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VOL. 16, NO.

1, 1990
Acute Effects of Drug Abuse
in Schizophrenic Patients:
Clinical Observations and
Patients' Self-Reports
by Lisa Dlxon, Gretchen Haas, Abstract symptoms. Very few data describe
Peter Welden, John Sweeney, the schizophrenic patients' self-

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and Allen Frances Substance abuse among schizo- reported reasons for drug use and
phrenic patients is an increasingly their subjective experience of the in-
recognized clinical phenomenon. toxicated state. The focus on how
The authors review experimental drug use affects psychotic symptoms
and observed clinical effects of drug may have resulted in neglect of
abuse and patients' subjective ex- other significant drug effects—for ex-
periences of acute intoxication. ample, on depression, anxiety, and
Though drug abuse may exacerbate negative symptoms. Attention to the
psychotic symptoms, abused drugs heterogeneity of drug effects across
may also lead to transient symptom different patient groups, different
reduction in subgroups of schizo- drugs, and different symptoms may
phrenic patients. Some patients offer insight into the reasons
report feeling less dysphoric, less underlying the abuse of drugs by
anxious, and more energetic while schizophrenic patients. While a
intoxicated. Models of the relation- number of models previously of-
ship of drug abuse and schizophre- fered to explain the interaction of
nia, particularly the self-medication drug abuse and schizophrenia have
hypothesis, are discussed in merit, the application of these data
reference to these data. to the self-medication hypothesis of-
fers an important perspective,
especially when considering schizo-
The comorbidity of schizophrenia phrenic patients' apparent drug
and substance abuse is well docu- preferences.
mented, with up to 60 percent of
schizophrenic patients being
reported to use or abuse illicit drugs Acute Drug Effects
(Alterman et al. 1980; Richard et al.
1985; Negrete et al. 1986; Dixon et The majority of reports in the
al. 1989a; Miller and Tanenbaum literature indicate that abused drugs
1989; and Dixon et al., submitted for generally cause an acute worsening
publication). The lack of outpatient of psychotic symptoms in schizo-
treatment programs which treat phrenia. However^ a significant
dual-diagnosis patients has com- heterogeneity of response has been
pounded this problem (GottheU and observed in the empirical investiga-
Weinstein 1980; Solomon 1986). If tions of acute drug effects, and
rational treatment strategies are to careful examination of the data sug-
be designed, it is necessary to gests that abused drugs may pro-
develop empirical and theoretical duce possible benefits as well as
foundations to understand why adverse effects. Data on drug effects
schizophrenic patients abuse come from the following three
psychoactive drugs. general sources: (1) experimental
To date, experimental studies have observation, (2) clinical reports, and
examined the acute effects of
psychoactive drugs on the psy-
chopathlogy of schizophrenic pa- Reprint requests should be sent to Dr.
tients. Clinical observations of drug- L. Dixon, Maryland Psychiatric Research
abusing patients have focused on Center, P.O. Box 21247, Baltimore, MD
the impact of drugs on psychotic 21228.

(3) retrospective studies of patient amphetamine caused no effects or generally focused on the co-
groups (primarily inpatient). even improvements in negative occurrence of psychotic symptoms

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symptoms (Kornetsky 1977; Angrist and relapse with substance abuse.
Experimental Studies. Experimental et al. 1982; van Kammen et al. 1982; Unfortunately, these reports have
observations of schizophrenic pa- Cesarec and Nyman 1985). Opiates very rarely used systematic assess-
tients under the influence of drugs and opiatelike peptides, endorphins, ment procedures and standardized
have been reported primarily for have been reported to have anti- scales. Treffert (1978) and Knudsen
hallucinogens, phencyclidine (PCP), psychotic properties (Comfort 1977; and Vilmar (1984) reported exacerba-
amphetamines, benzodiazepines, Gold et al. 1977), although clinical tion of psychosis in small samples of
and opiates. Experimental studies trials of opiates have, as with am- schizophrenic patients who use can-
from the 195Cs and 196CKS in which phetamines, yielded inconsistent nabis. Negrete et al. (1986) evaluated
schizophrenic patients were given results with moderate overall im- 137 schizophrenic outpatients and
hallucinogenic drugs showed that provements (Berger et al. 1980), found that cannabis users had sig-
most subjects in these studies ex- reduction of psychotic symptoms nificantly more delusional and
(Brizer et al. 1985), and worsening of hallucinatory activity than nonusers.
hibited exacerbation of anxiety and
negative symptoms (Judd et al. Heavy cannabis users showed the
psychosis, but a minority of subjects
1981). Opioid antagonists have also most symptomatology. Bernhardson
experienced euphoria and relaxation
been reported to reduce psychotic and Gunne (1972) found that in 7 of
or were not affected (Hoch 1951;
symptoms (Gunne et al. 1977), but the 14 patients whose psychosis
Hoch et al. 1952; Pennes 1954). predated cannabis use, cannabis
this finding is again inconsistent
Ellinwood and Fetrie (1979) com- (Davis et al. 1977). Benzodiazepines abuse produced a further psychotic
mented that these drug effects were have been found to worsen psy- deterioration; cannabis did not
similar to the acute disorganizing ef- chotic symptoms and produce in- appear to exert any effect on the
fects of schizophrenia, and they tolerable side effects in some remaining 7 patients. Hekimian and
noted that the chronic patient may patients (Dixon et al. 1989b), but also Gershon (1968) evaluated 112 pa-
be less vulnerable to the psycho- appear to reduce anxiety, positive tients who had abused drugs within
tomimetic drug effects of hallucino- symptoms, and negative symptoms 48 hours of their admission to
gens. Fink et al. (1966) administered (Jimerson et al. 1982; Csernansky et Bellevue Hospital (of whom 39 per-
varying doses of lysergic acid diethy- al. 1984; Kahn et al. 1988; Wolkowitz cent had a predrug diagnosis of
lamide (LSD) to 65 psychotic sub- et al. 1988; Douyon et al. 1989) in schizophrenia). Although the find-
jects and found only a 2 percent in- subgroups of schizophrenic patients. ings were given by drug rather than
cidence of prolonged psychotic ex- Moreover, benzodiazepines are now by psychiatric diagnosis, Hekimian
acerbations characterized by an in- commonly used in the treatment of and Gershon reported that all drugs
itial irritable period followed by neuroleptic-induced akathisia. Thus, increased psychosis or psychopath-
thought disorder, visual hallucina- almost all drugs tested have the ology for the large majority of users.
tions, and elevated mood. PCP in- potential to exacerbate psychosis— Alterman et al. (1980) reported that
creased psychotic symptoms and psychostimulants and hallucinogens schizophrenic inpatients who abus-
agitation in most schizophrenic pa- more so than benzodiazepines. ed alcohol while in the hospital had
tients in whom it was tested, similar Opiates alone have not consistently unspecified changes in sleeping pat-
to an acute exacerbation of their been demonstrated to worsen terns, mood, and behavior. Alter-
underlying illness (Luby et al. 1959; psychosis. However, reductions of man et al. (1982) also reported that a
Levy et al. 1960). depression, anxiety, and negative cohort of drug-abusing hospitalized
symptoms also have been observed inpatients, 80 percent of whom were
While even small doses of in subgroups of schizophrenic pa- schizophrenic, had more mood
stimulant drugs like the am- tients experimentally medicated changes than nondrug abusers but
phetamines are known to induce with classically abused drugs. demonstrated the same degree of
psychosis and to worsen symptoms depression, paranoia, delusions,
(Janowsky et al. 1973; West 1974; and hallucinations. Several reports
Janowsky and Davis 1976; Angrist et Clinical Reports and Epidemiologic have found increased hospitaliza-
al. 1980), this effect is not uniform, Surveys. Clinical studies of drug- tions among schizophrenic drug
and some authors have found that abusing schizophrenic patients have
VOL. 16, NO. 1, 1990 71

