Abstract Background Approximately a third of people with anorexia nervosa (AN) develop a severe and enduring form of the illness, which is often accompanied by depression. This can be a key barrier to recovery. Anti-depressant medications are less effective in treating depression in patients with acute AN, thus new pharmacological treatment options are needed. Ketamine is currently used for...
Setting up a psychedelic study can be a long, arduous, and Kafkaesque process. Researchers are faced with a host of challenges in this rapidly evolving field, necessitating a range of considerations that remain largely unstandardised. Many of the complexities inherent to psychedelic research also challenge existing assumptions around, for example, approaches to psychiatric prescribing, the...
The therapeutic potential of psychedelics is currently being explored in a range of neuropsychiatric conditions. Nevertheless, their designation as Schedule 1 substances causes substantial regulatory and economic barriers to research. Rigorous human mechanistic studies are required to address the critical knowledge gaps surrounding the mechanisms underlying the putative treatment effects of...
Analyses of neuroimaging data increasingly leverage the distribution of neurotransmitter receptors derived from Positron Emission Tomography (PET) to bridge the gap between micro- and macro-scale brain function. However, these receptor maps are highly spatially overlapping which can give rise to interpretive and analytical challenges. Here, we systematically investigate the impact of spatial...
Accumulating evidence suggests that the opioid system may modulate ketamine's rapid antidepressant effects. The objective of this study was to test whether opioid system modulation via naltrexone alters ketamine's acute effects on regional cerebral blood flow (rCBF) in major depressive disorder (MDD), and whether these changes relate to symptom measures and map onto receptor density profiles....
Ketamine has demonstrated rapid antidepressant efficacy in treatment-resistant depression (TRD), but clinical decision-making is challenging due to variability in individual response. Current trial-and-error prescribing practices may expose patients to ineffective treatment and avoidable adverse effects, underscoring the need for reliable predictive tools to optimize treatment selection and...
Psychedelics are gaining attention as putative treatments for a range of psychiatric conditions, and evidence suggests that they produce sustained behavioural and clinical change. Enhanced learning is an emerging candidate mechanism mediating these sustained effects. This narrative review synthesises evidence across behavioural, neural and computational levels to examine the current evidence...
We investigated the potential role of the opioid system in modulating glutamatergic effects of ketamine administration in major depressive disorder. Twenty-six adults with major depressive disorder participated in a double-blind crossover study, receiving oral placebo or 50 mg naltrexone before an intravenous infusion of 0.5 mg per kg ketamine. Brain glutamatergic activity in the anterior...
Introduction: Psychedelics are emerging as potential treatments for neuropsychiatric conditions, with evidence suggesting a single administration can lead to enduring behavioural changes. While the underlying putative mechanism(s) remain unclear, there is evidence supporting altered learning as a key candidate. Aim: This systematic review examined studies assessing the effects of psychedelics...
Ketamine, a rapid-acting N-methyl-D-aspartate receptor antagonist used as a therapeutic for treatment-resistant depression (TRD), is usually administered intravenously or intranasally. This randomized, double-blind, placebo-controlled, Phase 1 study investigated safety and tolerability (primary endpoint), pharmacokinetics (PK) and pharmacodynamics (PD) of an immediate-release oral ketamine....
Aims: Ketamine and behavioural activation (BA) reduce levels of anhedonia in major depressive disorder (MDD), though neither resolves anhedonia. Combining these treatments could yield additive or even multiplicative benefits. This poster summarises the development of a PhD fellowship proposal, discussing: (1) the initial patient and public involvement (PPI) interviews, exploring views on...
Background Functional neurological disorder (FND) is a common cause of neurological symptoms including seizures and movement disorders. It can be debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder. Converging evidence suggests that other mechanisms including...
Setting up a psychedelic study can be a long, arduous, and kafkaesque process. This rapidly-developing field poses several unique challenges for researchers, necessitating a range of considerations that have not yet been standardised. Many of the complexities inherent to psychedelic research also challenge existing assumptions around, for example, approaches to psychiatric prescribing, the...
Abstract Psychosis and visual hallucinations are a prevalent non-motor symptom of Parkinson's disease, negatively affecting patients’ quality of life and constituting a greater risk for dementia. Understanding neural mechanisms associated to these symptoms is instrumental for treatment development. The mismatch negativity is an event-related potential evoked by a violation in a sequence of...
Functional neurological disorder (FND) is a common cause of neurological symptoms including seizures and movement disorders. It can be debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder. Converging evidence suggests that other mechanisms including...
Abstract Activity changes within the anterior cingulate cortex (ACC) are implicated in the antidepressant effects of ketamine, but the ACC is cytoarchitectonically and functionally heterogeneous and ketamine’s effects may be subregion specific. In the context of a double-blind randomized placebo-controlled crossover trial investigating the clinical and resting-state fMRI effects of intravenous...
Resting state connectivity studies link ketamine's antidepressant effects with normalisation of the brain connectivity changes that are observed in depression. These changes, however, usually co-occur with improvement in depressive symptoms, making it difficult to attribute these changes to ketamine's effects per se. Our aim is to examine the effects of ketamine in brain connectivity, 2 h after...
Abstract Rationale LSD is the prototypical psychedelic. Despite a clear central role of the 5HT 2a receptor in its mechanism of action, the contributions of additional receptors for which it shows affinity and agonist activity remain unclear. Objectives We employed receptor-enriched analysis of functional connectivity by targets (REACT) to explore differences in functional connectivity (FC)...
The subdivisions of the anterior cingulate cortex (ACC) - including subgenual, perigenual and dorsal zones - are implicated in the etiology, pathogenesis and treatment of major depression. We review an emerging body of evidence which suggests that changes in ACC activity are critically important in mediating the antidepressant effects of ketamine, the prototypical member of an emerging class of...
Hypnotic suggestibility is part of the wider psychological trait of direct verbal suggestibility (DVS). Historically, DVS in hypnosis has informed theories of consciousness and of conversion disorder. More recently it has served as a research tool in cognitive science and in cognitive neuroscience in particular. Here we consider DVS as a general trait, its relation to other psychological...
Acute ketamine administration has been widely used in neuroimaging research to mimic psychosis-like symptoms. Within the last two decades, ketamine has also emerged as a potent, fast-acting antidepressant. The delayed effects of the drug, observed 2–48 h after a single infusion, are associated with marked improvements in depressive symptoms. At the systems’ level, several studies have...
Ketamine as an antidepressant improves anhedonia, a pernicious symptom of depression as early as 2h post-infusion. The effects of ketamine on anhedonia are thought to be exerted via actions on reward-related brain areas—yet, these actions remain largely unknown. This study examines ketamine’s effects during the anticipation and receipt of an expected reward, after the psychotomimetic effects of...
Abstract Altered dopamine transmission is thought to influence the formation of persecutory delusions. However, despite extensive evidence from clinical studies there is little experimental evidence on how modulating the dopamine system changes social attributions related to paranoia, and the salience of beliefs more generally. 27 healthy male participants received 150mg L-DOPA, 3mg...
One of the main limitations of pharmacological fMRI is its inability to provide a molecular insight into the main effect of compounds, leaving an open question about the relationship between drug effects and haemodynamic response. The aim of this study is to investigate the acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on functional connectivity (FC) using a novel multimodal method...
Social decision-making is fundamental for successful functioning and can be affected in psychiatric illness and by serotoninergic modulation. The Prisoner's Dilemma is the archetypal paradigm to model cooperation and trust. However, the effect of serotonergic enhancement is poorly characterized, and its influence on the effect of variations in opponent behavior unknown. To address this, we...