Research published in European Journal of Pharmacology

Psilocybin-associated microRNA changes in the pig brain: Establishing an nCounter pipeline for cross-species microRNA quantification.

European Journal of Pharmacology August 1, 2026 Erik Kaadt, Rolf Søkilde, Hanne Demant Garling et al.

Novel treatment strategies are needed to address treatment resistance and delayed onset of action in psychiatry. Psilocybin has shown promise as a treatment for major depressive disorder, but the molecular changes associated with its effects remain incompletely understood. In parallel, microRNAs (miRNAs) have been implicated in depression and in responses to antidepressant interventions. Here,...

DOI: 10.1016/j.ejphar.2026.179222 Full text

Intranasal Ketamine Alleviates Depressive-like Behaviors in Chronic Unpredictable Mild Stress Rats in Association with Hypothalamic NADH:Ubiquinone Oxidoreductase Subunit A10.

European Journal of Pharmacology July 19, 2026 Yongning Lv, Zihe Yang, Linjie Li et al.

Intranasal ketamine represents a rapid and minimally invasive antidepressant strategy, yet the molecular mechanisms underlying its antidepressant-like effects after intranasal administration remain incompletely understood. Male Sprague-Dawley rats were subjected to a 28-day chronic unpredictable mild stress (CUMS) paradigm and then received intranasal racemic ketamine at 8.58 mg/kg twice weekly...

DOI: 10.1016/j.ejphar.2026.179153 Full text Cums Hypothalamus Intranasal ketamine Mitochondrial complex i +2

Antidepressant effect of psychedelic compounds and mechanisms underlying the G protein-coupled receptors activation psychedelics: Antidepressant action and GPCR signaling.

European Journal of Pharmacology July 10, 2026 Amanda Gollo Bertollo, Vinicius Alexandre Wippel, Maiqueli Eduarda Dama Mingoti et al.

Major Depressive Disorder (MDD) is a debilitating mental health condition that significantly impacts quality of life. Despite available pharmacological treatments, response rates remain suboptimal, with a considerable number of patients experiencing treatment-resistant depression (TRD). Indeed, classical antidepressants, primarily targeting monoaminergic systems, exhibit a therapeutic delay due...

DOI: 10.1016/j.ejphar.2026.179036 Full text 5-ht2a receptor Antidepressant action G protein-coupled receptors Psychedelic compounds

Perinatal LC-ω-3-PUFA supplementation offsets prenatal THC-induced cognitive deficit via sex-specific modulation of hippocampal neuroplasticity.

European Journal of Pharmacology June 1, 2026 Gianluca Lavanco, Valentina Castelli, Cesare D'Amico et al.

Long-chain polyunsaturated fatty acids (LC-PUFAs) are crucial for brain development, with ω-3 species supporting neuronal membrane architecture, synaptogenesis and cognitive maturation, and ω-6 species linking lipid metabolism to neuronal signalling via the endocannabinoid system (ECS), the network of receptors, lipid mediators, and enzymatic pathways that orchestrate neurodevelopmental...

DOI: 10.1016/j.ejphar.2026.179064 Full text Endocannabinoid system Excitatory/inhibitory balance Hippocampal memory Lc-ω-3-pufas +1

Distinguishing psychomimetic from antidepressant-like effects in mice using molecular and electrophysiological biomarkers.

European Journal of Pharmacology May 1, 2026 Esteban Merino, A. Cervera-Ferri, Enrique Lanuza et al.

Ketamine exerts rapid, long-lasting antidepressant effects after a single administration and thus overcomes the limitations of classic drugs, but also induces psychomimetic effects. It is, therefore, essential to delve deeper into its mechanisms of action to optimize its use as an antidepressant. With this aim, we examined, in male mice, the temporal evolution of the antidepressant-like and...

DOI: 10.1016/j.ejphar.2026.178994 Full text

L-type voltage-dependent calcium channels in the ventromedial orbitofrontal and prefrontal cortices mediate the inhibitory effects of (S)-ketamine but not (R)-ketamine on marble burying in male mice

European Journal of Pharmacology October 25, 2025 Satoshi Deyama, Kenji Mishiro, Munetaka Kunishima et al.

Glutamatergic abnormalities in several brain regions, including the ventromedial orbitofrontal cortex (vmOFC) and prefrontal cortex (vmPFC), have been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). (R, S)-ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and enantiopure (S)-ketamine may have therapeutic effects in patients and animal models of OCD....