abusers (Craig et al. 1985; Richard et schizophrenic patients reported that gressive," or "splitting of thoughts."
al. 1985; Rader et al. 1988). alcohol reduced discomfort caused Subjective effects of other drugs in

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by hallucinations. Hansell and Willis groups of schizophrenic patients
Critique/Summary. Interpretation of (1977) also found that patients have been less commonly reported.
the above sources of data on drug reported symptom reduction with Judd et al. (1981) administered the
effects in schizophrenia must take alcohol. In contrast, Kesselman et al. Profile of Mood States (McNair et al.
into account certain specific limita- (1982) reported that 75 percent of 1971) to six schizophrenic patients
tions. Data from laboratory studies patients who commented had felt undergoing drug challenge with
should be interpreted with caution that alcohol worsened their methadone. Self-ratings by patients
"schizophrenic" symptoms. indicated significant increases of
because experimental paradigms to
test drug effects may not duplicate Cannabis has also generated a depression-dejection and fatigue
the environment, or the type, dose, varied response. Weil (1970) review- with methadone. The majority of
and purity of drugs schizophrenic ed adverse reactions to cannabis and Hekimian and Gershon's (1968)
patients encounter when abusing reported that many schizophrenic groups of amphetamine users and
patients found marijuana unpleas- hallucinogen users had schizophre-
drugs outside of the laboratory. Fur-
ant with frequent feelings of "de- nia, and they reported favorable and
thermore, clinical observations of
realization." Negrete et al. (1986) unfavorable subjective experiences
drug-abusing schizophrenic inpa- found that schizophrenic subjects
tients are likely to overrepresent ex- for each drug, respectively.
who reported previous cannabis ex-
acerbations and underrepresent In a study of 83 consecutively ad-
perience tended to stop this practice
benefits, since the study population mitted DSM-III-R (American
more readily than nonschizophrenic
is a relapsing one, and adverse ef- Psychiatric Association 1987)
users. They speculated that this
fects are more likely to come to clini- tendency might be due to a high fre- schizophrenic (n - 65), schizoaffec-
cians' attention. quency of untoward reactions; all tive (n = 12), and schizophreniform
Despite these difficulties, the except 7 of the 76 subjects in their (n = 3) inpatients, Dixon and col-
evidence is compelling that a wide sample reported adverse psychic leagues asked 40 patients who also
range of drugs are associated with effects, although these effects are met criteria for a lifetime diagnosis
exacerbation of psychotic symptoms not defined specifically. In contrast, of DSM-III-R drug or alcohol abuse
in many patients. However, there are Hekimian and Gershon (1968) or dependence (Dixon et al. 1988,
reported that in their sample of 1989) to indicate the direction in
two important qualifications to this
eight cannabis users, of whom six which selected symptoms and af-
observation: (1) drug response is
had a predrug and postdrug diag- fects changed during acute drug in-
heterogeneous among schizophrenic
nosis of schizophrenia, five reported toxication (i.e., drug-abusing pa-
patients (e.g., across acute vs.
a "favorable subjective response" to tients were asked to say whether
chronic, anxious vs. nonanxious,
cannabis. Knudsen and Vilmar cannabis acutely increased, de-
and other subgroups); (2) not all creased, or produced no effect on
drugs have a pathological effect on (1984) presented descriptions of 10
schizophrenic patients medicated anxiety). Alcohol, cannabis, and co-
specific symptoms (e.g., ampheta- caine were the drugs abused com-
with neuroleptics of whom 7, they
mines, opiates, and benzodiaze- monly enough for meaningful
contended, used cannabis to reverse
pines). Patients' self-reports also neurolepric effects. For example, one results to be obtained. The large
reflect this heterogeneity. patient reported that cannabis allow- majority of substance-abusing pa-
ed her to "regain experiences blotted tients felt that all three drugs
Drug Effects Reported by out by medication." Knudsen and decreased depression (table 1). In
Schizophrenic Patients Vilmar described patients' experi- contrast, reported effects on anxiety,
ences with cannabis in detail; energy, and psychotic symptoms dif-
responses were characterized by an fered for the three drugs. For exam-
Clinical Reports. Reports of initial feeling of being "inspired," ple, drug-abusing patients reported
schizophrenic patients' subjective "relaxed," "energized," or "active," that cannabis and alcohol decreased
responses to drugs have been largely followed by an exacerbation of anxiety but that cocaine made them
anecdotal and often vague. Alpert symptoms and feeling "bad," "ag- more anxious.
and Silvers (1970) found that some

