Some studies have indicated that ketamine has a rapid antidepressant effects, but the underlying molecular mechanism is still unclear. Researchers have found that mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF are related to depression; they elicit opposite effects on cellular functions. It is clear that tissue plasminogen activator (tPA) is a key regulatory element...
Single-dose intravenous (IV) injection of ketamine has shown rapid but transient antidepressant effects. The strategy of repeated-dose ketamine infusions to maintain antidepressant effects has received little systematic study. This study was conducted to examine the efficacy and tolerability of six ketamine infusions in Chinese patients with unipolar and bipolar depression. Ninety seven...
Ketamine is a general anaesthetic with anti-depressant effects at subanaesthetic doses. We hypothesised that intraoperative administration of ketamine would prevent or mitigate postoperative depressive symptoms in surgical patients. We conducted an international, randomised clinical trial testing the effects of intraoperative administration of ketamine [0.5 mg kg-1 (Lo-K) or 1.0 mg kg-1 (Hi-K)]...
This study tested the feasibility, acceptability, and preliminary effects of a mindfulness-based intervention with at-risk adolescents from a predominantly Hispanic/Latino community. Seven adolescents (57% female, 85% Hispanic/Latino) completed the mindfulness-based intervention, demonstrating feasibility, and reported acceptability as well as sustained improvements in depressive symptoms,...
The entropic brain hypothesis proposes that within upper and lower limits, after which consciousness may be lost, the entropy of spontaneous brain activity indexes the informational richness of conscious states. Here the hypothesis is revisited four years on from its original publication. It is shown that the principle that the entropy of brain activity is elevated in the psychedelic state is...
Many children suffer from headaches. Since stress may trigger headaches, effective techniques to cope with stress are needed. We investigated the effectiveness of two mind-body techniques, transcendental meditation (TM) or hypnotherapy (HT), and compared them with progressive muscle relaxation (PMR) exercises (active control group). Children (9-18 years) suffering from primary headaches more...
The symptoms of major depressive disorder (MDD) are rapidly alleviated by administration of a single dose of the glutamatergic modulator ketamine. However, few studies have investigated the potential sustained neural effects of this agent beyond immediate infusion. This study used functional magnetic resonance imaging to examine the effect of a single ketamine infusion on the resting state...
Background: Evidence suggests that classical psychedelics can promote enduring changes in personality, attitudes and optimism, as well as improvements in mental health outcomes. Aim: To investigate the effects of a composite intervention, involving psilocybin, on pessimism biases in patients with treatment-resistant depression (TRD). Methods: Patients with TRD (n = 15) and matched, untreated...
The acute activation of kappa opioid receptors (KOPr) produces antinociceptive and anti-cocaine effects, however, their side-effects have limited further clinical development. Mesyl Sal B is a potent and selective KOPr analogue of Salvinorin A (Sal A), a psychoactive natural product isolated from the plant Salvia divinorum. We assessed the antinociceptive, anti-cocaine, and side-effects of...
Depression is a common mental disorder that is associated with memory dysfunction. Ketamine has recently been demonstrated to be a rapid antidepressant. The mechanisms underlying how depression induces memory dysfunction and how ketamine relieves depressive symptoms remain poorly understood. In this work, we have three groups of male C57BL/6J mice: mice exposed to chronic social defeat stress...
Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties...
The discovery of the antidepressant effects of ketamine has opened a breakthrough opportunity to develop a truly novel class of safe, effective, and rapid-acting antidepressants (RAADs). In addition, the rapid and robust biological and behavioral effects of ketamine offered a unique opportunity to utilize the drug as a tool to thoroughly investigate the neurobiology of stress and depression in...
Ketamine has been shown to produce a rapid and potent antidepressant response in patients with treatment-resistant depression. Currently ketamine is most commonly administered as a 40-minute intravenous infusion, though it is unknown whether this is the optimal route of administration. To determine the plasma concentration time course of the R- and S-enantiomers of ketamine and norketamine...
Over the past decade, ketamine has been one of the most commonly studied potential antidepressants. This is because it produces a spectacularly rapid and persistent therapeutic effect in people suffering from severe treatment-resistant depression (TRD), for which classical drugs are ineffective. Similar efficacy was demonstrated for scopolamine, a drug belonging to a completely different...
(R,S)-Ketamine produces rapid, robust, and sustained antidepressant effects in major depressive disorder. Specifically, its pharmacological efficacy in treatment refractory depression is considered a major breakthrough in the field. However, the mechanism of action of ketamine's rapid effect remains to be determined. In order to identify pathways that are responsible for ketamine's effect, a...
Depression is one of the most common psychiatric issues with a proportion of adults with major depressive disorder who fail to achieve remission with index pharmacological treatment. There are unmet needs in ADT focus on non-monoaminergic agents. Accumulating evidence suggests that the N-Methyl-d-aspartate receptor (NMDAR) plays an important role in the neurobiology and treatment of major...
Intravenous ketamine has been established as an efficacious and safe treatment, with transient effect, for treatment-resistant depression. However, the effectiveness of intravenous ketamine in non-research settings and with ultraresistant depression patients remains understudied. This study aims to measure the response and remission rates in ultraresistant depression patients in a clinical...
Evidence links depression and stress to more rapid progression of HIV-1 disease. We conducted a randomized controlled trial to test whether an intervention aimed at improving stress management and emotion regulation, mindfulness-based stress reduction (MBSR), would improve immunological (i.e. CD4+ T-cell counts) and psychological outcomes in persons with HIV-1 infection. We randomly assigned...
Treatment-resistant depression (TRD) is a disabling and demoralizing phenomenon for patients and clinicians. For many years, treatment for depression has relied on the monoamine theory, with medications limited in efficacy and requiring prolonged use before any therapeutic effects are evident. The current article reviews novel approaches to pharmacological treatment of TRD, including...
BACKGROUND: Ketamine has proven to have rapid, robust antidepressant effects on treatment-resistant depression. However, whether repeated ketamine infusions would cause short-and long-term neurocognitive impairments was not clear. Our aims were to investigate the neurocognitive effects of six ketamine infusions and to examine the association between these infusions and the antidepressant...