Mechanism of Action and Therapeutic Potential
Jansen, K. L. R. (1996) Using ketamine to induce the near -death
experience: mechanism of action and therapeutic potential. Yearbook for
Ethnomedicine and the Study of Consciousness (Jahrbuch furr Ethnomedizin
und Bewubtseinsforschung) Issue 4, 1995 (Ed.s C. Ratsch; J. R. Baker);
VWB, Berlin, pp55-81.
Using Ketamine to Induce the Near-Death Experience:
Dr. Karl L. R. Jansen,
Mechanism of Action and Therapeutic Potential
63 Denmark Hill
London SE5 8AZ
About the Author
Dr. Karl Jansen was born in New Zealand and trained in medicine at the
University of Otago. After registering as a medical practitioner, he
proceeded to carry out brain research at the University of Auckland as a
research fellow of the New Zealand Medical Research Council. At this time
he became interested in ketamine and its effects and published his first
observations in this area, and also in antipodean use, users and
consequences of psilocybin-containing mushrooms. He then went to the United
Kingdom, and attended the University of Oxford (New College) were he
completed a Doctor of Philosophy in Clinical Pharmacology. He was the Glaxo
Fellow at Green College. On completion of his studies at Oxford, he went to
the Maudsley Hospital and London Institute of Psychiatry to complete his
training as a psychiatrist. He is now a member of the Royal College of
Psychiatrists. His current research interests are the ketamine model of the
near-death experience and the consequences of long-term, high dose
recreational use of Ecstasy (MDMA).
He would be interested to receive correspondence concening the subject of
this paper. You can email him as: K@BTInternet.COM
Near-death experiences (NDE's) can be induced using the dissociative drug
ketamine. Advances in neuroscience have recently provided us with new
insights as to the mechanisms involved at the mind -brain interface. On the
'brain' side, it is now clear that these NDE's are due to blockade of brain
receptors (drug binding sites) for the neurotransmitter glutamate. These
binding sites are called the N-methyl-D-aspartate (NMDA) receptors.
Conditions which precipitate NDE's (low oxygen, low blood flow, low blood
sugar, temporal lobe epilepsy etc.) have been shown to release a flood of
glutamate, over-activating NMDA receptors. This overactivation can kill
brain cells ('excito' toxicity). Ketamine prevents excitotoxicity.
Conditions which trigger a glutamate flood may also trigger a flood of
ketamine-like brain chemicals which bind to NMDA receptors to protect
cells, leading to an altered state of consciousness like that produced by
ketamine. On the 'mind' side, induction of NDE's has psychotherapeutic
value via several routes which will be explored in this article.
To facilitate reading, in some cases references have been grouped together
at the end of a paragraph.
The near-death experience (NDE) is a phenomenon of wide general interest.
Despite its association with sensationalist media reports, populist books
of doubtful scientific value, and a series of dubious Hollywood films, the
NDE is still of considerable importance to medicine, neuroscience,
neurology, psychiatry, psychology and, more controversially, philosophy and
theology (Stevenson and Greyson, 1979; Greyson and Stevenson, 1980; Ring,
1980; Sabom, 1982; Jansen, 1989a,b, 1990b, 1995, 1996). Philosophical and
theological issues are beyond the scope of the present discussion, which is
based within the scientific paradigm and is thus best assessed from within
Recent advances in neuroscience are bringing us closer to a brain-based
understanding of the NDE as an altered state of consciousness. This
discussion does not address the issue of whether there is life after death,
but does argue that NDE's are not evidence for life after death. This would
be appear to be self-evident on logical grounds: death is defined as the
final, irreversible end. The Oxford English Dictionary (Sykes, 1982)
defines death as the 'final cessation of vital functions'.According to this
definition, 'Returnees' did not die - although their minds, brains and
bodies may have been in a highly unusual state for a period of time. If
these definitions are not accepted, then we need a new terminology to
describe these states.
There is now evidence from thousands of studies relating brain events to
alterations in mental state that 'mind' results from neuronal activity.
