Excitation-inhibition balance (E/I balance) is a fundamental property of cortical microcircuitry. Disruption of E/I balance in prefrontal cortex is hypothesized to underlie cognitive deficits observed in neuropsychiatric illnesses such as schizophrenia. To elucidate the link between these phenomena, we incorporated synaptic disinhibition, via N-methyl-D-aspartate receptor perturbation on...
Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus, and decreased neuronal synapses in these areas. Antidepressants can block or reverse these neuronal deficits, although typical antidepressants have limited efficacy and delayed response times of weeks to...
Methoxetamine is a dissociative anaesthetic showing pharmacodynamic similarities with its analogue ketamine, a medication with demonstrated rapid-acting antidepressant effects. Like ketamine and other arylcyclohexylamine compounds, methoxetamine is thought to be both a noncompetitive NMDA receptor antagonist and a dopamine reuptake inhibitor. Furthermore, it acts as an agonist at dopamine D2,...
Glutamatergic neurotransmission mediated by N-methyl-d-aspartate (NMDA) receptors is vital for the cortical computations underlying cognition and might be disrupted in severe neuropsychiatric illnesses such as schizophrenia. Studies on this topic have been limited to processes in local circuits; however, cognition involves large-scale brain systems with multiple interacting regions. A prominent...
Over the last 20 years, glutamatergic models of schizophrenia have become increasingly accepted as etiopathological models of schizophrenia, based on the observation that phencyclidine (PCP) induces a schizophrenia-like psychosis by blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate receptors. This article reviews developments in two key predictions of the model: first,...
The history of the chemical synthesis and animal/human pharmacology of phencyclidine is documented. From its early use as a general anesthetic, chemical model of schizophrenia, and drug of abuse, phencyclidine has had a checkered history. Research with this agent and its chemical derivatives like ketamine have provided a solid foundation for just a beginning to understanding the neuropathology...
Abstract Hallucinogens constitute one of the oldest classes of drugs used by humanity, often in the context of spiritual practices. Classic hallucinogens such as lysergic acid diethylamide (LSD), psilocybin, N,N ‐dimethyltryptamine (DMT), mescaline and 2,5‐dimethoxy‐4‐methylamphetamine (DOM) produce complex psychological and physical effects, including perceptual changes, cognitive shifts in...
Molecular and cellular studies have demonstrated opposing actions of stress and antidepressant treatment on the expression of neurotrophic factors, particularly brain-derived neurotrophic factor, in limbic structures of the brain. These changes in neurotrophic factor expression and function result in structural alterations, including regulation of neurogenesis, dendrite length and spine density...
The past decade has seen the development of an array of emerging psychoactive substances (EPS), however, there is minimal information on the extent of their use outside Europe. This study aimed to determine the extent of use of EPS from stimulant (such as mephedrone) and psychedelic classes (such as 5-methoxy-dimethyltryptamine [5-MeO-DMT]) among an Australian sample of regular ecstasy users...
DrugScope is very proud to present The media guide to drugs: key facts and figures for journalists. This new guide is intended to be a resource for journalists working across all media. The guide contains an A to Z of drugs, including information on what substances look like, how they are used, what effects they have and how many people use them in the United Kingdom. The essential Q&A section...