Biological Psychiatry
January 13, 2020
Katrin H. Preller, Patricia Duerler, Joshua B. Burt et al.
199 citations
BackgroundThe use of psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans.MethodsWe conducted a double-blind, randomized, counterbalanced, crossover study comprising 23 healthy human participants who received placebo and...
Neuron
March 1, 2019
John H. Krystal, Chadi G. Abdallah, Gerard Sanacora et al.
443 citations
Ketamine is the first exemplar of a rapid-acting antidepressant with efficacy for treatment-resistant symptoms of mood disorders. Its discovery emerged from a reconceptualization of the biology of depression. Neurobiological insights into ketamine efficacy shed new light on the mechanisms underlying antidepressant efficacy. The rapid, profound, and sustainable antidepressant effects of ketamine...
JAMA Psychiatry
March 1, 2019
Gihyun Yoon, Ismene L. Petrakis, John H. Krystal
152 citations
This study examines whether naltrexone pretreatment interferes with the antidepressant effects of ketamine.
Elife
October 25, 2018
Katrin H. Preller, Joshua B. Burt, Jie Lisa Ji et al.
416 citations
Background: Lysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor contributions to its neurobiological effects remain unknown. Methods: We therefore conducted a double-blind, randomized, counterbalanced, cross-over studyduring which 24 healthy human participants received...
Depression and Anxiety
April 6, 2016
Chadi G. Abdallah, Thomas G. Adams, Benjamin Kelmendi et al.
204 citations
Major depressive disorder (MDD) is a common and debilitating psychiatric disorder. Traditional antidepressants are of limited efficacy and take weeks to months to yield full therapeutic effects. Thus, there is a clear need for effective rapid-acting antidepressant medications. The N-methyl-d-aspartate receptor (NMDA-R) antagonist, ketamine, has received a great deal of attention over the last...
Annals of the New York Academy of Sciences
February 27, 2015
Chadi G. Abdallah, Lynnette A. Averill, John H. Krystal
117 citations
The discovery of ketamine's rapid and robust antidepressant effects opened a window into a new generation of antidepressants. Multiple controlled trials and open-label studies have demonstrated these effects across a variety of patient populations known to often achieve little to no response from traditional antidepressants. Ketamine has been generally well tolerated across patient groups, with...
Journal of Psychiatric Research
December 24, 2014
Ke Xu, John H. Krystal, Y. Ning et al.
65 citations
Objective Studies of the effects of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, ketamine, have suggested similarities to the symptoms of schizophrenia. Our primary goal was to evaluate the dimensions of the Positive and Negative Syndrome Scale (PANSS) in ketamine users (acute and chronic) compared to schizophrenia patients (early and chronic stages). Method We conducted...
Annual Review of Medicine
October 23, 2014
Chadi G. Abdallah, Gerard Sanacora, Ronald S. Duman et al.
420 citations
Ketamine is the prototype for a new generation of glutamate-based antidepressants that rapidly alleviate depression within hours of treatment. Over the past decade, there has been replicated evidence demonstrating the rapid and potent antidepressant effects of ketamine in treatment-resistant depression. Moreover, preclinical and biomarker studies have begun to elucidate the mechanism underlying...
PLoS One
June 12, 2013
Philip R. Corlett, Victoria C. Cambridge, Jennifer M. Gardner et al.
104 citations
Delusions are the persistent and often bizarre beliefs that characterise psychosis. Previous studies have suggested that their emergence may be explained by disturbances in prediction error-dependent learning. Here we set up complementary studies in order to examine whether such a disturbance also modulates memory reconsolidation and hence explains their remarkable persistence. First, we...
Cerebral Cortex
November 29, 2012
John D. Murray, Alan Anticevic, Mark G. Gancsos et al.
278 citations
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...
Proceedings of the National Academy of Sciences
September 25, 2012
Alan Anticevic, Mark G. Gancsos, John D. Murray et al.
260 citations
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...
Schizophrenia Bulletin
September 1, 2012
Bita Moghaddam, John H. Krystal
Here, we describe our collaborative efforts to use N-methyl-d-aspartate (NMDA) receptor antagonists as a translational tool to advance our understanding of the pathophysiology of schizophrenia and identify potential new targets for treatment of schizophrenia. We began these efforts in the late 1980s with a keen sense that, in both human and animal studies, we needed to move beyond the dopamine...
Progress in neuro-psychopharmacology & biological psychiatry
January 15, 2011
Jaime E C Hallak, Serdar M Dursun, Daniel C Bosi et al.
