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Cited by 80Schizophrenia research and treatmentCannabis and Cannabinoid ResearchSubstance Abuse Treatment and Outcomes

Association between cannabis use disorder and schizophrenia stronger in young males than in females

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Hjorthøj, Carsten, Compton, Wilson, Starzer, Marie, Nordholm, Dorte, Einstein, Emily, Erlangsen, Annette, Nordentoft, Merete, Volkow, Nora D. +1 more·2023·Psychological Medicine
DOI 10.1017/s0033291723000880PMC PMC10719679
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Abstract

Background: Previous research suggests an increase in schizophrenia population attributable risk fraction (PARF) for cannabis use disorder (CUD). However, sex and age variations in CUD and schizophrenia suggest the importance of examining differences in PARFs in sex and age subgroups. Methods: We conducted a nationwide Danish register-based cohort study including all individuals aged 16–49 at some point during 1972–2021. CUD and schizophrenia status was obtained from the registers. Hazard ratios (HR), incidence risk ratios (IRR), and PARFs were estimated. Joinpoint analyses were applied to sex-specific PARFs. Results: We examined 6 907 859 individuals with 45 327 cases of incident schizophrenia during follow-up across 129 521 260 person-years. The overall adjusted HR (aHR) for CUD on schizophrenia was slightly higher among males (aHR = 2.42, 95% CI 2.33–2.52) than females (aHR = 2.02, 95% CI 1.89–2.17); however, among 16–20-year-olds, the adjusted IRR (aIRR) for males was more than twice that for females (males: aIRR = 3.84, 95% CI 3.43–4.29; females: aIRR = 1.81, 95% CI 1.53–2.15). During 1972–2021, the annual average percentage change in PARFs for CUD in schizophrenia incidence was 4.8 among males (95% CI 4.3–5.3; p < 0.0001) and 3.2 among females (95% CI 2.5–3.8; p < 0.0001). In 2021, among males, PARF was 15%; among females, it was around 4%. Conclusions: Young males might be particularly susceptible to the effects of cannabis on schizophrenia. At a population level, assuming causality, one-fifth of cases of schizophrenia among young males might be prevented by averting CUD. Results highlight the importance of early detection and treatment of CUD and policy decisions regarding cannabis use and access, particularly for 16–25-year-olds.

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  • The increase in schizophrenia incidence associated with THC and CUD was predominantly among young males 20-30 years of age.

    “More recently, a study based on electronic record over 5 decades in the Danish population reported an increase in the incidence of schizophrenia associated with use of THC and CUD, predominantly among young males 20–30 years of age in whom cannabis use accounted for 30% of the cases [51].”

    From Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits (2025) · cites this paper as [51]

    The Discussion reports a stronger CUD–schizophrenia association in young males and says that, assuming causality, the proportion of cases attributable to CUD in males aged 21–30 may be as high as 25–30%. The study used Danish registers spanning 1972–2021, but it did not directly assess THC exposure; it discusses rising THC potency as a possible explanation. The citing sentence also presents the conditional 30% estimate too definitively. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Cannabis use accounted for 30% of schizophrenia cases in young males 20-30 years of age in the Danish population.

    “More recently, a study based on electronic record over 5 decades in the Danish population reported an increase in the incidence of schizophrenia associated with use of THC and CUD, predominantly among young males 20–30 years of age in whom cannabis use accounted for 30% of the cases [51].”

    From Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits (2025) · cites this paper as [51]

    The Discussion (page not supplied) says that, among Danish males aged 21–30, the proportion of schizophrenia cases attributable to cannabis use disorder may be as high as 25–30%, assuming a causal relationship. The citing sentence presents 30% as a definite figure for cannabis use more broadly, rather than a conditional upper estimate for cannabis use disorder; it also describes the age group as 20–30. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • A study based on electronic records over 5 decades in the Danish population reported an increase in the incidence of schizophrenia associated with use of THC and CUD.

    “More recently, a study based on electronic record over 5 decades in the Danish population reported an increase in the incidence of schizophrenia associated with use of THC and CUD, predominantly among young males 20–30 years of age in whom cannabis use accounted for 30% of the cases [51].”

    From Cannabis, cannabinoids and health: a review of evidence on risks and medical benefits (2025) · cites this paper as [51]

    The Methods describe a Danish register study spanning 1972–2021, and the Results report an association between CUD and incident schizophrenia. The Discussion estimates that 25–30% of cases among males aged 21–30 may be attributable to CUD, conditional on a causal interpretation. The study did not measure THC use as a separate exposure, so its findings do not establish the claimed incidence association for THC use. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Hjorthøj, C., Compton, W., Starzer, M., Nordholm, D., Einstein, E., Erlangsen, A., Nordentoft, M., Volkow, N. D., & Han, B.
Affiliations
  • University of Copenhagen (DK)
  • National Institutes of Health (US)
  • Mental Health Services (DK)
  • Australian National University (AU)
Corresponding author
Hjorthøj, Carsten
ORCID
Venue
Psychological Medicine
Publisher
Cambridge University Press (CUP)
Published
2023-05-04
Volume
53
Issue
15
Pages
7322-7328
ISSN
  • 0033-2917 (ISSN-L)
  • 1469-8978
DOI
10.1017/s0033291723000880
PMC
PMC10719679
OpenAlex
W4368362129
Cited by
80
References
5
Citations by year
2026: 11 · 2025: 30 · 2024: 28 · 2023: 11
FWCI
16.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychological Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
Funders
Lundbeckfonden (R287-2018-1485)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
cannabis use disorder, schizophrenia, sex differences, young adults, cannabis and psychosis, schizophrenia incidence, cannabis policy
MeSH terms
Cannabis, Marijuana Abuse, Female, Humans, Male, Schizophrenia, Cohort Studies, Substance-Related Disorders

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