Secondary Schizophrenia (56 page)

other psychiatric disorder
[22, 23,
30].

In addition to acute intoxication syndromes,
A point of disagreement in the clinical literature
PCP induces psychotic disorder that is very similar
concerns the effectiveness of dopamine D2 receptor
to schizophrenia or schizoaffective disorder in the
(D2R) antagonist antipsychotics in the treatment of
absence of delirium
[9, 14, 20, 21, 22, 23, 24, 25,

acute PCP psychosis. Some studies concluded benzo-

26, 27, 28, 29]
. The duration of PCP-related psy-diazepines were preferable to haloperidol or chlorpro-chosis bears no relationship to ingested dose or drug
mazine in PCP intoxication whereas others favored
half-life. It characteristically shows sudden resolution
haloperidol
[32, 33, 34, 35].
Apart from one group
within 2 to 4 weeks
[22, 29]
, although on occasion
[33, 35],
most agreed that antipsychotic and seda-persists for months. Patients with PCP-related psy-tives may reduce agitation; however, no pharmaco-chosis could not be distinguished from schizophre-logical treatments appeared to shorten the course of
nia patients on the basis of presenting symptoms
[17,

the psychotic illness
[10, 25].
Luisada and Brown
[27]

23]
. All domains of schizophrenic symptomatology
noted that in the cases subsequently rediagnosed with
seemed to be represented. Prominent positive symp-schizophrenia, acute response to antipsychotic drugs
toms were reported: paranoia; and persecutory and
was faster and superior after rediagnosis than during
grandiose delusions
[23, 25, 26, 27,
30],
often with
the first PCP-induced episode of psychosis. The equiv-bizarre Schneiderian qualities
[17, 28,
31];
and hallu-ocal response of PCP psychosis to D2R antagonists was
cinations in all modalities
[17, 19, 23, 25, 26, 27,
30,

the first clue that PCP psychosis may not be primarily
32].
Formal thought disorder with loosening of asso-linked to dopamine dysregulation.

ciations, cognitive disorganization, perseveration, or
Experimental studies using PCP in hospitalized
thought blocking occurred [14, 17, 20, 25, 26, 27, 30].

patients with chronic schizophrenia supported the
Catatonic behavior in a variety of forms was almost
view that the psychotomimetic effect of PCP was
universally present with PCP psychosis: inappropri-directly related to mechanisms producing the symp-ate and unpredictable behavior; excitement and vio-toms of schizophrenia
[36, 38].
Luby and colleagues
lence; nudism; mannerisms and stereotypies; and cata-

[36]
reported that immediately after IV PCP, patients
tonic posturing and mutism
[10, 14, 17, 18, 19, 23, 25,

showed an acute intensification of thought disorder
26, 27, 29,
30, 32].
Features resembling negative symp-and inappropriate affect: “it was as though . . . the acute
toms also occurred: blunted affect
[19]
; apathy and
phase of their illness had been reinstated.” Chronic
emotional disengagement
[14];
social withdrawal and
patients frequently manifested symptom relapses per-autistic behavior
[20, 23, 27];
and amotivation
[14, 20,

sisting for more than a month after a single IV dose
23, 27].

of PCP, indicating that PCP may act on a funda-Despite marked similarities between PCP psy-

mental disease process. That is, PCP exaggerated pre-chosis and schizophrenia, cross-sectionally, there were
existing, or precipitated an acute relapse of previously
atypical features: a predominance of visual or haptic
experienced, phenomenology rather than added qual-hallucinations over auditory hallucinations; distortion
itatively different psychotic symptoms. Response to
of time appreciation and body image disturbance; and
PCP in patients was distinctly different to that with
prominent somatosensory deficits, especially dimin-LSD or mescaline that produced a milder and brief
ished proprioception and pain perception
[6,
31].
In
change in the level of symptoms, mainly by adding
addition, there were differences in psychiatric history
qualitatively different symptoms such as kaleidoscopic

with a relatively high proportion of patients not hav-visual hallucinations
[36, 37, 39, 40].
Providing the first
Organic Syndromes of Schizophrenia – Section 3

suggestion that prefrontal mechanisms were directly
sory distortions were experienced, like hearing your
related to PCP effects, Itil and colleagues
[38]
found
voice “seem to come from a distance – as if some-that leucotomized patients with schizophrenia did not
one else were speaking,” and yet intellectually know-show as marked a response to PCP compared to unleu-ing that it was yourself speaking. Feelings of passiv-cotomized patients.

