To critically evaluate published and unpublished systematic reviews and meta-analyses on the safety and efficacy of methylenedioxymethamphetamine-assisted psychotherapy for post-traumatic stress disorder. Six bibliometric databases and grey literature were searched from inception to 9 May 2024 for systematic reviews on the safety and efficacy of methylenedioxymethamphetamine (MDMA)-assisted...
Ketamine is an N-methyl-D-aspartate receptor antagonist that has shown effectiveness as a rapidly acting treatment for depression. Although advances have been made in understanding ketamine's antidepressant pharmacological and molecular mechanisms of action, the large-scale neurocognitive mechanisms driving its therapeutic effects are less clearly understood. To help provide such a framework,...
In this paper, the case study of ketamine as a new treatment for severe depression is used to outline the challenges of repurposing established medicines and we suggest potential solutions. The antidepressant effects of generic racemic ketamine were identified over 20 years ago, but there were insufficient incentives for commercial entities to pursue its registration, or support for...
AIM: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self-disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR...
The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the ‘Clinical Memorandum on...
There is an urgent need for rapidly acting antidepressants. Current therapies share a delayed onset of action, contrasting with drugs of abuse that have rapid psychotropic effects but cause tolerance and dependence. A key uncertainty is whether there is a finite speed limit imposed by the critical role of homeostatic adaptive mechanisms that underpin the efficacy and onset of available...
The self is an elusive concept. We have an intuitive sense as to what it refers to, but it defies simple definition. There is some consensus that the self can be broadly separated into what W. James referred to as the "I" and the "me" – the self that experiences, and the self that extends outwards in space and in time, allowing it to be perceived as an object1. This includes the self as...
The brain's default mode network (DMN) has become closely associated with self-referential mental activity, particularly in the resting-state. While the DMN is important for such processes, it has functions other than self-reference, and self-referential processes are supported by regions outside of the DMN. In our study of 88 participants, we examined self-referential and resting-state...
Abstract: The brain’s ‘default mode network’ (DMN) enables flexible switching between internally and externally focused cognition. Precisely how this modulation occurs is not well understood, although may involve key subcortical mechanisms, including hypothesized influences from the basal forebrain (BF) and mediodorsal thalamus (MD). Here, we used ultra-high field (7T) functional magnetic...