Table 1. Schizophrenic patients' subjective report of acute drug them. The patients' particular
effects drug(s) of choice had already been

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identified in the interview and were
Alcohol Cannabls Cocaine
substituted into the statement. In
contrast to data on subjective effects,
Anxiety lit • • • t t
no drug differences appeared in pa-
Depression • » » I t t I l tients' responses to reasons for drug
Calm t t t t t t * use.
Suspiciousness t t t «•» *
Almost 75 percent of patients
Trust t «•» «-» * • •
acknowledged that they used drugs
Hallucinations t m t m »
"to get high" and "to relax." In
Energy « « t t • t t t
about half of the cases, patients also
Note, t Indicates Increase. • Indicates decrease. • • Indicates no change. Different arrows within endorsed the responses that were
same category indicate mixed response. probing for the desire for negative
symptom relief— "to increase
pleasure," "to increase energy," "to
Critique /Summary. The method of reasons that schizophrenic patients increase emotions," and "to talk
obtaining posthoc reports of subjec- abuse drugs. In Hekimian and Ger- more." These statements, of course,
tive drug effects has many limita- shon's (1968) study of 112 patients might not necessarily apply ex-
tions. It relies on patients' memories who had used drugs within 48 clusively to negative symptoms and
of feelings and experiences while in- hours of hospital admission, the could represent efforts to reduce
toxicated (state-dependent recall). It desire for euphoria (which included symptoms of depression. Approx-
is subject to reporting biases of recall the desire to "get high" or "relieve imately half of the patients also en-
and more general problems of unre- depression") was most important for dorsed the statement, "I use [drug]
liability. Moreover, a self-report heroin, amphetamines, and hallu- to go along with the group," sug-
assessment of motivation for drug cinogens, while the influence of gesting that social pressures play an
use and drug effects may be largely friends or environment was most important role for certain patients
based on posthoc rationalizations of important for marijuana. The across all drugs. Patients infrequent-
impulsive acts or acts driven by majority of amphetamine, hallucino- ly acknowledged the use of drugs to
other factors. Nevertheless, the gen, and marijuana users had increase concentration, to help
individuals' perceptions of drug schizophrenia. Three of the 10 pa- them work better, and to relieve
effects may be integral to the tients described by Knudsen and neuroleptic-induced side effects, and
development or maintenance of Vilmar (1984) stated that they used psychotic symptoms.
drug-seeking behavior. While the cannabis for the social contacts and
data are limited, subgroups of pa- "Bohemian lifestyle" surrounding Critique/Summary. These data are
tients dearly report feeling less cannabis use. Two patients describ- limited as are the data on reported
depressed, less anxious, and, in ed by Treffert (1978) smoked can- subjective effects above; self-
some cases, more energized while nabis to decrease depression and to reported reasons for drug use are
intoxicated, in spite of frequent improve social relationships. biased, without proven reliability,
awareness of the psychotogenic In our study (Dixon et al. 1989a; and could be posthoc rationaliza-
potential of drugs they abuse. Dixon et al., submitted for publica- tions rather than accurate represen-
tion), patients were read a series of tations of subjects' intent and
statements, such as "I use [drug] to motivations. Nevertheless, they do
Self-Reported Reasons for relieve anxiety" or "I use [drug] to suggest that dysphoria, anxiety,
Drug Use increase my number of thoughts," desire for socialization, and possibly
and were asked to respond, "yes," the anergia associated with negative
There is a remarkable paucity of "no," or "uncertain," depending on symptoms may impel schizophrenic
studies describing the self-perceived whether the statement was true for patients to abuse drugs.
VOL. 16, NO. 1, 1990 73

Situational Factors phrenia; schizophrenic patients Bowers 1987). This model derived
abuse drugs which can increase from early experimental observa-

