What's The Link Between Schizophrenia and Substance Abuse Disorder?

Schizophrenia is a chronic mental health condition that affects the way a person thinks. The symptoms often begin in adolescence and then peak in the 30s-50s. It's a disease that can cause individuals to have disorganized thoughts and behavior, experience delusions (firm beliefs that are demonstrably false), and hallucinations (perceive something that isn't there).

As of 2019, schizophrenia affects an estimated 14.2-23.6 million people worldwide. It is a serious illness which causes significant impairments to those affected by it, and is associated with a much lower life expectancy compared to the average population. People with schizophrenia experience higher rates of heart disease, substance abuse and suicide. They often don't get the care they need, and are more vulnerable to homelessness and poverty.

People with schizophrenia are much more likely to have a substance abuse disorder, (47% compared to 16% in non-schizophrenics). And those with both conditions often experience more severe symptoms, have trouble adhering to their medication, increased hospital stays, and more suicide attempts. So a comorbid substance abuse disorder alongside schizophrenia is associated with a worse course for the illness overall.

Why is this? Why are people with schizophrenia more likely to have substance abuse disorders? And does substance abuse trigger schizophrenia in any way?

There are several explanations—and they may overlap with each other. They aren't necessarily the whole story. But they can help us understand the disease better, and possibly provide a framework for developing medications that can aid in treating both conditions.

Starting off, there is a link between substance abuse disorder and the later development of schizophrenia, as many individuals use substances prior to the development of the disease. But is it as simple as to say that substance abuse causes the disease?

Well, schizophrenia can't be narrowed down to a single cause. It's a complex mixture of multiple genes, early and late environmental factors, and differences in several important brain pathways.

A number of theories have been proposed to explain this association. Some of which suggest that substance abuse is one of the environmental risks that increases the likelihood of schizophrenia in already likely individuals. (Those with genetic or environmental predispositions to developing the disease).

Others suggest that substance abuse is a way for affected individuals to self-medicate for the symptoms of their illness, or for the side-effects of their antipsychotic medication. Though the evidence for this theory is conflicting. As abstaining from the substance often improves symptoms in affected individuals.

Another theory, known as the "Primary Addiction Hypothesis", suggests that both schizophrenia and substance use disorders share a common origin in overlapping neural circuits, and that substance use may be related to a dysfunction of the brain reward circuit that occurs in schizophrenics.

The increase in substance abuse in the prodromal state (the early symptoms of a disease before full onset) might be because they want to reduce the cognitive deficits and negative symptoms seen in this stage, or it could be because their unique brain pathways or genetics predispose them to substance abuse.

Interestingly, the non-psychotic siblings of schizophrenic individuals also have higher rates of substance abuse. This might be because they genetically share similar reward-circuitry. But it could also be self-medication for symptoms that don't meet the threshold for schizophrenia, but are nevertheless still there.

What are the most common substances in use for this population? And how does the type of substance affect the development of schizophrenia?

The most prevalent is tobacco, followed by cannabis, alcohol, and cocaine.

With regards to specific substances, there is a well-established link between cannabis use in adolescence and the development of psychotic symptoms. Cannabis use in adolescents is associated with a higher risk of developing psychotic symptoms. It is also linked to the earlier onset of psychotic symptoms in people with schizophrenia.

Not all individuals who develop schizophrenia use cannabis, but cannabis use in adolescence is a risk factor, when the brain isn't fully developed. A large study from Denmark concluded that proportion of cases of schizophrenia associated with cannabis use disorder has increased 3- to 4-fold during the past 2 decades, which correlates with the increase in potency and availability of cannabinoids.

Other environmental and biological factors (such as childhood trauma) also influence the risk of developing schizophrenia.

