1) The internal experience of NMDA antagonists on human consciousness clearly does not resemble the critical elements which define schizophrenia, based on the author's experience.
2) The common name for NMDA antagonists is "dissociative drugs" or simply "dissociatives". This term is correct as these chemicals induce a characteristically dissociative state.
3) Depersonalization disorder is reproduced in normal individuals by NMDA antagonists. Descriptions of derealization and depersonalization from a person with this condition who has never taken drugs are also the only found to describe well the effects of NMDA antagonists. The negative symtomps of schizophrenia and strong depersonalization are identical to external observation.
4) Individuals with dissociative disorders (including borderline conditions) can show transient psychosis-like behaviour. Dissociative anaesthetics can induce a state in which the intoxicated individual is operating in a mode akin to a waking dream, which may be confused as schizophrenic in nature.
5) Far from lacking adverse sequelae ketamine like all dissociative drugs has a range of deleterious effects on the human organism.
6) The bulk of the evidence used to support the NMDA antagonist hypothesis involves trying to quantify by external observation elements in conciousness that only appear internally. This is parallel to determining what the inside of a box looks like by measuring the outside.
7) The involvement of opioids in schizophrenia has been proposed as early as the 1970's without having to resort to use of psychotomimesis as evidence.
8) Salvinorin A, a kappa opioid agonist, is a true psychotomimetic, specifically replicating the experience of schizophrenia.
9) Journal evidence supports the connection between kappa opioids and the dopaminergic and NMDA/glutamatergic systems:
i) Kappa opioids have been demonstrated to selectively control dopaminergic neurons projecting to the prefrontal cortex.
ii) A recent study suggests that a kappa opioid antagonist counteracts the effect of an NMDA antagonist in mice.
iii) Kappa opioid agonists have been shown to inhibit glutamatergic transmission in the nucleus accumbens shell.
iv) Kappa-2 Opioid Receptors in Limbic Areas of the Human Brain Are Upregulated by Cocaine in Fatal Overdose Victims
10) Ketamine is a kappa opioid agonist, lesser to it's action as an NMDA antagonist. This has blatant impacts on the validity of research. The stereoisomeric variation in this explains the massive differences between products witnessed by ketamine addicts.
11) The mixed mu-agonist kappa-antagonist buprenorphine showed antipsychotic activity in one clinical trial.
12) It has already been suggested that kappa opioid antagonists could serve as useful medications. Kappa-antagonists could serve as the proper therapeutic adjuncts for controlling schizophrenic psychosis, obsoleting the chemicals currently used and proving superior to those in development (although one wonders about the effect of NMDA 'enhancers' on dissociative and post-traumatic conditions).
[Revised 8/4/07]
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During and following the writing of this the author fell into a severe psychosis. Apologies must be made for the harshness of the original wording. The author is currently under medical care and very appreciative of the hard work of the doctors and medical staff and the difficulties they face. They are very much doing their best with the tools they have. Researchers have also been doing all they are able to try and solve the puzzle, but the tremendous problems involved in quantifying changes in consciousness are a very difficult barrier to overcome.
The author having experienced a full psychosis following the original writing is now even more certain that it is the kappa opioid system that is most implicated in the critical sensory distortions that define schizophrenia. NMDA antagonists emulate well certain aspects of psychosis, such as changes in frame of reality; the class termed 'psychedelics' affecting serotonin receptors emulate much better other aspects such as spiritual thinking and overconnectedness of ideas, events, numbers, and such; dopaminergics the paranoia, overflow of ideas, over-focus on specific things and exaggerated self-importance. Psychosis seems to be a connected cascade of receptor dysfunction - it is chronic and not acute upregulation of dopamine which consistently induces it; from the author's reckless past it can be said with certainty that no single psychotropic substance emulates a full psychosis. Acute administration of a kappa opioid agonist produces a set of effects which very strongly resembles the distinct disturbances of schizophrenia proper.
-We apologize for the inconvenience.
Anonymous
[7/7/07]
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Much of the schizophrenia research community has concluded that NMDA antagonist drugs accurately replicate the disorder. This a small collection of critical evidence demonstrating that Salvinorin A is the most accurate mimic of the condition.