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With the exception of Hekimian and psychosis, but from which some pa- tions of the psychotogenic proper-
Gershon's (1968) observations on the tients apparently derive beneficial ties of many drugs, and it has
social and environmental factors effects. These data are discussed in received support from the finding of
associated with the use of mari- the context of models that have been McClellan et al. (1979) that am-
juana, there is a dearth of informa- advanced to understand the interac- phetamine users were significantly
tion about the specific circumstances tion of drug abuse and schizophre- more likely to develop psychotic
or external stimulus/reinforcement nia. It is important to note that the disorders than were barbiturate
conditions associated with drug use discussion focuses only on how the abusers. Andreasen et al. (1987)
among schizophrenic patients. In psychological and subjective data reviewed the records of 45,570
our study, we asked patients where presented can be informative in Swedish conscripts and found that
and with whom they used their generating hypotheses to under- the relative risk of schizophrenia
preferred drugs. Over half of the pa- stand the interaction of drug abuse among high consumers of cannabis
tients reported using drugs alone at and schizophrenia. Other ap- was 6.0 times that of nonusers. They
least some of the time. Patients proaches to the problem of co- concluded that cannabis use is an
seemed as likely to use drugs on the morbidity (e.g., biological or behav- independent risk factor in the
street or in a public place as at home ioral) may be equally valid and development of schizophrenia,
(table 2). informative. although documentation of subjects'
early functioning has been ques-
tioned. Studies reporting that drug-
Discussion Etiological Model. Drug abuse has abusing schizophrenic patients have
been hypothesized to be an an earlier age of onset of illness
These data illustrate a core clinical etiological factor in a subgroup of (Breakey et al. 1974; Tsuang et al.
problem of drug abuse in schizo- patients with schizophrenia (e.g., 1982; Alterman et al. 1984; Weller et
al. 1988) and better premorbid func-
tioning (Breakey et al. 1974; Tsuang
Table 2. Where and with whom schizophrenic patients used drugs et al. 1982) than schizophrenic pa-
tients who do not abuse drugs have
Alcohol (%) Cannabls (%) Cocaine (%) Total (%) been used to support the hypothesis
that drug abuse played a role in the
With whom do you onset of schizophrenia. Finally, the
use [drug]? observation that schizophrenic pa-
Always alone 28 32 7 25 tients may preferentially abuse
Usually alone 17 8 7 11 substances that induce psychosis
As likely to be alone (Schneier and Siris 1987; Weller et
as not 33 12 27 28 al. 1988) may support this model.
Usually with other Cross-sectional data on observed
people 22 32 27 28 or subjective response to drug abuse
Always with other are subject to systematic biases and
people 0 12 33 14 do not allow critical assessment of
Where do you the etiological model. Without pro-
usually use [drug]? spective controlled studies, conclu-
sions about drug abuse as an
On the street or etiological factor in schizophrenia
a public place 42 37 43 40 are largely inferential.
At home 47 42 29 40
At a friend's home 0 4 14 5
Dopamine Dysfunction Model.
At school or work 8 0 4
Other 11 8 14 11
Evidence of the involvement of the
dopamine system in reinforcement

and reward function (Prosser and self-medicate depression (Freed to support the notions that (1) the
Pickens 1979; Ritz et al. 1987), com- 1975; Siris et al. 1988), negative drugs abused by schizophrenic pa-

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bined with the large body of indirect symptoms (Schneier and Siris 1987), tients may diminish other symptoms
evidence implicating dopamine in or neuroleptic-induced extrapyrami- such as dysphoria, anxiety, and
schizophrenia (Snyder 1976), has led dal side effects (Treffert 1978; anergia; and (2) that patients believe
to suggestions that dopamine dis- Knudsen and Vilmar 1984) with that drugs diminish such symptoms.
turbances may heighten vulnerabili- drugs. The self-medication model Experimental studies indicated
ty to both schizophrenia and drug has been advanced to explain drug that some stimulant drugs produced
abuse in some patients (Prosser and use not only in schizophrenia, but improved functioning and reduced
Pickens 1979). This model is largely also in the general population symptoms in some patients, and in-
theoretical without direct clinical or (Khantzian 1985). terestingly, schizophrenic patients
experimental evidence to support it The self-medication model has a may preferentially abuse stimulants
at this point. biochemical logic in that schizo- (Schneier and Siris 1987). Opiates
phrenic patients may prefer drugs and benzodiazepines have also been
with dopaminergic action (Schneier found to exhibit antipsychotic as
Socializing Effects Model. Drug use
and Siris 1987) which have the well as anxiolytic and antidepressant
by schizophrenic patients may be a
potential to reverse neuroleptic- qualities in patients with schizo-
socializing phenomenon, providing
induced extrapyramidal side effects. phrenia. The suggestion that
isolated, socially handicapped in-
Moreover, if negative symptoms are schizophrenic patients may use
dividuals with an identity and a opiates and benzodiazepines less
due to dopamine hypoactivity as
social group (Treffert 1978; Hall et al. than other populations (Schneier
suggested by Weinberger (1987) and
1979; Millman and Sbriglio 1986). and Siris 1987) warrants discussion.
Friedhoff (1983), then the self-
Schizophrenic patients in the Drugs with antipsychotic properties
medication hypothesis is even more
samples of Hekimian and Gershon might mask psychotic symptoms so
compelling from a neurochemical
(1968) and Knudsen and Vilmar point of view, since abused drugs that patients would receive relatively
(1984) used marijuana and hal- with dopaminergic function may less clinical attention. Such patients
lucinogens for social contacts and reverse this purported dopamine might also receive treatment in
because of the "influence of deficit in the same way, perhaps, methadone clinics with a primary
friends." In our sample, approx- that the decreased brain dopamine focus on drug abuse rather than
imately half of the patients reported levels associated with chronic co- schizophrenia. These factors would
using drugs to "go along with the caine use may help to maintain co- make schizophrenic opiate and ben-
group," suggesting that social factors caine addiction (Wyatt et al. 1988). zodiazepine abusers relatively less
are operative, for at least some pa- Thus, although the remainder of the visible in the traditional hospital and
tients, across all drugs. However, discussion focuses on psychological community settings where schizo-
this explanation does not hold for all factors, there may also be parallel or phrenic patients receive care. Alter-
drug use. A large number of pa- complementary biological deter- natively, schizophrenic patients may
tients did not endorse the socializa- minants driving the "self- in fact use opiate drugs less fre-
tion item in our sample, and a medication." quently than other populations for
substantial portion of patients used various reasons—for example, if
drugs unaccompanied by others. The actions of drugs may allow in- opiates are too difficult for schizo-
The abundance of solitary drug use ferences about motivations for drug- phrenic patients to obtain, if the
seeking behavior. To that end, the depressant effects reported by Judd
argues against drug abuse as a pure-
most striking aspect of the literature et al. (1981) generalize to other pa-
ly socializing phenomenon. More
review on drug effects is how com- tients, or if schizophrenic patients
research on the setting and cir-
monly the abuse of drugs induced intend to increase, not to reduce,
cumstances of drug use by schizo-
psychotic exacerbations in schizo- psychosis with drug abuse.
phrenic patients is necessary to phrenic patients. Is psychosis just an
evaluate this model. unwanted side effect of illicit drug The subjective response of schizo-
use, or an intended effect? We have phrenic patients to drug abuse sug-
Self-Medication Model. Drug- no data to answer that question ade- gests that they may perceive them-
abusing schizophrenic patients may quately. However, data are available selves as self-medicating symptoms.
VOL. 16, NO. 1, 1990 75