Although it's causative role in schizophrenia us unclear, tobacco smoking has severe health consequences that negatively affect the user's lifespan. It can also interfere with the effectiveness of antipsychotic medication, and thus is highly discouraged. Alcohol can, in cases of chronic, heavy use, cause alcohol induced psychosis. This psychosis can look like schizophrenia but has an older average age of onset and often involves other alcohol-related cognitive deficits. Stimulants (like cocaine and methamphetamines) can also exacerbate psychotic symptoms in people with schizophrenia, and may precipitate psychosis in those with no prior disposition.

That being said, schizophrenia is highly heritable. With a 40-50% concurrence of the disease seen in twins with the same DNA. There are genes that are linked to the development both schizophrenia and substance use. It is possible that these genes increase both the probability of substance abuse and that of developing schizophrenia. On the other hand, individuals with these genes might be more likely to get schizophrenia only after they use substances, in which case the substance use and the genes work as a dual risk factor.

Regardless, while substance use alone is not enough to cause schizophrenia without the complex underlying backbone of genetics and neural pathways, some substances are risk factors dependent upon age, and prior disposition.

In order to assist the substantial population that is already affected by the disease, there should be careful screening for comorbid substance use disorders, social support, and an integrated approach to treating both conditions. These are vital to improve the clinical outcome of schizophrenia for people worldwide.

So, to summarize:

1. People with schizophrenia are at higher risk for substance use disorder.

2. Substance abuse disorder is associated more severe symptoms, lower lifespans, and worse outcomes for individuals with schizophrenia.

3. Schizophrenia is caused by a complex mixture of genetics, neurotransmitters and environmental stressors, all of which play a partial role in the development of the disease.

4. Schizophrenia and substance use disorders may share a commonality in brain pathways that results in individuals being predisposed to both conditions.

5. Substance abuse alone is not sufficient to cause schizophrenia, but certain substances can increase the risk or trigger an earlier age of onset in predisposed individuals.

6. Cannabis use in adolescence is a significant risk factor for the later development of schizophrenia, and may serve as the trigger for psychosis in predisposed individuals.

7. Other substances like stimulants have the potential to induce psychosis, but not necessarily schizophrenia.

References:

1. Manseau M, Bogenschutz M. Substance Use Disorders and Schizophrenia. FOCUS. 2016 Jul;14(3):333–42.

2. Ward HB, Nemeroff CB, Carpenter L, Grzenda A, McDonald WM, Rodriguez CI, et al. Substance use disorders in schizophrenia: Prevalence, etiology, biomarkers, and treatment. Personalized Medicine in Psychiatry [Internet]. 2023 Jul 1;39-40(100106):100106. Available from: https://www.sciencedirect.com/science/article/abs/pii/S2468171723000078

3. Khokhar JY, Dwiel LL, Henricks AM, Doucette WT, Green AI. The Link between Schizophrenia and Substance Use disorder: a Unifying Hypothesis. Schizophrenia Research [Internet]. 2019;194(1):78–85. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094954/

4. Hjorthøj C, Posselt CM, Nordentoft M. Development Over Time of the Population-Attributable Risk Fraction for Cannabis Use Disorder in Schizophrenia in Denmark. JAMA Psychiatry [Internet]. 2021 Sep 1;78(9):1013–9. Available from: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2782160?guestAccessKey=6d4e6058-7b5f-4e7a-997e-12d59f4a9522&utm_source=pocket_mylist

5. Tumenta T, Oluwatoyin Oladeji, Gill M, Khan BA, Olayinka O, Chiedozie Ojimba, et al. Substance Use Patterns and Schizophrenia Spectrum Disorders: A Retrospective Study of Inpatients at a Community Teaching Hospital. Journal of Clinical Medicine Research [Internet]. 2020 [cited 2026 Jan 16];12(12):803–8. Available from: https://www.jocmr.org/index.php/JOCMR/article/view/4380/25893303

6. Ding JB, Hu K. Cigarette Smoking and Schizophrenia: Etiology, Clinical, Pharmacological, and Treatment Implications. Faden J, editor. Schizophrenia Research and Treatment [Internet]. 2021 Dec 13;2021:1–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687814/

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