DOI: 10.1016/j.ejphar.2025.178301

2,5-dimethoxy-4-methylamphetamine (DOM)-induced Gait Alterations in Mice: Dissecting the Role of 5-HT2A/2C Receptor-mediated Mechanisms.

European Journal of Pharmacology September 15, 2025 Bin Li, Shanshan Jiang, Yi-shan Yao et al.

Psychedelics have demonstrated significant therapeutic potential in treating various psychiatric disorders; however, their effects on motor function remain poorly understood. This study investigated the impact of 2,5-dimethoxy-4-methylamphetamine (DOM), a classical phenethylamine psychedelic agent, on gait parameters in C57BL/6J mice using an active gait monitoring system. We found that 0.3-3...

DOI: 10.1016/j.ejphar.2025.178170

Preincubation with antipsychotic drugs protects against in vitro phencyclidine-mediated spontaneous neuronal network suppression.

European Journal of Pharmacology September 5, 2025 Timo Jendrik Faustmann, Stephan Theiss, Philipp Görtz et al. 1 citation

Phencyclidine (PCP), a non-competitive N-methyl-D-aspartate receptor antagonist, is known to produce schizophrenia-like psychosis in humans, including positive and negative symptoms as well as cognitive dysfunction. Moreover, acute administration of PCP can emulate corresponding behavioral symptoms in rodents. We investigated the effect of PCP and the possible protective potential of typical...

DOI: 10.1016/j.ejphar.2025.177810 Full text Antipsychotic drugs Microelectrode array Phencyclidine Schizophrenia

Role of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and psychedelics in the treatment of major depressive disorder: A perspective on mechanistic insight and current status.

European Journal of Pharmacology August 15, 2025 Niharika Singh, Puja Panwar Hazari, Parul Mittal et al. 16 citations

Globally, depression affects millions of people of all ages, making it one of the significant contributors to deteriorating quality of life by causing neurological impairments that eventually weaken cognition, learning, and memory. According to the monoamine hypothesis, depression is associated with decreased serotonin, dopamine, and norepinephrine levels in the central nervous system. Drugs...

DOI: 10.1016/j.ejphar.2025.177737 Full text Depression Serotonin-norepinephrine reuptake inhibitors Antidepressants ssris Snris +6

The antidepressant potential of (2R,6R)-hydroxynorketamine: A detailed review of pre-clinical findings.

European Journal of Pharmacology July 15, 2025 Isis Koutrouli, Kristýna Mazochová, Rachel R. Horsley 4 citations

Depression affects hundreds of millions globally, and in 2019, esketamine, an S-enantiomer of ketamine, was approved for treatment-resistant depression (TRD). While effective, esketamine carries risks, including abuse potential and adverse effects even at low doses. As a result, ketamine's metabolite, (2R,6R)-hydroxynorketamine ((2R,6R)-HNK), has garnered attention for its potential...

DOI: 10.1016/j.ejphar.2025.177604 Full text Behavioral despair Hydroxynorketamine Learned helplessness Pre-clinical +5

Plasma esketamine and noresketamine levels and antidepressant response with oral esketamine treatment.

European Journal of Pharmacology July 5, 2025 Jolien K E Veraart, Sanne Y Smith-Apeldoorn, Jeanine Kamphuis et al. 2 citations

Oral esketamine has relatively low and variable bioavailability, which may complicate broader use as an antidepressant. This study aimed to investigate associations between different pharmacokinetic outcomes and change in depressive symptoms following oral esketamine administration in patients with treatment-resistant depression. Understanding such associations may inform dosing and...

DOI: 10.1016/j.ejphar.2025.177470 Full text Mdd Spravato Clinical depression Esketamine ketamine +5

Pharmaco-toxicological effects of the synthetic cannabinoids 4F-ABUTINACA, SDB-005, and JWH-018 in mice. In vitro and in vivo studies.

European Journal of Pharmacology April 1, 2025 Xuwen Luo, Lixin Kuai, Xuesong Shi et al.

BACKGROUND Synthetic cannabinoids (SCs) are currently one of the most severely abused new psychoactive substances in the world. However, there remains a notable lack of pharmacological data on the newly emerged synthetic cannabinoids. In the present study, the in vitro and in vivo pharmacological effects of the fourth-generation synthetic cannabinoids 4F-ABUTINACA and SDB-005 are determined and...

DOI: 10.1016/j.ejphar.2025.177586

Mice lacking the serotonin transporter do not respond to the behavioural effects of psilocybin.