In our sample, schizophrenic drug withdrawn schizophrenic patient). classically abused drugs. Moreover,
abusers reported an overall subjec- Significant motivation and activity many patients report feeling less

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tive antidepressant effect common to are required to sustain drug- depressed, less anxious, and more
the three most popularly abused seeking/drug-using behavior. energized with their drug of choice,
drugs—cannabis, cocaine, and Indeed, Andreasen (1982) found and they report using drugs for that
alcohol—and attributed differential that schizophrenic patients with reason. Treatments with anxiolytic
anxiolytic, activating and psycho- negative symptoms as measured by agents or antidepressants, as well as
togenic effects to each, perhaps the Scale for the Assessment of reductions in neuroleptic dosage,
using the drugs in patterns specific Negative Symptoms were less likely might be logical corollaries to these
to their symptomatology. Thus, a to have histories of drug abuse than data.
way of understanding the popularity were patients with positive symp-
of cannabis abuse is that cannabis, toms. Perhaps there is a "critical Independence Model. Finally, it has
in addition to its reported acute anti- window" for the propensity to self- been postulated that determinants of
depressant effects (common to medicate; patients with too few, or drug abuse in schizophrenia may
cocaine and alcohol), was perceived too many, negative symptoms may not differ from those in the general
to have desirable anxiolytic and ac- not effectively seek or maintain a population. Historically, explana-
tivating effects. drug-use habit. tions of drug abuse have included,
Patients' reasons for drug use An alternative explanation is that among others, the desire for
apply directly to the self-medication dysphoria may be the final common euphoria and escape (Khantzian
model. Almost all reports in the pathway to drug abuse. Perhaps on- 1985); sociodemographic factors
literature indicated that patients ly those patients whose symptoms such as poverty, age, and sex (Falk
reported using drugs to relieve (positive, negative, or extrapyram- and Feingold 1987); familial and
dysphoria and to feel more relaxed. idal) lead to distress or depression genetic factors (Cadoret et al. 1986);
In our study, many of the responses are the ones who abuse drugs. Siris and self-medication (Kolb 1962;
were consistent with a desire for et al. (1988) reported that in a sam- Khantzian 1985). The schizophrenic
relief of negative symptoms. Fewer ple of patients with postpsychotic patients' stated reasons for drug use
patients reported "medicating" depression (from which active drug and descriptions of drug effects are
themselves to affect extrapyramidal users were excluded), patients with similar to those reported in non-
side effects, but it is often difficult a history of drug abuse had more schizophrenic subjects (Fischman et
for patients (and clinicians) to deter- features of endogenous depression, al. 1976). The self-medication and
mine the etiology of symptoms; for suggesting that previous drug socialization models may apply to
example, a patient might not recog- abusers had been self-medicating schizophrenic patients no differently
nize that neuroleptics cause the depression. Dysphoria secondary to than to other populations. Even if
"depression" or listlessness that they neuroleptics or negative symptoms that is so, it seems inescapable that
acknowledge self-medicating. might escape measurement by stan- the targets of self-medication are at
The application of the self- dard instruments designed for en- least partially determined by schizo-
medication model to substance dogenous depression. Investigation phrenic symptomatology (or effects
abuse in schizophrenia must be of this hypothesis would thus of neuroleptic treatment). In addi-
examined in light of the severity and benefit from increased sophistication tion, the apparent preference of
nature of the impairments in schizo- in methodologies designed to evalu- schizophrenic patients for psycho-
phrenia. For example, although ate schizophrenic patients' subjec- tomimetic agents (Schneier and Siris
evidence may suggest that schizo- tive experience of their illness, 1987), consistent with our data
phrenic patients self-medicate symptoms, and treatments. (Dixon et al. 1989a; Dixon et al. sub-
negative symptoms, negative symp- mitted for publication), suggests
Despite all the questions raised, some selective matching of
toms presumably diminish the the self-medication model appears
patients' capacities to seek and psychotomimetic agents with
to have heuristic value for further schizophrenia.
obtain drugs. Thus, patients with research on drug abuse among
the most severe negative symptoms schizophrenic patients. Subgroups Factors independent of schizo-
would be unlikely to abuse drugs of schizophrenic patients improve phrenia undoubtedly play an impor-
(e.g., a profoundly apathetic, with experimental administration of tant role in determining which

schizophrenic patients become drug schizophrenic patients find alter- negative and positive symptoms in
abusers. At a very basic level, drug native ways to cope with dysphoria schizophrenia. Psychopharmacology,

