The empathogen 3,4-methylenedioxymethamphetamine (MDMA) is the prototypical prosocial club drug inducing emotional openness to others. It has recently been shown that acutely applied 3,4-MDMA in fact enhances emotional empathy and prosocial behavior, while it simultaneously decreases cognitive empathy. However, the long-term effects of 3,4-MDMA use on socio-cognitive functions and social...
Abstract Background Modulation of glutamatergic synaptic transmission by N-methyl-D-aspartate receptors can produce rapid and sustained antidepressant effects. Rapastinel (GLYX-13), initially described as a N-methyl-D-aspartate receptor partial glycine site agonist, exhibits rapid antidepressant effect in rodents without the accompanying dissociative effects of N-methyl-D-aspartate receptor...
Background: Macrophage migration inhibitory factor is a proinflammatory cytokine that has been associated with various psychiatric disorders. MicroRNA-451a can directly target macrophage migration inhibitory factor and downregulate its expression in cells. However, the role of macrophage migration inhibitory factor and microRNA-451a in psychiatric patients treated with psychotherapeutic...
Major depressive disorder (MDD) affects approximately 10% to 20% of the US population (Kessler et al. , 2005); thus, the economic burden of MDD is immense. Currently, selective serotonin reuptake inhibitors and serotonin- and noradrenaline-reuptake inhibitors are widely prescribed for patients with MDD as first-line treatments. However, these medications have several drawbacks; approximately...
Abstract Background We previously reported that serotonergic transmission plays an important role in antidepressant effects of ketamine. However, detailed mechanisms have not been elucidated. Among the serotonin receptor subtypes, the serotonin1A receptor in the medial prefrontal cortex has an important role in depression. Here, we investigated the role of the medial prefrontal cortex...
Background: Stimulants such as methylphenidate and modafinil are frequently used as cognitive enhancers in healthy people, whereas 3,4-methylenedioxymethamphetamine (ecstasy) is proposed to enhance mood and empathy in healthy subjects. However, comparative data on the effects of methylphenidate and modafinil on negative emotions in healthy subjects have been partially missing. The aim of this...
Background: Previous reports suggest that 5-hydroxytryptamine might play a role in the antidepressant actions of (R,S)-ketamine. However, its role in the antidepressant actions of (R)-ketamine, which is more potent than (S)-ketamine, is unknown. This study was conducted to examine whether 5-hydroxytryptamine depletion affects the antidepressant actions of (R)-ketamine in a chronic social defeat...
Background: (R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the...
Background: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset...
Background: Like other complex psychosocial interventions, mindfulness-based treatments comprise various modality-specific components as well as nonspecific therapeutic ingredients that collectively contribute to efficacy. Consequently, the isolated effects of mindfulness strategies per se remain unclear. Methods: Using a randomized double-blind design, we compared the isolated effects of...
Background: Impaired empathic abilities lead to severe negative social consequences and influence the development and treatment of several psychiatric disorders. Furthermore, empathy has been shown to play a crucial role in moral and prosocial behavior. Although the serotonin system has been implicated in modulating empathy and moral behavior, the relative contribution of the various serotonin...
Background: Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and...
Background: Psychostimulants such as methylphenidate and modafinil are increasingly used by healthy people for cognitive enhancement purposes, whereas the acute effect of 3,4-methylenedioxymethamphetamine (ecstasy) on cognitive functioning in healthy subjects remains unclear. This study directly compared the acute effects of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine on...
Healthy people with a family history of alcohol problems show a pattern of subjective responses to alcohol that resemble those of affected probands. Studies on ketamine suggest that up-regulation of N-methyl-D-aspartate receptors (NMDARs) underlies these effects, and point to a pharmacologically-responsive endophenotype reflecting enhanced risk for alcohol-use disorders. Subjective stimulant...
Functional neurological disorders are frequently encountered in clinical practice. They have a poor prognosis and treatment options are limited. Their etiology is unknown, but leading theories propose a disturbance of somatic self-representation: the mind perceives dysfunction of a body region despite intact motor and sensory pathways. Central to this model is the concept of an abnormal...
Background: The neurovascular plasticity of hippocampus is an important theory underlying major depression. Ketamine as a novel glutamatergic antidepressant drug can induce a rapid antidepressant effect within hours. In a mechanistic proof of this concept, we examined whether ketamine leads to an increase in synaptogenesis and vascularization within 24 hours after a single injection in a...
Dysfunction of dopaminergic, GABAergic, and glutamatergic function underlies many core symptoms of schizophrenia. Combined neonatal injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP), and post-weaning social isolation of rats produces a behavioral syndrome with translational relevance to several core symptoms of schizophrenia. This study uses DNA microarray to...
Background: Similar to the N-methyl-D-aspartate receptor antagonist ketamine, the metabotropic glutamate 2/3 receptor antagonist, MGS0039, shows antidepressant effects. However, there are no reports comparing these 2 compounds in the social defeat stress model of depression. Methods: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible...
Objective: Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus than the general population, and even first-episode, drug-naive (FEDN) patients with schizophrenia have shown a higher prevalence of impaired glucose tolerance (IGT) than the general population.We aimed to investigate the prevalence of abnormal glucose tolerance after glucose loading, and to examine the...
Psilocybin, a classical tryptamine hallucinogen, serves as a model of acute psychosis in humans.Intoxication with this compound induces significant alterations in perception, thought disturbance and emotional processing, effects that mimic psychotic symptoms.The neurochemical basis of its effects is related to the stimulation of serotonin 5-HT 1A a 5-HT 2A/C receptors.Disconnection is one of...
Background: Esketamine and ketamine have been shown to produce rapid antidepressant action in patients with treatmentresistant depression (TRD).The aim of the current study was to assess the efficacy, safety and dose response of intranasal esketamine in patients with TRD.Methods: This was a 2-Panel, doubly-randomized, double-blind, placebo-controlled, multicenter study.Panel A was conducted in...
Psilocybin, a classical tryptamine hallucinogen, serves as a model of acute psychosis in humans.Intoxication with this compound induces significant alterations in perception, thought disturbance and emotional processing, effects that mimic psychotic symptoms.The neurochemical basis of its effects is related to the stimulation of serotonin 5-HT 1A a 5-HT 2A/C receptors.Disconnection is one of...
Background: Esketamine and ketamine have been shown to produce rapid antidepressant action in patients with treatmentresistant depression (TRD). The aim of the current study was to assess the efficacy, safety and dose response of intranasal esketamine in patients with TRD. Methods: This was a 2-Panel, doubly-randomized, double-blind, placebo-controlled, multicenter study. Panel A was conducted...
Specific objective of the study: This study is aimed to investigate desipramine, venlafaxine and bupropion on depression and anxiety in mice. Methods used: We used a classic tricyclic antidepressant, desipramine; a serotonin-norepinephrine reuptake inhibitör, venlafaxine; a second-generation antidepressant agent that blocks centrally the reuptake of noradrenaline and dopamine, bupropion in...
Abstract Objective: One third of major depressive disorder (MDD) patients are unresponsive to antidepressant drugs, a sub-type known as treatment resistant depression (TRD). Acute intravenous administration of ketamine at sub-anaesthetic dosage is the only efficacious pharmacological treatment in TRD. Development of TRD preclinical assays to screen for more efficacious antidepressant drugs and...