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Is There a Link Between Cannabis Use Disorder and Schizophrenia in Young Males?

  • Authors: News Author: Megan Brooks; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 6/9/2023
  • Valid for credit through: 6/9/2024, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for primary care clinicians, pediatricians, psychiatrists, addiction medicine specialists, nurses, physician assistants, nurse practitioners, pharmacists, and other clinicians who treat and manage patients who might use cannabis.

The goal of this activity is for members of the healthcare team to be better able to evaluate trends in the risk for schizophrenia associated with cannabis use disorder.

Upon completion of this activity, participants will:

  • Assess previous estimates regarding the risk for psychotic disorders and cannabis use
  • Evaluate trends in the risk for schizophrenia associated with cannabis use disorder
  • Outline implications for the healthcare team


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News Author

  • Megan Brooks

    Freelance writer, Medscape


    Megan Brooks has no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine


    Charles P. Vega, MD, has the following relevant financial relationships:
    Consultant or advisor for: Boehringer Ingelheim; GlaxoSmithKline; Johnson & Johnson

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  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC 


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  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC


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Is There a Link Between Cannabis Use Disorder and Schizophrenia in Young Males?

Authors: News Author: Megan Brooks; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 6/9/2023

Valid for credit through: 6/9/2024, 11:59 PM EST


Clinical Context

There are many controversies regarding the health effects of cannabis, and one of them centers on the relationship between cannabis use and the risk for schizophrenia. Some, but not all, research has demonstrated a significant link between cannabis use and a higher prevalence of psychosis. Marconi and colleagues performed a review and meta-analysis of this relationship, and their results were published in the September 2016 issue of Schizophrenia Bulletin.[1]

Eighteen studies were included in the systematic review, and 10 provided outcomes that could be measured in the meta-analysis. A total of 66,816 individuals were included in these studies. Compared with a cohort with no cannabis use, those with the heaviest cannabis use experienced an odds ratio (OR) of 3.90 (95% CI, 2.84-5.34) for schizophrenia and other psychotic disorders. The median OR for schizophrenia or psychosis with any cannabis use was 1.97 (95% CI, 1.68-2.31).

The authors of the current study note that the potential effect of cannabis in promoting incident schizophrenia appears to be stronger in males. In addition, the increasing concentration of delta-9-tetrahydrocannibinol in cannabis may also be having an effect in promoting more psychotic disorders. The authors of the current study examine specifically how sex and time have affected any relationship between cannabis use disorder (CUD) and schizophrenia.

Study Synopsis and Perspective

A new study confirms the robust link between cannabis use and schizophrenia among men and women, but suggests that young men may be especially susceptible to schizophrenia from cannabis abuse.

Of note, the investigators estimate that roughly 15% of schizophrenia cases among young males may be preventable by avoiding CUD

“The entanglement of substance use disorders and mental illnesses is a major public health issue, requiring urgent action and support for people who need it,” study coauthor Nora Volkow, MD, director of the National Institute on Drug Abuse, says in a news release.

“As access to potent cannabis products continues to expand, it is crucial that we also expand prevention, screening, and treatment for people who may experience mental illnesses associated with cannabis use,” Dr Volkow adds.

The study was published online May 4 in Psychological Medicine.[2]

A Modifiable Risk Factor

The researchers analyzed Danish registry data spanning 5 decades and representing more than 6.9 million people in Denmark to estimate the population-level percentage of schizophrenia cases attributable to CUD.

A total of 60,563 participants were diagnosed with CUD. Three quarters of cases were in men; there were 45,327 incident cases of schizophrenia during the study period.

The overall adjusted hazard ratio (aHR) for CUD on schizophrenia was slightly higher among males than females (aHR, 2.42 vs 2.02); however, among those aged 16 to 20 years, the adjusted incidence risk ratio (aIRR) for males was more than twice that for females (aIRR, 3.84 vs 1.81).

The researchers estimate that in 2021, about 15% of schizophrenia cases among males aged 16 to 49 years could have been avoided by preventing CUD compared with 4% among females in this age range.