ity emerged so that “the subject saw his arms and legs
Experimental studies using PCP in human vol-

move and yet did not have the feeling that he him-unteers (healthy volunteers) also supported the view
self was making these movements.” A profound sense
that PCP comprehensively induced symptoms resem-of apathy and amotivation accompanied the PCP-bling schizophrenia
[36, 41, 42, 43, 44].
Luby and
induced psychotomimetic effects. Bakker and Amini
colleagues
[36]
gave 9 healthy volunteers PCP in
[44]
hypothesized that PCP produced a converse psy-a subanesthetic dose (0.1 mg/kg IV). All subjects
chic state to that induced by LSD and psilocybin; PCP

experienced “body image changes” (impaired abil-appeared to be a “negative” state with “decreased”

ity to distinguish between self and nonself stimuli,
functions whereas LSD and psilocybin appeared to be
feelings of depersonalization, and a sense of unreal-

“stimulating” of activity.

ity), “estrangement” (profound sense of aloneness or
Moreover, early neurocognitive studies in healthy
isolation, of being detached from the environment),
volunteers demonstrated PCP-induced deficits resem-and “disorganization of thought” (inability to main-bling those seen in schizophrenia. Rosenbaum and
tain a set, frequent loss of goal ideas, impairment of
colleagues
[41]
compared three groups of healthy vol-abstract attitude, blocking, neologisms, jumbled word-unteers, 10 receiving PCP (0.1 mg/kg IV), 10 receiving and echolalia). Most subjects experienced nega-ing LSD orally (1
µ
g/kg), and 5 receiving 500 mg amotivism, and hostility (child-like oppositional behav-barbital sodium IV (amphetamine 15 mg added to
ior and catatonia-like reactions); about one third
counter drowsiness associated with the barbiturate).

showed repetitive motor behaviors (rhythmic body
Using a crude measure of attention, only PCP (i.e.,
movements, including rocking, head-rolling, and gri-not LSD or barbiturate) produced a deficit equiva-macing). In another study of 12 healthy volunteers,
lent to that observed on the same test in patients
PCP (0.075–0.1 mg/kg IV) induced positive symp-with schizophrenia. On a motor learning task, the per-toms (auditory hallucinations and thought disorder),
formance of only the PCP-treated healthy volunteers
negative symptoms (blunting, apathy, and amotiva-dropped to the level of patients with schizophrenia.

tion), catatonic features (psychomotor retardation,
Cohen and colleagues
[43]
compared the effects of
negativism, and catatonic immobility), and cogni-PCP, LSD, and amobarbital sodium (amphetamine 15

tive deficits (associative learning and abstract reason-mg added) in three groups of healthy volunteers. In
ing deficits)
[42].
In contrast to LSD or mescaline,
a test of symbolic thinking (proverb interpretation),
PCP in healthy volunteers induced perseveration and
only PCP subjects (i.e., not LSD or barbiturate) showed
concreteness and nystagmus: in common with LSD

deficits in symbolic thinking quantitatively equivalent
and mescaline, PCP induced body image disturbance,
to those seen in groups of patients with schizophrenia.

depersonalization, and disturbances in time appreci-Similar findings were made in relation to a test of sus-ation
[42]
. One study of 7 healthy volunteers given
tained attention (serial sevens).

