Phencyclidine (PCP) is a dissociative anesthetic that induces psychotic symptoms and neurocognitive deficits in rodents similar to those observed in schizophrenia patients. PCP administration in healthy human subjects induces schizophrenia-like symptoms such as positive and negative symptoms, and a range of cognitive deficits. It has been reported that PCP, ketamine, and related drugs such as...
Preclinical studies demonstrate that rapid acting antidepressants, including ketamine require stimulation of mTORC1 signaling. This pathway is regulated by neuronal activity, endocrine and metabolic signals, notably the amino acid leucine, which activates mTORC1 signaling via binding to the upstream regulator sestrin. Here, we examined the antidepressant actions of NV-5138, a novel highly...
ScienceApril 12, 2019R. N. Moda-Sava, Mitchell H. Murdock, Puja K Parekh et al.
Why is ketamine an antidepressant? A better understanding of the mechanisms underlying the action of antidepressants is urgently needed. Moda-Sava et al. explored a possible mode of action for the drug ketamine, which has recently been shown to help patients recover from depression (see the Perspective by Beyeler). Ketamine rescued behavior in mice that was associated with depression-like...
ABSTRACT Recent modeling and empirical studies support the hypothesis that large‐scale brain networks function near a critical state. Similar functional connectivity patterns derived from resting state empirical data and brain network models at criticality provide further support. However, despite the strong implication of a relationship, there has been no principled explanation of how...
Dextromethorphan (DXM), an N-methyl-D-aspartate receptor antagonist, may have ketamine-like antidepressant effects. Dextromethorphan is extensively metabolized via cytochrome P450 (CYP) 2D6, and its half-life in extensive metabolizers is 2 to 4 hours. The purpose of this study was to evaluate the effects of DXM in combination with a moderate-to-strong CYP2D6 inhibitor antidepressant on...
The real or perceived proximity to death often results in a non-ordinary state of consciousness characterized by phenomenological features such as the perception of leaving the body boundaries, feelings of peace, bliss and timelessness, life review, the sensation of traveling through a tunnel and an irreversible threshold. Near-death experiences (NDEs) are comparable among individuals of...
Novel psychoactive substances (NPSs) have currently become a major public health concern because of relatively easy accessibility to these compounds and difficulty in identifying them with routine laboratory techniques. Here, we report the 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) case study of a 23-year-old man who developed a...
February 5, 2019Punit S. Ramrakha, Kevin P. Moore, Amir H. Sam
Abstract This chapter describes drug overdoses, the general approach, and antidotes. It includes information on overdoses of anticonvulsants, antipsychotic drugs, aspirin, benzodiazepines, beta-blockers, calcium channel blockers, carbon monoxide, cyanide, digoxin, ethanol, hypoglycaemic agents, iron, lithium, non-steroidal anti-inflammatory drugs, recreational drugs (stimulants: amphetamines,...
Impaired function in the medial prefrontal cortex (mPFC) contributes to depression, and the therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated by mPFC activity. The mPFC contains multiple types of pyramidal cells, but it is unclear whether a particular subtype mediates the rapid antidepressant actions of ketamine. Here we tested two major subtypes,...
Methoxetamine (MXE) is an N-methyl-D-aspartate (NMDA) receptor antagonist that is chemically and pharmacologically similar to other dissociative substances, such as ketamine and phencyclidine. There are reports on the misuse of MXE, which sometimes resulted in adverse consequences and death. Studies have also shown that MXE has abuse liability and stimulates dopamine neurotransmission in the...