Running head: SUBSTANCE ABUSE AND SCHIZOPHRENIA

Relationship between Substance Abuse and the Development of Schizophrenia

Miranda Paige
Salt Lake Community College

SUBSTANCE ABUSE AND SCHIZOPHRENIA

Abstract
Review of literature to discuss the implications of the relationship between history of substance
abuse and the manifestation of schizophrenia. Discusses the different substances that are
discussed, measures of procedures, neurological aspects, psychosocial functioning and cognitive
functioning. Proposed that a predisposition for psychosis is influenced to occur along with
substance abuse, especially during the adolescent years. The drugs alter the brain structure and
destroy important brain synapses which results in psychosis. Patients also have a high
comorbidity to abuse substances due to addiction and to reverse the negative effects of
antipsychotics. The review covers many articles that demonstrate the correlation of drug use and
schizophrenia, along with the genetic implications of the illness.
Keywords: schizophrenia, substance abuse, drugs, genetics, psychosis, neurobiology

SUBSTANCE ABUSE AND SCHIZOPHRENIA

Relationship between Substance Abuse and the Development of Schizophrenia

Schizophrenia is a diverse psychiatric disorder, whereas the causes of the disorder are
still not clear to researchers. Schizophrenia is believed to be the product of a mixture of genetics
and environmental factors. In past research, it was thought to be predominantly genetic
heritability that 10% of the first degree relatives have the risk of getting it, and 80% of that
population has an increased risk (Huabing et al., 2014). However, drug use has been found to be
an environmental factor that has demonstrated a large influence on the development of
schizophrenia. There is still some controversy of whether or not certain substances contribute to
drug-induced psychosis, but the general consensus is that the use of illicit substances before the
first break of psychosis is a precipitant for the disorder (as cited in Hansen, Nausheen, Hart, &
Kingdon, 2013).
This review of literature considers the implications of substance abuse contributing to the
cause of schizophrenia by comparing various substances and history of abuse, research design,
neurobiological aspects, and cognitive and psychosocial functioning.
Drug Abuse and History of Abuse in Research Subject Participants
Certain substances, such as methamphetamine, cannabis, and cocaine, were used as
research criteria for various studies to demonstrate that history of substance abuse and a genetic
predisposition contributes to the onset of psychosis. Each research study had different methods
of measuring the amount and the length of drug use, but they all had similar findings in their
research. Huabing et al. (2014) had studied subjects who met the DSM-IV criteria for lifetime
methamphetamine dependence. Cannabis dependence was tested on both former and current
users (Fernandez-Espejo, Viveros, Nez, Ellenbroek, & Rodriguez de Fonseca, 2009) who also
had a genetic vulnerability towards the illness. Cocaine was administered to rats by Karlsson,
Kircher, Shaham, & O'Donnell, developed a dependence and relapse roughly compared to
human addiction (2013). Other studies by Fukunaga & Kysaker (2013) suggested alcoholism as a
factor and as well as other unspecified substances.
Implemented Research Procedure Designs
The procedure by Huabing et al. analyses 15 methamphetamine users with schizophrenic
parents, and analyzes 15 siblings of the methamphetamine users as a control group, that are nonusers of the drug. The results of the experiment after a 5 year follow up showed that 7 of the 15
meth users were diagnosed with schizophrenia, while 1 of the 15 sibling control group was
diagnosed (2014). This demonstrated point of it was see that meth affects the development of
schizophrenia, and the interaction of meth and genetics that play a role in the causes of the
disorder.
Fukunaga & Kysaker described their procedures with diagnosed schizophrenic
incarcerated criminals by reviews, diagnoses, interviews, subtests, analyses, and looking at their
legal records of substance abuse and violence. All of the subjects consented and had no
interventions performed prior to the testing. The researchers analyzed all the information and
found that the larger numbers of convictions, larger history of substance abuse, and more