Downloaded from http://schizophreniabulletin.oxfordjournals.org/ at Purdue University Libraries ADMN on June 17, 2015
exposure is required. The question as well as the consideration of phar- 72:17-19, 1980.
may not be whether independent macological treatments. Angrist, B.; Peselow, E.; Rubinstein,
factors are involved but, rather, to M.; Corwin, ].; and Rotrosen, ]. Par-
what extent factors specific to tial improvement in negative schizo-
schizophrenia determine drug References
phrenic symptoms after ampheta-
abuse. To answer this question will mine. Psychopharmacology,
Alpert, M., and Silvers, K.N.
require controlled studies that com- 78:128-130, 1982.
Perceptual characteristics
pare schizophrenic patients to other
distinguishing auditory hallucina- Berger, P.A.; Watson, S.J.; and Akil,
groups of psychiatric patients and
tions in schizophrenia and acute H. Beta-endorphin and schizophre-
drug abusers.
alcoholic psychoses. American Journal nia. Archives of General Psychiatry,
of Psychiatry, 127:298-302, 1970. 37:642-647, 1980.
Conclusion Alterman, A.J.; Ayre, R.R.; and Bernhardson, G.; and Gunne, L.E.
Williford, W.O. Diagnostic validation Forty-six cases of psychosis in can-
The answer to the question of which of conjoint schizophrenia and
schizophrenic patients abuse drugs nabis users. International Journal of
alcoholism. Journal of Clinical Addiction, 7:9-16, 1972.
and why may lie in a combination of Psychiatry, 45:300-303, 1984.
models. A schizophrenic patient Bowers, M.B., Jr. The role of drugs
who has a family history of drug Alterman, A.J.; Erdlen, D.L.; in the production of schizophreni-
abuse, is exposed to drugs, and has Laporte, D.J.; and Erdlen, F.R. Prob- form psychoses and related
little impairment of affect and only lem drinking in hospitalized schizo- disorders. In: Meltzer, H.Y., ed.
mild negative symptoms may be at phrenic patients. Addictive Behaxnor, Psychopharmacology: The Third
highest risk for substance abuse. 5:273-276, 1980. Generation of Progress. New York:
While the role of substance abuse in Alterman, A.J.; Erdlen, D.L.; Raven Press, 1987. pp. 819-823.
the pathogenesis of schizophrenia is Laporte, D.J.; and Erdlen, F.R. Ef- Breakey, W.R.; Goodell, H.; Lorenz,
not well understood, the available fects of illicit drug use in an in- P.C.; and McHugh, P.R. Hallucino-
evidence linking substance abuse patient psychiatric population. Ad- genic drugs as precipitants of
with the onset of the disorder dictive Behavior, 7:231-242, 1982. schizophrenia. Psychological Medicine,
should be taken as an important American Psychiatric Association. 4:255-261, 1974.
public health warning for in- DSM-III-R: Diagnostic and Statistical
dividuals at high risk for schizophre- Brizer, D.A.; Hartmen, N.; Sweeney,
Manual of Mental Disorders. 3rd ed., J.; and Millman, R.B. Effect of
nia to avoid psychotomimetic agents. revised. Washington, DC: The
Application of the self-medication methadone plus neuroleptics on
Association, 1987. treatment-resistant chronic paranoid
hypothesis to the subjective
responses of schizophrenic patients Andreasen, N.C. Negative symp- schizophrenics. American Journal of
to drug abuse suggests the need for toms in schizophrenia: Definition Psychiatry, 142:1106-1107, 1985.
increased clinical sensitivity to ex- and reliability. Archives of General Cadoret, R.J.; Troughton, E.;
periences of anxiety and depression, Psychiatry, 39:784-788, 1982. O'Gorman, T.W.; and Heywood, E.
whether they are primary, Andreasson, S.; Engstrom, A.; An adoption study of genetic and
neuroleptic-induced, or a conse- Allebeck, P.; and Rydeberg, U. Can- environmental factors in drug abuse.
quence of coping with a disabling, nabis and schizophrenia: A longi- Archives of General Psychiatry,
stigmatizing, and isolating illness. tudinal study of Swedish conscripts. 43:1131-1136, 1986.
Treatment implications derived from Lancet, 0:1483-1486, 1987. Cesarec, Z., and Nyman, A.K. Dif-
the self-medication model include Angrist, B.; Rotrosen, J.; and ferential response to amphetamine
the need to develop cognitive and Gershon, S. Differential effects of in schizophrenia. Acta Psychiatrica
rehabilitative strategies to help amphetamine and neuroleptics on Scandinavica, 71:523-528, 1985.
VOL. 16, NO. 1, 1990 77

Comfort, A. Morphine as an an- E.; Cooper, T.; and Rotrosen, J. and perceived psychiatric problems
tipyschotic. Clinical Toxicology, Neuroleptic augmentation with in alcoholism services. In: Gottheil,