European Journal of Pharmacology March 15, 2025 James J Gattuso, Carey Wilson, Shanshan Li et al. 16 citations

Psilocybin is a serotonergic psychedelic with therapeutic potential for several neuropsychiatric disorders, including depression and anxiety disorders. Serotonin transporter (5-HTT) knockout mice (KO) are a well-validated mouse model of anxiety/depression and are relevant to both chronic treatment with serotonin transporter reuptake inhibitors (SSRIs) and polymorphisms in the serotonin...

DOI: 10.1016/j.ejphar.2025.177304 Full text Depression Psilocybin Serotonin transporter Psychedelic medicine +5

Repeated intermittent administration of 3,4-methylenedioxymethamphetamine mitigates demyelination in the brain from cuprizone-treated mice.

European Journal of Pharmacology March 15, 2025 Mingming Zhao, Akifumi Eguchi, Rumi Murayama et al. 6 citations

3,4-Methylenedioxymethamphetamine (MDMA), commonly known as a recreational drug, may also offer therapeutic benefits for mental health. Population-based studies suggest that MDMA users have a lower risk of demyelinating diseases, such as depression. Given the role of the gut microbiota in mediating MDMA's effects, we hypothesized that MDMA might confer mental health benefits via the gut-brain...

DOI: 10.1016/j.ejphar.2025.177345 Full text MDMA Demyelination Gut microbiota Metabolites +4

Cognitive and kinematic markers of ketamine effects in behaving non-human primates.

European Journal of Pharmacology January 15, 2025 Pierre Pouget, Pierre Daye, Martin Paré 2 citations

Ketamine is widely used to probe cognitive functions relying on the properties of methyl-D-aspartate receptor (NMDAR) synaptic transmission. Numerous works have proved that cognitive performance and adjustments in the decision or perceptual domains are affected after ketamine injection in general circulation of primates. Here, we take advantage of that in the brain stem; horizontal saccade...

DOI: 10.1016/j.ejphar.2024.177185 Full text Ketamine Cognition Motor kinematic Saccade +4

Transforming growth factor-β1 mediates the beneficial effects of arketamine on demyelination and remyelination in the brains of cuprizone-treated mice.

European Journal of Pharmacology December 15, 2024 Ming-Ming Zhao, Ting-Ting Zhu, Dan Xu et al. 14 citations

The novel antidepressant arketamine, the (R)-enantiomer of ketamine, has been shown to ameliorate demyelination and facilitate remyelination in the brains of cuprizone (CPZ)-treated mice. However, the mechanisms behind its effects remain unclear. Given the role of transforming growth factor β1 (TGF-β1) in arketamine's antidepressant-like effects, we examined whether TGF-β1 also plays a role in...

DOI: 10.1016/j.ejphar.2024.177096 Full text Arketamine Cuprizone Demyelination Remyelination +5

Esketamine improves cognitive function in sepsis-associated encephalopathy by inhibiting microglia-mediated neuroinflammation.

European Journal of Pharmacology November 15, 2024 Hui Li, Wen Hu, Zhen Wu et al. 11 citations

Microglia-mediated neuroinflammation is critical in the pathogenesis of sepsis-associated encephalopathy(SAE). Identifying the key factors that inhibit microglia-mediated neuroinflammation holds promise as a potential target for preventing and treating SAE. Esketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been proposed to possess protective and therapeutic...

DOI: 10.1016/j.ejphar.2024.177014 Full text Spravato Bdnf Microglia Sepsis-associated encephalopathy +5

Combining brief recall and ketamine treatment prevents stress-primed methamphetamine memory reinstatement via heightening mPFC GABA activity.

European Journal of Pharmacology June 5, 2024 Li-Han Sun, Lung Yu, Ya-Hsuan Chan et al. 2 citations

This study aimed to assess whether brief recall of methamphetamine (MA) memory, when combined with ketamine (KE) treatment, may prevent stress-primed MA memory reinstatement. Combining 3-min recall and KE facilitated MA memory extinction and resistance to subsequent stress-primed reinstatement. Such combination also produced glutamate metabotropic receptor 5 (mGluR5) upregulation in animals'...

DOI: 10.1016/j.ejphar.2024.176559 Full text Methamphetamine Reconsolidation Reinstatement Addiction treatment +4

Effects of nitrous oxide and ketamine on electrophysiological and molecular responses in the prefrontal cortex of mice: A comparative study.

European Journal of Pharmacology April 5, 2024 Stanislav Rozov, Roosa Saarreharju, Stanislav Khirug et al.