Interactions between glutamatergic and endocannabinoid systems may contribute to schizophrenia, dissociative states, and other psychiatric conditions. Cannabidiol (CBD), a cannabinoid-1/2 (CB1/2) receptor weak partial agonist or antagonist, may play a role in the treatment of schizophrenia. This study tested the hypothesis that CBD would attenuate the behavioral effects of the NMDA receptor...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
September 2008
Deepak Cyril D'Souza, Mohini Ranganathan, Gabriel Braley et al.
Cannabis is one of the most widely used illicit substances and there is growing interest in the association between cannabis use and psychosis. Delta-9-Tetrahydrocannabinol (Delta-9-THC) the principal active ingredient of cannabis has been shown to induce psychotomimetic and amnestic effects in healthy individuals. Whether people who frequently use cannabis are either protected from or are...
Archives of General Psychiatry
September 1, 2005
John H. Krystal, Edward Perry, Ralitza Gueorguieva et al.
323 citations
BACKGROUND: In healthy individuals, ketamine hydrochloride and amphetamine sulfate produce cognitive, behavioral, and subjective effects resembling endogenous psychoses. Studying the comparative and interactive effects of these agents may provide insights into the roles of the glutamate and monoamine systems in psychosis and cognition. OBJECTIVES: To directly compare the effects of ketamine and...
American Journal of Psychiatry
October 1, 2004
Ismene L. Petrakis, Diana Limoncelli, Ralitza Gueorguieva et al.
143 citations
OBJECTIVE: A family history of alcoholism is a risk factor for the development of ethanol dependence. Ethanol is an antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, and alterations in NMDA receptor function are thought to be involved in ethanol abuse and dependence. The purpose of this study was to determine in healthy individuals with no ethanol dependence whether response to...
Hippocampus
October 1, 2001
John W. Newcomer, John H. Krystal
238 citations
N-methyl-D-aspartate (NMDA) receptor hypofunction is associated with a range of effects on cognition and behavior in whole animal and human studies. NMDA receptor hypofunction within the brain, which can be induced experimentally in vivo using NMDA receptor antagonist drugs, produces adverse effects on memory function. The results suggest that NMDA receptor hypofunction can preferentially...
Archives of General Psychiatry
March 1, 2000
Amit Anand, Dennis S. Charney, Dan A. Oren et al.
425 citations
BACKGROUND: The cognitive, behavioral, and mood effects of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine, have been used to study the effects of NMDA receptor dysfunction. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as...
October 1, 1999
R. Andrew Chambers, J. Douglas Bremner, Bita Moghaddam et al.
140 citations
Dissociative cognitive and perceptual alterations commonly occur at the time of traumatization and as an enduring feature of post-traumatic stress disorder (PTSD). After stress exposure, dissociative symptoms are a predictor of the development of PTSD. Recent preclinical data suggest that stress stimulates the cortico-limbic release of glutamate. The glutamate that is released during stress in...
Pharmacopsychiatry
July 1, 1998
Walid Abi‐saab, Deepak C D'Souza, Bita Moghaddam et al.
Drug models have been extensively used to study the pathophysiology of schizophrenia. While they provide good insight into the neurobiology of this disorder, they have several shortcomings, which if known, help in the interpretation of results. In this paper we will discuss these shortcomings in general, and in relation to the N-methyl D-aspartate antagonist model for schizophrenia. This model...
Journal of Traumatic Stress
1998
J. Douglas Bremner, John H. Krystal, Frank W. Putnam et al.
826 citations
The purpose of this study was to develop an instrument for the measurement of present-state dissociative symptoms, the Clinician Administered Dissociative States Scale (CADSS). Reported here are interrater reliability and internal consistency of the CADSS, validity as assessed by comparisons with other instruments for the assessment of dissociation, and sensitivity of the CADSS to discriminate...
Archives of General Psychiatry
March 1, 1994
John H. Krystal
3,339 citations
BACKGROUND: To characterize further behavioral, cognitive, neuroendocrine, and physiological effects of subanesthetic doses of ketamine hydrochloride in healthy human subjects. Ketamine, a phencyclidine hydrochloride derivative, is a dissociative anesthetic and a noncompetitive antagonist of the N-methyl-D-aspartate subtype of excitatory amino acid receptor. METHODS: Nineteen healthy subjects...
The American Journal of Drug and Alcohol Abuse
1992
John H. Krystal, Lawrence H. Price, Charles Opsahl et al.
171 citations
3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a selective serotonin (5-HT) neurotoxin in animals. There is now preliminary evidence in humans of 5-HT deficits associated with extensive use of MDMA. In order to begin to describe the cognitive and mood effects of chronic MDMA use, nine individuals with extensive MDMA use histories were studied. Despite the absence of memory deficits on...