full text (opens in new tab) Cb1 receptor expression Corticosterone Delta-9-tetrahydrocannabinol Emotionality +2

Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation.

Neuropsychopharmacology May 2014 Henrietta Szutorisz, Jennifer A DiNieri, Eric Sweet et al.

Recent attention has been focused on the long-term impact of cannabis exposure, for which experimental animal studies have validated causal relationships between neurobiological and behavioral alterations during the individual's lifetime. Here, we show that adolescent exposure to Δ(9)-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, results in behavioral and...