Nitrous oxide (N2O; laughing gas) has recently reported to produce rapid antidepressant effects, but little is known about the underlying mechanisms. We performed transcriptomics, in situ hybridization, and electrophysiological studies to examine the potential shared signatures induced by 1 h inhalation of 50% N2O and a single subanesthetic dose of ketamine (10 mg/kg, i.p.) in the medial...

DOI: 10.1016/j.ejphar.2024.176426 Full text Ketamine Medial prefrontal cortex Nitrous oxide Single-unit activity

The novel non-hallucinogenic compound DM506 (3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole) induces sedative- and anxiolytic-like activity in mice by a mechanism involving 5-HT2A receptor activation.

European Journal of Pharmacology March 5, 2024 Hugo R Arias, Deborah Rudin, Dustin J Hines et al. 12 citations

The anxiolytic and sedative-like effects of 3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (DM506), a non-hallucinogenic compound derived from ibogamine, were studied in mice. The behavioral effects were examined using Elevated O-maze and novelty suppressed feeding (NSFT) tests, open field test, and loss of righting reflex (LORR) test. The results showed that 15 mg/kg DM506 induced acute...

DOI: 10.1016/j.ejphar.2024.176329 Full text 5-ht2a/2b receptors Anxiolytic activity Ibogaminalog Molecular docking +1

Psychoactive substances 25H-NBOMe and 25H-NBOH induce antidepressant-like behavior in male rats.

European Journal of Pharmacology September 15, 2023 Barbara G Ferri, Cintia O De Novais, Raquel S Bonani et al. 11 citations

Ring-substituted phenethylamines are believed to induce psychedelic effects primarily by interacting with 5-hydroxytryptamine 2 (5-HT2A) receptors in the brain. We assessed the effect of the psychedelic substances 25H-NBOMe and 25H-NBOH on the depressive-like behavior of male adult rats. Naive Wistar rats were divided into groups to assess the effects of different doses (0.1 mg/kg, 1 mg/kg, and...

DOI: 10.1016/j.ejphar.2023.175926 Full text Depression Forced swimming test Psychedelics

Influence of adrenalectomy on the gut microbiome and MDMA-induced hyperthermia.

European Journal of Pharmacology April 15, 2023 Amal Aburahma, Srishti Rana, Ray A. Larsen et al. 5 citations

The increased use of the stimulant drug, 3,4-methylenedioxymethamphetamine (MDMA), more commonly known as Ecstasy, Molly or X, has been linked to the development of life-threatening hyperthermia in human and animal models. The current study aimed to investigate the role of the gut-adrenal axis in MDMA-induced hyperthermia by assessing the influence of the acute exogenous supplementation with...

DOI: 10.1016/j.ejphar.2023.175643 Full text

S-ketamine exerts sex- and dose-dependent anti-compulsive-like effect as monotherapy or in augmentation to fluoxetine.

European Journal of Pharmacology November 1, 2022 Júlia Grigorini Mori Ayub, C. Tosta, Breno Lopes Macedo et al.

Since a significant body of studies supports the involvement of glutamatergic neurotransmission in the neurobiology of obsessive-compulsive disorder (OCD). Ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist with rapid and sustained antidepressant effect, raises as a potential new anti-OCD drug. Evidence from pre-clinical studies indicates that female mice are more sensitive...

DOI: 10.1016/j.ejphar.2022.175382

Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms.

European Journal of Pharmacology May 7, 2021 D. Fonseca, D. M. Ribeiro, Margarida Tapadas et al. 23 citations

3,4-methylenedioxymethamphetamine or MDMA (known as "ecstasy") is a recreational drug of abuse, popular worldwide for its distinctive psychotropic effects. Currently, the therapeutic potential of MDMA in psychotherapy has attracted a lot of interest from the scientific community, despite the multitude of effects that this drug of abuse elicits on the human body. While neuronal effects have been...

DOI: 10.1016/j.ejphar.2021.174156

Pharmacological characterizations of the 'legal high' fluorolintane and isomers.

European Journal of Pharmacology August 15, 2019 Jason Wallach, Tristan Colestock, Julià Agramunt et al.

1,2-Diarylethylamines represent a class of molecules that have shown potential in the treatment of pain, epilepsy, neurodegenerative disease and depression. Examples include lefetamine, remacemide, and lanicemine. Recently, several 1,2-diarylethylamines including the dissociatives diphenidine, methoxphenidine and ephenidine as well as the opioid MT-45, have appeared as 'research chemicals' or...

DOI: 10.1016/j.ejphar.2019.172427 Full text Ketamine Diphenidine Fluorolintane Legal high +1

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