Downloaded from http://schizophreniabulletin.oxfordjournals.org/ at Purdue University Libraries ADMN on June 17, 2015
11:383-386, 1977. alprazolam: Clinical effects and E.; McClellan, A.T.; and Druley,
Craig, T.J.; Lin, S.P.; O-Defrawi, pharmacokinetic correlates. American K.A., eds. Substance Abuse and
M.H.; and Goodman, A.B. Clinical Journal of Psychiatry, 146:231-234, Psychiatric Illness. Elmsford, NY:
correlates of readmission in a 1989. Pergamon Press, 1980.
schizophrenic cohort. Psychiatric Ellinwood, E.H.; and Petrie, W.M. Gunne, L.M.; Lindstrom, L.; and
Quarterly, 57:5-10, 1985. Drug-induced psychoses. In: Terenius, L. Naloxone-induced
Csernansky, J.G.; Lombrozo, L.; Pickens, R.W., and Heston, L.L., reversal of schizophrenic hallucina-
Gulevich, G.; and Hollister, L. Treat- eds. Psychiatric Factors in Drug Abuse. tions. Journal of Neural Transmission,
ment of negative schizophrenic New York: Grune and Stratton, 40:13-19, 1977.
symptoms with alprazolam: A pre- 1979. pp. 301-336. Hall, R.; Stickney, S.K.; Gardner,
liminary open-label study. Journal of Falk, J.L., and Feingold, D.A. En- E.R.; Perl, M.; and LeCann, A.F.
Clinical Psychopharmacology, vironmental and cultural factors in Relationship of psychiatric illness to
4:349-352, 1984. the behavioral actions of drugs. In: drug abuse. Journal of Psychedelic
Davis, G.C.; Bunney, W.E., Jr.; Meltzer, H.Y., ed. Psychophar- Drugs, 11:337-342, 1979.
DeFraites, E.G.; Kleinman, J.E.; van macology: The Third Generation of Hansell, N.; and Willis, G.L. Out-
Kammen, D.P.; Post, R.M.; and Progress. New York: Raven Press, patient treatment of schizophrenia.
Wyatt, R.J. Intravenous naloxone ad- 1987. pp. 1503-1510. American Journal of Psychiatry,
ministration in schizophrenia and Fink, M.; Simeon, J.; Haque, W; 134:1082-1086, 1977.
affective illness. Science, 197:74-77, and Itil, T. Prolonged adverse reac- Hekimian, L.J., and Gershon, S.
1977. tions to LSD in psychotic subjects. Characteristics of drug abusers ad-
Dixon, L.; Haas, G.H.; Dulit, R.A.; Archives of General Psychiatry, mitted to a psychiatric hospital. Jour-
Weiden, P.J.; Sweeney, J.; and Hien, 15:450-454, 1966. nal of the American Medical Associa-
D. Substance abuse in schizophre- Fischman, M.W.; Resnekov, L.; tion, 205:125-130, 1968.
nia: Preferences, predictors and Schick, J.F.E.; Krasnegor, N.A.; Hoch, D.H. Experimentally pro-
psychopathology. Schizophrenia Fennel, W.; and Freedman, D.X. duced psychoses. American Journal of
Research, 2:6, 1989a. Cardiovascular and subjective effects Psychiatry, 107:607-611, 1951.
Dixon, L.; Haas, G.H.; Weiden, P.J.; of intravenous cocaine administra- Hoch, P.H.; Cattell, J.P.; and Pen-
Sweeney, J.; and Frances, A.J. tion in humans. Archives of General nes, H.H. Effects of mescaline and
"Schizophrenia and Drug Abuse: Psychiatry, 33:983-989, 1976. lysergic acid (e-LSD-25). American
Who, What, and W h y r Presented Freed, E.X. Alcoholism and schizo- Journal of Psychiatry, 108:579-584,
at the Annual Meeting of the phrenia: The search for perspec- 1952.
American Psychiatric Association, tives—A review. Journal of Studies on Janowsky, D.S., and Davis, J.M.
San Francisco, CA, May 1988. Alcohol, 36:853-881, 1975. Methylphenidate, dextroampheta-
Dixon, L.; Haas, G.H.; Weiden, P.J.; Friedhoff, A.J. A strategy for mine, and levamfetamine: Effects of
Sweeney, J.; and Frances, A.J. "Drug developing novel drugs for the treat- schizophrenic symptoms. Archives of
Abuse in Schizophrenia: Clinical ment of schizophrenia. Schizophrenia General Psychiatry, 33:304-308, 1976.
Correlates and Reasons for Use." Bulletin, 9:555-562, 1983. Janowsky, D.S.; El-Yousef, M.K.;
Submitted for publication. Gold, M.S.; Donabedian, R.K.; Davis, J.M.; and Sekerke, H.J. Pro-
Dixon, L.; Weiden, P.J.; Frances, Dillard, M.; Slobetz, F.W.; Riordan, vocation of schizophrenic symptoms
A.J.; and Sweeney, J. Alprazolam in- C.E.; and Kleber, H.D. Antipsy- by IV administration of methyl-
tolerance in stable schizophrenic chotic effect of opiate agonists. phenidate. Archives of General
outpatients. Psychopharmacology Lancet, 11:398-399, 1977. Psychiatry, 28:185-191, 1973.
Bulletin, 25:213-214, 1989b. Gottheil, E., and Weinstein, S.P. Jimerson, D.C.; van Kammen, D.P.;
Douyon, R.; Angrist, B.; Peselow, Staffing patterns, treatment setting, Post, R.M.; Docherty, J.P.; and

Bunney, W.E., Jr. Diazepam in Luby, E.D.; Cohen, B.D.; Rosen- CM.; Kashner, T.M.; Buchanon, S.;
schizophrenia: A preliminary baum, G.; Gottlieb, J.S.; and Kelly, and Westerdorp, F. Hospital utiliza-

