Psychostimulant abuse

and
Psychosis

Paola Fuentes Claramonte

20484778N
 Psychostimulant abuse and psychosis

Introduction

Chronic use of psychostimulant drugs, like cocaine or amphetamines, has been

reported to produce several damages in the consumer’s health. Psychiatric
problems are a very serious consequence of cocaine abuse which occur
approximately in 75% of chronic consumers, although it is not clear wether
psychopatology is a consequence of drug abuse or was already there when it
started. In fact, individuals who suffer from mental illness seem to be more likely
to become drug abusers.
Long term abuse of cocaine is related to a great number of psychopathologic
problems such as anxiety, irritability, panic attacks, depression, affective
disorders, sexual and eating disorders.
Moreover, there exists evidence that abuse of substances is associated with
greater risk for psychosis in non-psychotic persons. For example, after World
War II, there was a large number of diagnosed psychoses that were developed
following repetitive administration of amphetamine.
The aim of this work is to explore the main characteristics of the psychosis
developed after chronic or long abuse of psychostimulants, and the existing
models that explain how it occurs. I also would like to examine the similarities
and differences of cocaine induced psychosis and those psychotic disorders,
like schizophrenia, that appear without substance consumption.

What is stimulant-induced psychosis?

Psychotic disorders such as schizophrenia are characterised by a list of

symptoms incuding dellusions, hallucinations, disorganised speech and
disorganised behavior. These are considered positive symptoms. They also
include negative symptoms like catatonia and affective flattening. These
symptoms disturb several areas of functioning: work, relationships, self-care...
There are different subtypes of schizophrenia. Many patients can be classified
in one of these: paranoid, catatonic and disorganised type. Generally, the onset
of the disorder occurs in adolescence or early adulthood, but early signals of
schizophrenia can be seen even before. In some cases, however, symptoms
appear without detected predictors after a long period of stimulant drugs abuse.
Then we talk about stimulant-induced psychosis.
Cocaine is one of the stimulant drugs that can induce a psychotic disorder. The
Diagnostic and Statistical Manual of Mental Disorders (DSM - IV) establishes
that a diagnosis of cocaine induced psychosis should be made when psychotic
symptoms are in excess of those typically encountered in intoxication or
withdrawal. Dellusions or hallucinations may appear during these periods, but
their duration and intensity are significantly lower than those provoked by a
psychotic episode. Therefore, stimulant-induced psychosis must be
differentiated from those clinical pictures dominated by delirium and confusion
that appear after acute administration of high doses of stimulants or during
withdrawal.
Paranoid schizophrenia is one of the most frequent disorders among cocaine
abusers. They typically show paranoid and/or grandiosity dellusions.
Hallucinations are often auditory or tactile. Cocaine addicts with psychotic
induced disorder usually show agressive behavior consistent with delirious
ideation. Within an important percentage of patients this pathology persists for
several months and even becomes permanent.
Drug-induced psychosis resembling paranoid schizophrenia can also occur with
repeated or high-dose use of other psychostimulants, like amphetamine and
methanphetamine. Once the psychotic state develops with amphetamine use,
recurrence can happen in response to psychological stressors, without further
use of amphetamine, making the illness difficult to distinguish from
schizophrenia.

Psychosis and behavioral sensitization

It is believed that repetitive administration of stimulant drugs leads to chemical

alterations in the central nervous system, especially affecting the dopaminergic
system. The specific mechanism by which stimulants produce psychosis is not
known, but similarities between behavioral sensitization to stimulants, stimulant-
induced psychosis, and chronic schizophrenia have been proposed.
Behavioral sensitization is the progressive and enduring enhancement of
certain stimulant-induced behaviors that develops following repetitive stimulant
drug administration. We do not have a clear understanding of the underlying
mechanisms of this phenomenon. However, sensitization has been associated
with increased stimulant-induced release of dopamine, which also occurs in
schizophrenic patients without drug consumption. Similarly, past development
of antipsychotic medications was based on their dopamine receptor blocking
properties. One hypothesis to explain sensitization suggests that increased
dopamine release leads to enhanced behavioral response to stimulant
administration. Nevertheless, some researchers have found unchanged or
decreased levels of dopamine release in animals showing behavioral
sensitization after repetitive stimulant administration. Hence, a causal
relationship between change in dopamine release and behavioral sensitization
is not firmly established.
Therefore, although the ability of stimulant drugs to precipitate or exacerbate
psychotic symptoms has been linked to their dopaminergic effects, there are
other neural systems that have also been proposed, like the glutamatergic,
serotonergic and noradrenergic systems, to be linked with stimulant psychosis,
maybe modulating the effects of stimulant drugs on the dopaminergic pathways.
For example, several studies suggest a combined action of dopaminergic and
noradrenergic changes underlying psychotic symptoms. Post’s continuum
model of cocaine psychosis suggests that early euphoric effects may be present
with a high norepinephrine to dopamine ratio, and that this ratio decreases with
continued use, leading to psychotogenic effects.
A hypothesis relating the behavioral sensitization with the genesis of stimulant-
induced psychosis has been proposed. E.H. Ellinwood proposed a gradual
evolution of the symptoms following repetitive stimulant drug abuse. Early in
stimulant administration, the person shows an intense curiosity, which
progresses to intense exploration of the environment if the drug administration
continues over the time. This environmental exploration is displayed in repetitive,
stereotyped searching, sorting and examining behaviors, that could be
characterised as compulsive-like behaviors. Finally, this curious
‘suspiciousness’ of the environment evolves into paranoia and psychotic
thought. The addict may then begin to misinterpret stimuli and often to have
illusions and hallucinations.
When studied on animals, repetitive stimulant administration leads to
sensitization of motor behavior and setereotyped movements. Richtand et al.
pointed that an anallogy can be stablished between this sensitization and that
observed in humans. For example, animals show an increase in stereotyped
grooming behaviors after chronic amphetamine administration. Amphetamine
addicts suffering from amphetamine induced psychosis often spend hours
examining or probing visually accessible parts of the body. Many patients
showing this behavior develop delusions of parasitosis and spend many hours
examining their skin and digging out imagined parasites. These delusions
appear to develop out of early sequences of skin sensations and repetitive
‘grooming responses’. Thus, a parallelism can be drawn between behavioral
sensitization in animals and humans, although we must be conscious about its
limitations since we cannot reproduce the complex cognition of human
psychosis in an animal model.
Nevertheless, following the same pattern of grooming sensitization, thinking
itself could become repetitious. Perception and attention could manifest
sensitization so the subject focuses on minute objects, leading to repetitive
examination and disassembling of electric devices, or to the thinking process
that directs towards the delusion of parasitosis. A sensitization of the attitude of
curiosity and/or suspiciousness that characterizes incipient paranoid
schizophrenia or the beginning phase of amphetamine psychosis, combined
with behavioral disorganization, increasing arousal and/or fear, may evolve into
a paranoid reaction.
The pattern followed by this behavioral evolution can be interpreted as a
sensitization of the exploration behaviors and more complex cognitive
processes. Thus, pathological sensitization of neuronal systems may be an
important factor for the onset or relapse of stimulant-induced psychosis and
schizophrenia. This sensitization would have an endogen basis in psychotic
patients, while stimulant abuse may precipitate it in non-psychotic individuals.
Can stimulant-induced psychosis serve as a model of schizophrenia?