For young men aged 21 to 30 years, the proportion of preventable schizophrenia cases related to CUD may be as high as 30%, the authors report.

“Alongside the increasing evidence that CUD is a modifiable risk factor for schizophrenia, our findings underscore the importance of evidence-based strategies to regulate cannabis use and to effectively prevent, screen for, and treat CUD as well as schizophrenia,” the researchers write.

Legalization Sends the Wrong Message

In a press statement, lead investigator Carsten Hjorthøj, PhD, from the University of Copenhagen, Denmark, notes that “increases in the legalization of cannabis over the past few decades have made it one of the most frequently used psychoactive substances in the world, while also decreasing the public’s perception of its harm. This study adds to our growing understanding that cannabis use is not harmless, and that risks are not fixed at one point in time.”

In a prior study, Dr Hjorthøj and colleagues found that the proportion of new schizophrenia cases attributable to CUD has consistently increased over the past 20 years, as reported by Medscape Medical News.[3]

“In my view, the association is most likely causative, at least to a large extent,” Dr Hjorthøj told Medscape Medical News at the time this research was published.

“It is of course nearly impossible to use epidemiological studies to actually prove causation, but all the numbers behave exactly in the way that would be expected under the theory of causation,” Dr Hjorthøj added.

The study received no specific funding. The authors have disclosed no relevant financial relationships.

Psychol Med. Published online May 4, 2023.

Study Highlights

  • Investigators examined Danish national health registries among adults between ages 16 and 49 years from 1972 to 2021.
  • The study focused on the relationship between diagnosis codes for schizophrenia and CUD. CUD is usually defined as continued cannabis use despite significant negative consequences associated with cannabis.
  • Researchers also examined records for concomitant alcohol use disorder and other psychiatric disorders, but they could not identify cigarette smoking from the registry records.
  • The main study outcome was the population attributable risk fraction (PARF) estimated for cannabis in possibly promoting schizophrenia. Researchers examined the PARF over time and by sex.
  • The study analysis was adjusted to account for other substance use, other psychiatric illness, and any family history of psychiatric illness.
  • There were 45,327 cases of schizophrenia among 6,907,859 adults and 129,521,260 life-years at risk.
  • The unadjusted HR for schizophrenia associated with CUD was 30.18, but the adjusted HR was 2.31 (95% CI, 2.24-2.40). The HR for males (2.42) was higher than that for females (2.02).
  • There was a clear gradual increase in HR associating CUD and schizophrenia among men between 1972 and 2021, with the HR in the final years of the study around 3. There was no such pattern among women.
  • Similarly, the PARFs for schizophrenia related to CUD increased more rapidly among men vs women. Assuming causality, CUD accounted for 15% of cases of schizophrenia among men in 2021. The PARF among women in 2021 for CUD was just 4%.
  • The adjusted incidence rate ratio (IRR) for CUD related to schizophrenia among 16- to 20-year-old males was 3.84 (95% CI, 3.43-4.29), whereas the respective value among females in the same age group was 1.81 (95% CI, 1.53-2.15). The IRR for CUD related to schizophrenia fell to 2.58 (95% CI, 2.38-2.79) among males between the ages of 21 and 25 years, but remained among females in this age group.
  • There was a trend over time of increasing PARFs for CUD and schizophrenia among males between 20 and 30 years of age, but the same trend was not found among younger males or females.

Implications for the healthcare team

  • A previous meta-analysis found that any cannabis use was associated with a higher risk for psychotic disorders, with the heaviest use of cannabis associated an approximate 4-fold increase.
  • The current study finds a significant association between CUD and the risk for schizophrenia, with a stronger association among males vs females. Assuming causality, CUD accounted for 15% of cases of schizophrenia among men in 2021, and the risk for schizophrenia related to CUD was highest among males between the ages of 16 and 20 years. The relationship between CUD and schizophrenia increased over time among males.
  • The healthcare team should counsel adolescents to avoid cannabis and be aware of the importance of early detection and management due to the significant associations between CUD and the risk for schizophrenia among young males.


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