12 mg PCP by slow IV injection provided detailed
In summary, the psychotomimetic effects of PCP

descriptions of phenomenology
[44].

were first recognized as emergence phenomena when
After a brief period of disorientation cleared, PCP

it was used as an anesthetic. During a PCP abuse
caused marked cognitive deficits affecting “the func-epidemic in the United States, it became evident
tion that combines, unifies, and integrates all available
that PCP induced formal psychotic disorder, even
information into a field that is meaningful” and pre-in individuals without evidence of predisposition
venting “goal-directed behavior.” Formal thought disto schizophrenia. The phenomenology of the psy-order (both loosening and concreteness) was apparent,
chotomimetic effects of PCP was schizophrenia-like
including “catatonic-like perseveration.” Sensory fil-in range and quality, whether observed as anes-tering deficits occurred so that the subject “was unable
thetic emergence phenomena, presenting symptoms of
to focus actively on particular areas of his perceptual
PCP-induced psychotic disorder, or behavioral change
field [and] had become a victim of all inflowing stimuli
induced by experimental use of PCP in patients with

but could not screen out the irrelevancies.” Also, sen-schizophrenia or healthy volunteers. Clinicians who
Chapter 10 – Psychotomimetic effects of PCP, LSD, and Ecstasy

observed PCP-induced symptoms recognized signs
or illusions, “weird trips,” and occasionally delirium
that Bleuler (“loosening” plus “concreteness”) and
[48].
Between 10%–15% of postperative patients show
Kraepelin (“weakening . . . volition” plus “loss of inner
hallucinatory reactions
[53, 54].
Ketamine emergence
unity of the activities of intellect, emotion and voli-phenomena are dose dependent and age related, with
tion”) deemed primary to – and processes (e.g., sen-an incidence of less than 10% in patients less than
sorimotor gating
[45])
that psychologists considered
16 years old
[48]
. Compared to standard anesthesia
characteristic of – schizophrenia. Because PCP was
(halothane/nitrous oxide), ketamine does not cause
made illegal for use in human research in 1965,
an excess of emergence reactions in children
[55].

no studies measuring the effect of PCP on putative
In adults, pretreatment with droperidol or haloperi-biomarkers of schizophrenia (e.g. prepulse inhibition
dol is inferior to benzodiazepines in preventing vivid
[PPI], smooth pursuit eye movement [SPEM], P50

emergence reactions and delirium following ketamine
suppression or mismatch negativity [MMN]) or func-

(reviewed in [48]). In summary, when used as an anes-tional neuroimaging measures were carried out in
thetic ketamine induces emergent psychotomimetic
patients with schizophrenia or healthy volunteers. This
effects qualitatively similar to PCP but quantitatively
type of human research had to await the introduction
substantially less intense, in line with its more than
of ketamine, a safer and less potent psychotomimetic
10-fold lower PCP-like activity
[56]
and about 30-fold
analogue of PCP.

lower NMDA receptor complex binding affinity
[57,

58].

Despite warnings about its abuse potential
[59],

Ketamine

ketamine eventually appeared on the streets (known
Analogues of PCP were researched as alternative disas ‘“Special K, “Vitamin K,” or “K”) in the early
sociative anesthetic agents that might have fewer
1970s
[13,
60]
in the same way that PCP did in the
adverse reactions than PCP, the most important being
1960s. In 1978 ketamine was authoritatively described
ketamine [2-(2-chlorophenyl)-2-(methylamino)-cyclo-as the “ultimate psychedelic”
[61].
Ketamine is typ-hexanone]. Ketamine was first synthesized in 1961,
ically inhaled or injected intramuscularly. Ketamine
first tested in human volunteers in 1964
[46],
and
users try to achieve or “fall into” a “k-hole” of social
first approved for general clinical use in 1970. It is
detachment lasting up to an hour. This experience
used intravenously (analgesic dose, 1–2 mg/kg; anes-includes a distorted sense of space, so that a small
thetic dose, 5–10 mg/kg), intramuscularly (analgesic
room appears the size of a football field, and an
dose, 1.5–2 mg/kg; anesthetic dose, 4.0–6.0 mg/kg),
indistinct awareness of time, so that a few minutes
and less frequently as an oral (100–300 mg/kg) anes-seems like an hour
[62].
Physical immobilization and
thetic
[47, 48].
Ketamine is a highly lipid soluble and
disengagement from time and space are associated
readily crosses the blood-brain barrier, inducing CNS