phencyclidine does have an effect on dopaminerginc activity and dopamine does
play an important role in schizophrenia (Souza, 1995). From this, one can see
that PCP agonists or antagonists may well be useful in treating schizophrenia.
The Crazy Crazy Man
When applying PCP psychosis to schizophrenia, a rather intriguing question
arises: What effect would PCP have on schizophrenics. The answer, of course,
raises more questions than it answers.
According to Crow, there are two types of schizophrenics, Type I and
Type II (Halberstad, 1995). Surprisingly, this model fits quite nicely when
these patients are treated with PCP. Type I schizophrenics have a “super
sensitive response to the normal amounts of endogenous PCP ligand” (Halberstad,
1995). Type II schizophrenics, on the other hand, show “Dysfunction of the
feedback look regulating PCP ligand activity, resulting in excess PCP ligand
levels” (Halberstad, 1995). Type I’s response is the result of excess A10
dopaminergic activity which makes the PCP receptor considerably more sensitive
(Halberstad, 1995). Type II’s response, the dysfunction of the feedback loop,
“is analogous to hypthalmic-pituitary-adrenal (HPA) axis dysfunction in
endogenous dysfunction (Halberstad, 1995). In general terms, a small dose
worsens Type I but leaves Type II untouched (Halberstad, 1995). A larger dose of
PCP worsens Type I to an even greater extent, while Type II shows moderate
improvement (showing the amphetamine-like activity induced by PCP) (Halberstad,
1995). From this data, it can be concluded that people who have a psychotic
response to PCP have a “biologic diathesis” (Restak, 1994) sensitivity to PCP
resembling that which Type I patients exhibit; except with a diminished
genotypic expression (Halberstad, 1995).
Curing the Ill
A number of novel drug treatment ideas have arisen from all the PCP
research, the most obvious of which is a attempted treatment of schizophrenia by
drugs which keep the NMDA channel open. This is, however, more difficult than
one would first expect. Direct stimulation on the channel is not possible, since
neurotoxicity would result from excessive calcium ion levels within the neuron
(Peterson, 1978). Instead, many of the current drugs call on glycine to
stimulate the channel indirectly. Recall that glutamate is responsible for
keeping the channel open, with help from certain reinforcing molecules like
glycine and polyamines (PCP closes the channel, and causes psychosis).
In one experiment, 11 schizophrenic patients were given 5-25mg of
glycine per day as “a concomitant drug to the neuroleptic treatment” (Souza,
1993). Four of the initial eleven patients responded favorably to this, as would
be expected. In a related open study, glycine was given to six chronic
schizophrenic patients. Two of the subjects benefited, one of which deteriorated
when denied the drug (Souza, 1993). Two other patients actually worsened as a
result of the treatment, while the remaining four showed no change (Souza, 1993).
In another study, five male schizophrenic patients were given the pro-
drug known as Milacemide (Souza, 1993), which is an acetylated version of
glycine. Milacemide is better able to cross the blood brain barrier, as compared
to pure glycine (Souza,1993). Milacemide was given to five male schizophrenic
patients after a three day medication free period (Souza, 1993). All of the
subjects worsened, three of which could not complete the study due to increases
suspiciousness, hostility, or agitation. The negative results, however, could
have been the result of the 3 day drug free period preceding the test period
(Souza, 1993).
Although no real benefit has been shown by the preceding treatments, the
principle behind their action is still strong. It has been suggested that tests
be run on other glutaminergic drugs, like polyamines (Souza, 1993). The NMDA
complex will probably be better stimulated by “direct glutamate agonists”
(Halberstad, 1995), which we may be able to synthesize in the future without
their neuron damaging effects. Regardless, we must not be dissuaded by these
disappointing results. PCP does induce schizophrenia, and there must be a
preventive or curative measure.
Conclusion It is ironic to think that a drug as terrible as phencyclidine could
hold such incredible promise in cracking the mystery of schizophrenia. Although
that day may be far in the future, PCP research has already opened many new
doors in other areas of neurologic dysfunction; such as in the treatment of
epilepsy and stroke damage. PCP has already been shown to have a number of good
uses,If not anything else, this amazing substance has given us a fascinating
look into the elegantly complex world of neurochemistry.
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