These studies range from observing the results of directly stimulating the
brain with electrodes, for example the pioneering work of the neurosurgeon
Wilder Penfield, to the most recent studies using magnetic resonance
imaging to observe brain activity, for example to demonstrate activity in
the temporal lobe while schizophrenics are experiencing auditory
hallucinations (McGuire et al., 1995). The dramatic effects on the mind
which result from the action of hallucinogenic drugs in the brain, effects
which can include profound religous experiences, provide further evidence
for the dependance of mind upon neurochemical and neuroelectrical events
(Grinspoon and Bakalar, 1981). However, the dimension in which mind itself
exists remains a mystery.
Within a scientific paradigm, it is not possible that "the spirit rises out
of the body leaving the brain behind, but somehow still incorporating
neuronal functions such as sight, hearing, and proprioception" (Morse,
1989). To believe that this is possible, we must leave the realm of science
and adopt a wholly different paradigm.
The Near-Death Experience: Typical Features
There is no internationally agreed set of criteria which define the NDE as
exists, for example, for psychiatric disorders. Some critics of
neurobiological models have dismissed them because a feature of the NDE
which they believe to be important may not have been fully accounted for by
the model being proposed, although it may well be that the statistically
determined key features of the NDE (a consensus view) would not include
those features. Just as with classification in psychiatry, it is important
to reach an international consensus and avoid the sectarian views of a few.
Neurobiological models should not be disregarded because of obscure and
exceptional cases which cannot currently be explained.
The typical features of a 'classic' NDE include a sense that what is
experienced is 'real' and that one is truly dead, ineffability (i.e. a
sense that what is experienced cannot be described using language, 'beyond
words'), timelessness, analgesia, apparent clarity of thought and feelings
of calm and peace, although some NDE's have been disturbing and
frightening. There may be a perception of separation from the body
(out-of-body experiences). Common hallucinations include landscapes, people
including partners, parents, teachers and friends (who may be alive at the
time), and religous and mythical figures including angels and a
representation of 'God' as light. Transcendant mystical states are common.
Memories frequently emerge into consciousness, although the organisation of
these into a 'life review' is a relatively rare phenomenon. Hearing noises
during the initial part of the NDE has been described - the significance of
this feature will be discussed later (Noyes and Kletti, 1976a; Morse et
al., 1985; Osis and Haraldsson, 1977; Greyson and Stevenson, 1980; Ring,
1980; Sabom, 1982; Greyson, 1983).
Ring (1980) classified NDE's on a 5 stage continuum:
1. feelings of peace and contentment;
2. a sense of detachment from the body;
3. entering a transitional world of darkness (rapid movements through tunnels: 'the tunnel experience');
4. emerging into bright light; and
5. 'entering the light'.
60% experienced stage 1, but only 10% attained stage 5 (Ring, 1980). As
might be predicted in a mental state with a neurobiological origin, mundane
accounts with less symbolic meaning also occur, e.g. children who may 'see'
their schoolfellows rather than God and angels (Morse, 1985).
The intravenous administration of 50 - 100 mg of ketamine can reproduce all
of the features which have commonly been associated with NDE's.
Intramuscular administration also results in NDE's, but events evolve at a
slower pace and are longer lasting (Domino et al., 1965; Rumpf ,1969;
Collier, 1972; Siegel,1978, 1980,1981; Stafford, 1977; Lilly, 1978;
Grinspoon and Bakalar, 1981; White, 1982; Ghoniem et al., 1985; Sputz,
1989; Jansen, 1989a,b, 1990b, 1993, 1995, 1996).
