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Original Investigation
July 21, 2021

Development Over Time of the Population-Attributable Risk Fraction for Cannabis Use Disorder in Schizophrenia in Denmark

Author Affiliations
  • 1Copenhagen Research Center for Mental Health–CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
  • 2Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
  • 3The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPsych, Copenhagen and Aarhus, Denmark
JAMA Psychiatry. 2021;78(9):1013-1019. doi:10.1001/jamapsychiatry.2021.1471
Key Points

Question  Has the population-attributable risk fraction for cannabis use disorder in schizophrenia increased over time, as would be expected with increasing use and potency of cannabis?

Findings  In this Danish nationwide, register-based cohort study, the population-attributable risk fraction for cannabis use disorder in schizophrenia increased from approximately 2% in the period to 1995 to approximately 6% to 8% since 2010.

Meaning  These findings may indicate that cannabis use disorders are associated with an increase in the proportion of cases of schizophrenia.


Importance  Cannabis use and potency of cannabis have increased during the past 2 decades. If the association between cannabis use and schizophrenia is causal, this should be reflected in an increase in the proportion of cases of schizophrenia being attributable to cannabis, the population-attributable risk fraction (PARF).

Objective  To determine whether the PARF for cannabis use disorder in schizophrenia has increased over time.

Design, Setting, and Participants  This nationwide, register-based historical prospective cohort study included all people in Denmark born before December 31, 2000, who were alive and 16 years or older at some point from January 1, 1972, to December 31, 2016. Data analysis was performed from August 2020 to April 2021.

Exposure  Diagnosis of cannabis use disorder.

Main Outcomes and Measures  Diagnosis of schizophrenia, with estimated PARF of cannabis use disorder in schizophrenia from 1972 to 2016.

Results  A total of 7 186 834 individuals were included in the analysis, including 3 595 910 women (50.0%) and 3 590 924 men (50.0%). The adjusted hazard ratio for schizophrenia fluctuated at approximately 4 (with 95% CIs ranging from approximately 3 to 6) throughout most of the study period when people diagnosed with cannabis use disorder were compared with those without cannabis use disorder. The PARF of cannabis use disorder in schizophrenia also fluctuated, but with clear evidence of an increase from 1995 (when the PARF was relatively stable around 2.0%, with a 95% CI of approximately 0.3% to either side) until reaching some stability around 6.0% to 8.0% (with a 95% CI of approximately 0.5% to either side) since 2010.

Conclusions and Relevance  The results from these longitudinal analyses show the proportion of cases of schizophrenia associated with cannabis use disorder has increased 3- to 4-fold during the past 2 decades, which is expected given previously described increases in the use and potency of cannabis. This finding has important ramifications regarding legalization and control of use of cannabis.

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    1 Comment for this article
    Pushing it
    Jeoffry Gordon, MD, MPH | Retired
    As the authors of this study explicitly say, "The PARF is an estimate of the proportion of cases of schizophrenia that would have been prevented if no individuals had been exposed (in this case to cannabis use disorder), under the assumption that the association between cannabis and schizophrenia may be causal. In light of this assumption, the PARF cannot confirm whether an association is truly causal. However, an increase in the PARF co-occurring alongside an increase in either the proportion using cannabis or in the potency of cannabis would be expected if the association was indeed causal."

    Nonetheless, the
    authors pullout all strings and every tool to stretch the possibility of a causal relationship between cannabis use and schizophrenia. During the period of the study, evidently cannabis (and more potent cannabis) generally became more available in Denmark. It is relevant but not included to have data comparing the increased use of cannabis in the general Denmark population with that among schizophrenic persons. As the incidence of new onset schizophrenia is in the teenage and young adult years where cannabis use is more common, not discussed was the possibility of schizophrenics self medicating with cannabis to relieve symptoms as it became more available.