SUBSTANCE ABUSE AND SCHIZOPHRENIA

positive symptoms show more distinguishably in people with schizophrenia who have a criminal
record consisting of drug use and violence (2013).
Many of these studies were based on human subjects with addiction, but animal models
were also used. Karlsson et al. (2013) designed their research based on rat models with a
neonatal ventral hippocampal lesion (NVHL), which resembles a schizophrenic brain of humans,
with the purpose to make the rats react to cocaine as an addiction, cravings, extinction and
reinstatement of the addiction. The NVHL rats increased their resistance to extinction of the
habit, and showed higher cue-induced reinstatement of cocaine compared to the control group.
The purpose of this study was to demonstrate comorbidity of substance addiction and
schizophrenia.
Many of these designs were very different, and it would very hard to replicate with the
same results. Some of the procedures were objective and needed different control groups and
other variables to study. The interview tests werent very reliable because its subjects were
giving testimonials and could easily lie. Other animal models would be needed to point to
narrower conclusions and give more insight for human studies. Many articles did not describe
the exact measures and means of going about the tests, and it did not specify each vital variable.
Neurobiological Aspects
It is a known fact that long histories of drug abuse alter the brains structure, and it is also
know that patients with schizophrenia have abnormal brain structures compared to a normal
brain.
During adolescence, the brain goes through some of its peak processing and changes in
neurotransmitters. The normal development of an adolescent brain will reorganize its processes
through a system called pruning by getting rid of unnecessary synapses and strengthen the
ones that get used often. It is suggested that schizophrenia might arise from abnormal amounts of
pruning after over 35% of synapses are lost (Nimwegen et al., 2005). The reward system of the
brain is affected by stimulants as it anticipates and craves the drug to be able to feel pleasure by
releasing dopamine. In the same study, it was hypothesized that abnormalities in the
hippocampus and prefrontal cortex created the positive reinforcing behavior of drug reward and
reduce inhibitory control. Nimwegen et al. continued to say that drugs, such as cannabis and
various amphetamines, prominently affected the brains dopamine levels, and the prolonged use
of the drugs may start the onset of the first psychotic episode.
In another study it was confirmed that cannabis users that experienced their first
schizophrenic episode showed extraneous reduction of brain volume after a five year follow-up.
The cannabinoid receptors with altercations were caused by the genetic predisposition towards
schizophrenia, and activation of those receptors could contribute to the development of the
illness. It was contradicted by other studies found that some genetic altercations of the gene that
contributes to the heritability of the disorder can act as a protectant rather than a vulnerability.
(Fernandez-Espejo et al, 2009). To add to that, it was suggested that lifetime use of cannabis in

SUBSTANCE ABUSE AND SCHIZOPHRENIA

patients with schizophrenia had better cognitive functioning than patients who did not use
cannabis (Rabin, Gidden, & George, 2014).
In the study of the self-administering cocaine rats, the NVHL rats showed significant cell
loss and ventricle enlargement compared to the sham-operated control rats. This meant that the
pleasure seeking systems of the brains were altered, which explained the question of why
patients with schizophrenia tend to abuse substances. This model could have the purpose of
determining the factors of the brain that affect the comorbidity of schizophrenia and addiction,
and possibly shed light for approaches in therapy to treat this diagnosis.
Many of these tests were designed differently and measured results that were different.
Some of the experiments were objective just to show one aspect rather than the whole picture.
The results for cannabis users varied, and were objective with the means of the matter. More
research needs to be conducted on how cannabinoids could protect against the development of
schizophrenia and use different ways of gathering conclusions. As a whole, the majority of the
articles pointed towards the same basis that substance abuse, especially during adolescence,
alters the brain structure and neurotransmitters which more easily brings out the onset of
schizophrenia.
Cognitive and Psychosocial Functioning
There are many various positive and negative symptoms in schizophrenic patients who
abuse drugs. The effects of anhedonia and dysphoria are fairly common in those who are
predisposed to the condition, and tend to lower cognitive functioning (Nimwegen et al., 2005).
This also tends to increase the behaviors associated with pleasure seeking, recklessness, and
violence as claimed by Fukunaga & Kysaker. Disordered cognition is associated with not
knowing social norms, inappropriate behaviors, not being able to differentiate between rights and
wrongs, and violence when assessed in criminal records. Patients without these cognitive
abilities tend to experience more legal issues and not being able to find solutions to those issues.
(2013)
Cognitive tests on methamphetamine users resulted in more errors with visual tests, had
longer reaction time, and longer image recall. The deficits in cognition were observed more often
in the abusers of the substance than in the siblings of those abusers. Other studies added to this
and showed that substance abuse in schizophrenic patients had larger impairments in tests and
recall tests after a follow-up, which demonstrated the key elements of the procedures.
Conclusion
Substance abuse is a large risk factor for those who are already predisposed to schizophrenia, as
it can affect neurological development by producing abnormalities in the brain, especially during
adolescence. It lowers cognitive abilities and alters neurological structures. Not only does drug
use contribute solely to the etiology of psychosis, but many of those patients continue to abuse
drugs which creates more abnormalities in the brain structure, which can heighten the amount of
positive and disorganized symptoms and lengthen the course of the illness.