As has been said, there are many similarities between stimulant-induced

psychosis and schizophrenia developed without drug abuse, making it difficult
to differentiate a disorder from the other. This is especially complicated because
schizophrenic individuals tend to abuse drugs, so the origin of the disorder is
not always clear. When psychosis is present, we may ask if latent or actual
schizophrenia is involved.
Due to the similarity of the symptoms, it has been proposed that the underlying
mechanisms causing both disorders may be the same. The sensitization
hypothesis presented above follows this idea. If this was true, then stimulant-
induced psychosis could be a useful model of schizophrenia that would permit
the investigation of its neurobiological basis as well as the cognitive aspects of
the disorder. It would be possible to induce psychosis in animals and study their
brains and behavior. The question is if what happens in an addict’s brain after
repetitive stimulant administration is the same as what happens in the brain of a
schizophrenic without taking drugs.
There are some aspects of both disorders that indicate an important similarity
between them. One of them is that stimulant administration results in
exacerbation of positive symptoms in schizophrenic patients, which is congruent
with the general predominance of positive symptoms reported in stimulant
psychosis. In addition, both disorders are usually treated with the same
antipsychotic medications that attenuate or even eliminate psychotic symptoms.
On the other hand, there are some studies that explore the differences between
substance-induced psychoses and primary psychotic disorders that co-occur
with drug abuse. DSM-IV provides of diagnostic criteria to differentiate the two
conditions. Using them, a longitudinal study in New York found that patients
with substance-induced psychosis showed a later age of the illness onset, as
well as other demographic differencies with the primary psychosis group.
Subjects diagnosed as suffering from primary psychotic disorder had more
severe psychiatric symptoms associated with less insight. The two groups also
showed differences related to hallucinatory behavior (more common in the
substance-induced psychosis group), which maybe reflect differences in the
underlying mechanisms of psychosis. However, this study does not only reffer
to stimulant-induced psychosis, since it included individuals abusing alcohol,
cannabis, cocaine, amphetamines and other drugs. Moreover, it was based on
behavioral data, so we cannot determine biological differences between the two
conditions, which would be very valuable information in the study of substance-
induced psychosis.
Following the sensitization hypothesis, there has been proposed that behavioral
sensitization in animals, due to repetitive stimulant administration, could be a
useful animal model of psychosis (Richtand et al., 2003). However, although it
seems to exist a parallelism between the two processes, behavioral
sensitization and psychosis development, this animal model would have
important limitations. The rodent brain and behavior are more limited than their
human counterpart, and there is no direct correspondence between animal
behavioral sensitization and human psychiatric disease.
Therefore, the question asked before remains unresponsed. Maybe stimulant-
induced psychosis can serve as a model of schizophrenia, but we have to
considerate the limitations of this model since the underlying mechanisms of
these disorders are not clear yet.

Conclusions

I have explored some aspects of stimulant-induced psychosis that I consider

relevant for a better understanding of this disorder. It is clear that substance
abuse can lead to health problems, some of them relating to mental health.
However, it is important to remember that people suffering from mental illness
tend to abuse drugs more than the general population, so the origin of the
disease may be previous to substance use. This is an important aspect to be
considered in diagnosis, since the treatment and prognosis may not be the
same.
An approximation to the mechanisms that can be on the basis of stimulant-
induced psychosis has been proposed as the sensitization hypothesis. But it is
only a hypothesis, which needs to be proved in further investigation. Future
findings in this field may provide a better comprehension of this disorder,
improving the prevention, diagnosis and treatment of these patients.
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