Cannabinoid receptors,glutamate,and schizophrenia

Claude de Contrecoeur Cyrano at
Thu Dec 26 02:31:25 EST 1996

Cannabinoids receptors and schizophrenia:From Haschich to
Apparently,no research yet has been made concerning the involvement of
cannabinoids receptors and schizophrenia.However,direct introspective
observations with Cannabis sativa,together with theoretical
considerations about thoughts abnormality in schizophrenics,lead to
the strong feeling that anandamide(or other similar endogenous
cannabinoid-mimetics)is,definitely,involved in the disturbed thought
process of schizophrenics.Especially,anandamide function should be
disturbed in the hippocampus and in other areas involved in memory or
recall(the hippocampus is a structure of convergence where stored
memories in different parts of the brain converge in order to be
recalled.The hippocampus is essential for remembering,not for
memorising per se).
Cannabinoids induce a phenomenon called "illusion" which is something
completely distinct from hallucinations.Illusions are the main
phenomena which give rise to the peculiar thinking of
schizophrenics(see: Claude de Contrecoeur at:

The Illusionised Consciousness or the Schizophrenic Mind
In I845,Dr Joseph Moreau de Tours published his famous book about
haschich and madness under the title:Du Haschich et de l'Aliénation
Mentale(Masson,Paris I845,France).
This book was translated into English only in the I97O's through Raven
Press,if my memory is correct.
Moreau de Tours was a real savant,a man curious about everything and
willing to test "experimental madness", induced by haschich, in order
to try to understand real madness.
His book has been unequaled ,as far as introspection is concerned.With
this book Joseph Moreau de Tours became the father of introspective
psychopharmacology.Unfortunately,he did not have many spiritual sons
in this field until now,as some "scientists" think that rats and mice
can better report what they feel under psychotropic drugs!
Moreau de Tours ,accurately ,perceived that haschich had something to
do with real madness because haschich can induce illusions.So what are
Illusion is a state of consciousness where exogenous perceived
informational patterns are wrongly identified by memory.This error of
identification leads to false recognition of exogenous patterns
which,in turn,leads to false consciousness of events.The phenomenon of
illusion can make us conscious,"aware",of things which are
non-existent in the exogenous reality(exoreality)! It is through this
phenomenon that a schizophrenic can correctly perceive an outside
person but wrongly identify this person as someone else like,let
say,Napoléon or the Virgin Mary,etc.Illusions should not be confused
with hallucinations as these phenomena are completely
different.Hallucinations alone are not sufficient to transform a
normal person into a schizophrenic while illusions are sufficient per
se.To be crazy you just need to be illusionised! As the stimulation of
cannabinoid receptors lead to illusions,it is then very logical to
deduce that anandamide(and related endogenous compounds)should play a
crucial role in schizophrenia.This remains to be investigated but I
have no doubt that indeed disturbances of anandamide functions will be
found in schizophrenics.As illusions are also very common in normal
dreams,anandamide metabolism in the dream state should be different
from anandamide metabolism in the waking state.New medications
blocking the action of anandamide on cannabinoid receptors could well
be novel antipsychotics!

New evidence gives a boost to the above-mentionned
hypothesis:Anandamide and Glutamate

Delta 9-THC is the main illusiogenic compound of cannabis and an
agonist at central cannabinoid receptors.
The natural ligand of cannabinoid receptors,anandamide,is also an
agonist at those receptors.It was very recently found that both
anandamide and Delta 9-THC decrease glutamate neurotransmission
through a presynaptic mechanism.
Thus disturbances of anandamidic function(or similar endogenous
molecules)could,conceivably,give rise to the same psychotropic
phenomena observed with typical NMDA receptors antagonists such as
ketamine and phencyclidine.In fact,it is no wonder why phencyclidine
has been found to give symptoms similar to natural schizophrenia
because NMDA receptors antagonists are strongly illusiogenic and
illusions are at he core of the disturbed thought processes of
The action of anandamide on glutamate seems so an ideal underlying
phenomenon which could give rise to illusions such as those observed
with cannabinoids and NMDA antagonists(the differences in the
intensity of the illusions induced by these two classes of molecules
is only a question of strength,cannabinoids being weaker than NMDA
Anandamidic neurotransmission should be disturbed in schizophrenics
and,especially,in the hippocampus(as mentioned before)which is the
link between real memory and its transfer to exoreality.
In fact,as far as illusions are concerned,anandamidic disturbance
could be the main primary cause of schizophrenia as increased
anandamidic function could possibly decrease glutamate
neurotransmission in schizophrenics which,in turn,would logically
increase base-line memory metabolic activity through dopaminergic
Dopaminergic stimulation would then be the final end-result of
anandamidic dysfunction.

C.R.(Tokyo,octobre 1996)

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