SUBSTANCE ABUSE AND SCHIZOPHRENIA

The direction of future research should aim towards finding a treatment for the addictions of
people with psychosis. This would help those who are currently struggling with addiction, and
advert against those who are starting the road towards substance abuse. Nimwegen et al. suggests
that the next step towards treatment is focusing attention on patients that experience dysphoria
and anhedonia. Its suggested that the antipsychotics cause these feelings and the patient feels a
need to feel something so they turn to substances. Its important to take an account of the
experiences general well-being of the patient. They go on to suggest more research on the effects
antipsychotics is necessary to improve the design of the prescriptions and the patients quality of
life (2005).

SUBSTANCE ABUSE AND SCHIZOPHRENIA

References
Fernandez-Espejo, E.,Viveros, M., Nez, L., Ellenbroek, B., & Rodriguez de Fonseca, F.
(2009). Role of cannabis and endocannabinoids in the genesis of schizophrenia.
Psychopharmacology, 206(4), 531-549. doi:10.1007/s00213-009-1612-6
Fukunaga, R., & Kysaker, P. (2013). Criminal history in schizophrenia: Associations with
substance use and disorganized symptoms. Journal of Forensic Psychiatry & psychology,
24(3), 293-308. doi:10.1080/14789949.2013.776617
Hansen, L., Nausheen, B., Hart, D., & Kingdon, D. (2013). Movement disorders in patients with
schizophrenia and a history of substance abuse. Human Psychopharmacology: Clinical &
Experimental, 28(2), 192-197. doi:10.1002/hup.2305
Huabing, L., Qiong, L., Enhua, X., Qiuyun, L., Zhong, H., & Xilong, M. (2014).
Methamphetamine enhances the development of schizophrenia in first-degree relatives of
patients with schizophrenia. Canadian Journal of Psychiatry, 59(2), 107-113.
Karlsson, R., Kircher, D., Shaham, Y., & O'Donnell, P. (2013). Exaggerated cue-induced
reinstatement of cocaine seeking but not incubation of cocaine craving in a developmental rat
model of schizophrenia. Psychopharmacology, 226(1), 45-51. doi:10.1007/s00213-0122882-y
Nimwegen, L.V., Haan, L.D., Beveren, N.V., Brink, W.V.D, & Linszen, D.(2005). Adolescence,
schizophrenia and drug abuse: A window of vulnerability. Acta Psychiatrica Scandinavica,
111(427), 35-42. doi:10.1111/j.1600-0447.2005.00543.x
Rabin, R., Giddens, J., & George, T. (2014). Relationship between tobacco and cannabis use
status in outpatients with schizophrenia. American Journal on Addictions, 23(2), 170-175.
doi:10.1111/j.1521-0391.2013.12084.x