Mounting evidence suggests that the reproduction/induction of NDE's by
ketamine is not simply an interesting coincidence. Exciting new discoveries
include the major binding site for ketamine on brain cells, known as the
phencyclidine (PCP) binding site of the NMDA receptor (Thomson et al.,
1985), the importance of NMDA receptors in the cerebral cortex,
particularly in the temporal and frontal lobes, and the key role of these
sites in cognitive processing, memory, and perception. NMDA receptors play
an important role in epilepsy, psychoses (Jansen and Faull, 1991), and in
producing the cell death which results from a lack of oxygen, a lack of
blood, and from epileptic fits (excitotoxicity). This form of brain cell
damage can be prevented by administration of ketamine. Other key
discoveries include that of chemicals in the brain called 'endopsychosins'
which bind to the same site as ketamine, and the role of ions such as
magnesium and zinc at this site (Anis et al., 1983; Quirion et al., 1984;
Simon et al., 1984; Benveniste et al., 1984; Ben-Ari,1985; Thomson, 1986;
Coan and Collingridge, 1987; Collingridge, 1987; Contreras et al., 1987;
Cotman and Monohan, 1987; Rothman et al., 1987; Mody et al., 1987; Nowak et
al., 1984; Quirion et al., 1987; Westbrook and Mayer, 1987; Sonders et al.,
1988; Barnes,1988; Choi,1988; Monaghan et al., 1989; Jansen et al.,
1989a,b,c, 1990a,b,c, 1991a,b,c, 1993, 1995, 1996).
Ketamine administered by intravenous injection is capable of reproducing
all of the features of the NDE which have been commonly described (Domino
et al., 1965; Rumpf, 1969; Collier, 1972; Siegel,1978, 1980, 1981;
Stafford, 1977; Lilly, 1978; Grinspoon and Bakalar, 1981; White, 1982;
Ghoniem et al., 1985; Sputz, 1989; Jansen, 1989a, b,1990b, 1991c, 1993,
1995, 1996; Kungurtsev, 1991).
Unfortunately, the study in which persons who have had NDE's are given
ketamine and asked to compare the two experiences has yet to be carried
out, although the psychological effects of ketamine have been well
documented in numerous clinical studies by anaesthetists (see Domino,
1992). Information in the area of ketamine and NDE's remains largely
anecdotal, and some of these references are necessarily to secondary
sources. The present author has experienced several NDE's and has also been
administered ketamine as an anesthetic and within experimental paradigms.
The NDE's and ketamine experiences were clearly the same type of altered
state of consciousness. Ketamine repeatedly produced effects which were
like the NDE's described by Moody (1975), Noyes and Kletti (1976a), Greyson
and Stevenson (1980), Ring (1980), Sabom (1982) and Morse et al., (1985).
Ketamine reproduced travel through a tunnel (sometimes described as 'the
plumbing of the world', or in mundane terms such as 'like being on a subway
train'), emergence into the light, and a 'telepathic' exchange with an
entity which could be described as 'God'. Neither the NDE's nor the
ketamine experiences bore any resemblance to the effects of psychedelic
drugs such as dimethyltryptamine (DMT; also administered to the author in
experimental paradigms) and lysergic acid diethylamide (LSD).
Ketamine: Typical Features
Ketamine is a short-acting, hallucinogenic, 'dissociative' anaesthetic.
The anaesthesia is the result of the patient being so 'dissociated' and
'removed from their body' that it is possible to carry out surgical
procedures. This is wholly different from the 'unconsciousness' produced by
conventional anesthetics, although ketamine is also an excellent analgesic
(pain killer) by a different route (i.e. not due to dissociation). Ketamine
is related to phencyclidine (PCP). Both drugs are arylcyclohexylamines -
they are not opioids and are not related to LSD. In contrast to PCP,
ketamine is relatively safe, is much shorter acting, is an uncontrolled
drug in most countries, and remains in use as an anaesthetic for children
in industrialised countries and all ages in the third world as it is cheap
and easy to use (White et al., 1982). Anaesthetists prevent patients from
having NDE's ('emergence phenomena') by the co-administration of sedatives
which produce 'true' unconsciousness rather than dissociation (Reich and
The altered state of consciousness resulting from ketamine administration
is very different from that produced by psychedelic drugs such as LSD and
DMT (Grinspoon and Bakalar, 1981).
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