Schizophrenia-like symptoms have been experimentally produced in humans by a single, large dose of amphetamine or by relatively low level, but continuous administration of the drug.

In animal studies of the psychotomimetic properties of amphetamine, high doses and, in particular, repeated daily-injection drug schedules have often been used. However, amphetamine psychosis is not always a prominent effect of repeated intake drug schedules in humans and available clinical evidence suggests that psychosis develops more readily when the drug is taken in a continuous fashion over longer periods.

The state produced by single large doses of amphetamine, although clearly abnormal, has been said to bear less resemblance to schizophrenia than the delayed paranoid symptoms developing after longer periods of continuous intake.

In the present experiments we have studied the behavioral effects of 7 to 14 days of continuous administration of amphetamine to monkeys (Cercopithecus aethiops) using subcutaneously implanted silicone capsules releasing approximately .7 to 1.5 mg/kg/day of d-amphetamine base. Around-the-clock TV monitoring of the animals revealed a general biphasic sequence of drug effects, although considerable individual variation occurred:

a) an "acute" phase dominated by stereotyped movements and/or prolonged staring, lasting for 2 to 5 days;
b) a "late" phase peaking during days 5 to 10 after capsule implantation and characterized by highly individual, but striking sequences of:

(1) Attack or sudden threat reactions directed at invisible objects;
(2) rapid orienting and flight behavior without apparent cause;
(3) sudden startle reactions;
(4) prolonged vocalization;
(5) visual tracking of invisible objects, sometimes involving coordinated patterns of "eating behavior" and
(6) prolonged and rapid grooming directed at various parts of the body.

These behaviors might be termed "hallucinatory" since no eliciting stimuli could be determined for their occurrence. Motor disturbances, including whole-body shakes, were often present at the same time.

The animals were generally sleepless throughout the drug treatment period.

Reimplantation of amphetamine capsules 2 to 8 months after the first capsule treatment produced the same effects in an individual-specific manner, but the "late phase" behaviors generally appeared sooner. The delayed occurrence of apparent hallucinatory behaviors and other abnormal "late" phase behaviors in the present experiment may be a close parallel to the delayed development of psychosis in humans induced by a similar drug regimen. Furthermore, the hallucinogenic nature of the late amphetamine state is consonant with other reports in the literature that hallucinogen-characteristic behaviors are present at this time.