Those of you who have taken the time to read ITLAD or have attended my ITLAD lecture will know I make much of a phenomenon known as the ‘glutamate flood’ which takes place at times of high stress and, it is suggested, at the point of death. A few times I have been challenged to give supporting evidence to this statement. For the record I first encountered the ‘glutamate flood’ hypothesis in an article written by psychiatrist Dr. Karl Jansen regarding the effects of ketamine and how this can be linked to the Near-Death Experience (NDE) written in 1998. Here is a direct quote from the paper together with supporting papers:
“When glutamate is present in excess, neurones become over-excited and die. Specifically, glutamate binds to the NMDA receptors and this opens the ion channels. The dissolved salts and fluid rush into the brain cells which may swell up and burst if the degree of stimulation is excessive and prolonged. Conditions which have been proven to lead to excessive release of glutamate include low oxygen (hypoxia) and lack of a blood supply (ischaemia), the common results of a heart attack for example, or a drug overdose (another precipitant of NDE”s). Other conditions where there is an excess of glutamate include epileptic attacks, and low bood sugar levels (hypoglycaemia)(e.g. Rothman and Olney,1987).
One of the most exciting discoveries of the 1980”s was that blockade of the ion channel by ketamine prevented brain cell death from excitotoxicity (e.g. Rothman et al.,1987). When ketamine binds to the PCP receptor inside the channel, calcium cannot rush into the cell. Blockade of the NMDA binding site itself also prevents excito-toxic damage, and also results in psychedelic effects on the mental state.
This discovery led to the prediction that the brain would have a natural protective mechanism against a glutamate flood (Jansen, 1989a,b;1990a; 1996b,c; 1997a).
The current evidence suggests that preserving the brain from damage by blocking the action of glutamate produces ketamine-like psychedelic effects: the two phenomena appear to be linked.
The natural (endogenous) blocker of the NMDA receptor has now been identified. It is a peptide called N-acetyl-aspartyl-glutamate (NAAG).”
References:
Rothman, S.M and Olney, J. W. (1987). Excitotoxicity and the NMDA receptor. Trends in Neurosciences, 10, 299-302.
Rothman, S.M., Thurston, J. H., Hauhart, R. E., Clark, G. P. and Solomon., J. S. (1987). Ketamine protects hippocampal neurons from anoxia in vitro. Neuroscience, 21, 673 – 683.