Downloaded from http://schizophreniabulletin.oxfordjournals.org/ at Purdue University Libraries ADMN on June 17, 2015
double-blind trial. American Journal of R. Study of a new schizophreno- tion in schizophrenia. New Research
Psychiatry, 139:489-491, 1982. mimetic drug Semyl. Archives of Programs and Abstracts, American
Judd, L.L.; Janowsky, D.S.; Segal, Neurology and Psychiatry, 81:363-369, Psychiatric Association, 141st Annual
D.S.; Parker, D.C.; and Huey, L.Y. 1959. Meeting, Montreal, Canada, 1988.
Behavioral effects of methadone on McClellan, A.T.; Woody, G.E.; and p. 55.
schizophrenic patients. American O'Brien, C.P. Development of Richard, M.L.; Iiskow, B.I.; and
Journal of Psychiatry, 138:243-245, psychiatric illness in drug abusers: Perry, P.J. Recent psychostimulant
1981. Possible role of drug preference. New use in hospitalized schizophrenics.
Kahn, J.P.; Puertollano, M.A.; England Journal of Medicine, Journal of Clinical Psychiatry,
Schane, M.D.; and Klein, D.F. Ad- 301:1310-1314, 1979. 135:79-83, 1985.
junctive alprazolam for schizophren- McNair, D.M.; Lorr, M.; and Drop- Ritz, M.C.; Lamb, R.J.; Goldberg,
ics with panic anxiety: Clinical pelman, L.F. Profile of Mood States S.R.; and Kuhar, M.J. Cocaine recep-
observations and pathogenic im- Manual. San Diego, CA: EDITS, tors on dopamine transporters are
plications. American Journal of 1971. related to self-administration of co-
Psychiatry, 145:742-744, 1988. caine. Science, 237:1219-1223, 1987.
Miller, E, and Tanenbaum, J.H.
Kesselman, M.S.; Solomon, J.; Drug abuse in schizophrenia. Schneier, F.R., and Siris, S.G. A
Beaudett, M.; and Thornton, B. Hospital & Community Psychiatry, review of psychoactive substance
Alcoholism and schizophrenia. In: 40:847-849, 1989. use and abuse in schizophrenia: Pat-
Solomon, J., ed. Alcoholism and Millman, R.B., and Sbriglio, R. Pat- terns of drug choice. Journal of
Clinical Psychiatry. New York: Nervous and Mental Disease,
terns of use and psychopathology in
Plenum Press, 1982. pp. 69-80. 175:641-642, 1987.
chronic marijuana users. Psychiatric
Khantzian, E.J. The self-medication Clinics of North America, 9:533-545, Siris, S.G.; Kane, J.M.; Frechen, K.;
hypothesis of addictive disorders: 1986. Sellew, A.P.; Mandeli, J.; and
Focus on heroin and cocaine Negrete, J.C.; Knapp, W.P.; Douglas, Fasano-Dube, B. Histories of sub-
dependence. American Journal of D.E.; and Smith, W.B. Cannabis af- stance abuse in patients with post-
Psychiatry, 142:1259-1264, 1985. fects the severity of schizophrenic psychotic depressions. Comprehensive
Knudsen, P., and Vilmar, T. Can- symptoms: Results of a clinical Psychiatry, 29:550-557, 1988.
nabis and neuroleptic agents in survey. Psychological Medicine, Snyder, S.H. The dopamine
schizophrenia. Acta Psychiatrica Scan- 16:515-520, 1986. hypothesis of schizophrenia: Focus
dinavica, 69:162-174, 1984. Pennes, H.H. Clinical reactions of on the dopamine receptor. American
Kolb, L. Drug Addiction: A Medical schizophrenics to sodium amytal, Journal of Psychiatry, 133:197-202,
Problem. Springfield, IL: Charles C pervitin hydrochloride, mescaline 1976.
Thomas, Publisher, 1962. sulfate, and D-lysergic acid Solomon, P. Receipt of aftercare
Kornetsky, C. Hyporesponsivity of diethylamide (LSD25). Journal of services by problem types: Psychi-
chronic schizophrenic patients to Nervous and Mental Disease, atric, psychiatric/substance abuse
dextroamphetamine. Archives of 119:95-112, 1954. and substance abuse. Psychiatric
General Psychiatry, 33:1425-1428, Prosser, R.A., and Pickens, R. Quarterly, 87:180-188, 1986.
1977. Catecholamines, drug abuse and Treffert, D.A. Marijuana use in
Levy, L.; Cameron, D.E.; and schizophrenia. In: Pickens, R.W., schizophrenia: A dear hazard.
Aitken, R.C.G. Observation of two and Heston, L.L., eds. Psychiatric American Journal of Psychiatry,
psychomimetic drugs of piperidine Factors in Drug Abuse. New York: 135:1213-1215, 1978.
derivation-CU 395 (Sernyl) and Cl Grune and Stratton, 1979. Tsuang, MX; Simpson, J.C.; and
400. American Journal of Psychiatry, pp. 285-300. Kronfol, Z. Subtypes of drug abuse
116:843-844, 1960. Rader, L.E.; Rodell, D.E.; Beck, with psychosis. Archives of General
VOL. 16, NO. 1, 1990 79

Psychiatry, 39:141-147, 1982. Drug abuse in mental illness. Lancet,

Downloaded from http://schizophreniabulletin.oxfordjournals.org/ at Purdue University Libraries ADMN on June 17, 2015
van Kanunen, D.P.; Bunney, WE., 1:997, 1988. The Authors
Jr.; Docherty, J.P.; Marder, S.R.; West, P. Interaction of low-dose am-
Ebert, M.H.; Rosenblatt, J.E.; and Lisa Dixon, M.D., is a Research
phetamine use with schizophrenic
Rayner, J.N. d-Amphetamine in- Fellow at the Maryland Psychiatric
outpatients: Three case reports. Research Center, Baltimore, MD.
duced heterogeneous changes in American Journal of Psychiatry,
psychotic behavior in schizophrenia. Gretchen Haas, Ph.D., is an
131:321-323, 1974. Associate Research Professor of
American Journal of Psychiatry,
139:997-999, 1982. Wolkowitz, O.M.; Breier, A.; Doran, Psychology in Psychiatry, Payne
A.R.; Kelsoe, }.; Lucas, P.; Paul, Whitney Clinic, New York
Weil, A.T. Adverse reactions to mari- Hospital—Cornell Medical Center,
juana. New England Journal of Medi- S.M.; and Pickar, D. Alprazolam
augmentation of the antipsychotic New York, NY. Peter Weiden, M.D.,
cine, 282:997-1000, 1970. is Chief, Inpatient Schizophrenia
effects of fluphenazine in schizo-
Weinberger, D.R. Implications of phrenic patients. Archives of General Service, Hillside Hospital, Glen
normal brain development for the Psychiatry, 45:664-670, 1988. Oaks, NY. John Sweeney, Ph.D., is
pathogenesis of schizophrenia. Assistant Professor of Psychiatry;
Archives of General Psychiatry, Wyatt, R.J.; Karoum, R; Suddath, and Allen Frances, M.D., is Pro-
44:660-669, 1987. R.; and Fawcett, R. Persistently fessor of Psychiatry, Department of
Weller, M.P.; Ang, P.C.; Latimer- decreased brain dopamine levels Psychiatry, Payne Whitney Clinic,
Sayer, D.T.; Weller, MR; Ang, P C ; and cocaine. Journal of the American New York Hospital-Cornell Medical
Zachary, A.; and Latimer-Sayer, D.T. Medical Association, 259:29%, 1988. Center, New York, NY.