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Peer-reviewedCC BY 4.0European Psychiatry

Real-world effectiveness of psychiatric pharmacotherapies in reducing the risk of substance use- and psychiatric hospitalisations in cannabis use disorder – An exploratory nationwide register-based study

  • Antti Mustonen1,2,3
  • Solja Niemelä4,5
  • Markku Lähteenvuo6
  • Alexander Denissoff4,5
  • Antti Tanskanen2,6
  • Ellenor Mittendorfer-Rutz2
  • Jari Tiihonen2,6,7,8
  • Heidi Taipale2,6,8
8 affiliations
  1. 1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
  2. 2Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
  3. 3Department of Psychiatry, Seinäjoki Central Hospital, Seinäjoki, Finland
  4. 4Department of Psychiatry, Faculty of Medicine, University of Turku, Turku, Finland
  5. 5Addiction Psychiatry Unit, Department of Psychiatry, Turku University Hospital, Wellbeing County of South-West Finland, Turku, Finland
  6. 6Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland
  7. 7Neuroscience Center, University of Helsinki, Helsinki, Finland
  8. 8Center for Psychiatry Research, Stockholm Region, Stockholm, Sweden
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Abstract

Background: Pharmacotherapies have shown limited efficacy in cannabis use disorder (CUD). This exploratory study examined the real-world effectiveness of commonly used psychiatric medications in reducing the risk of substance use and psychiatric hospitalisations among individuals with CUD.

Methods: We conducted a nationwide prospective cohort study using Swedish health and administrative registers. The cohort included 51,947 individuals aged 16–64 years with a first CUD diagnosis (ICD-10 F12) between 2006 and 2021. Medication use was modelled as time-dependent with the PRE2DUP method. Within-individual Cox regression was used to compare hospitalisation risk during medication use versus non-use. The primary outcome was hospitalisation for substance use disorder (SUD).

Results: ADHD (aHR: 0.85; 95% CI: 0.81–0.88) and SUD medications (aHR: 0.97; 0.93–0.99) were associated with reduced SUD hospitalisation risk. In contrast, antipsychotics (aHR: 1.12; 1.09–1.15), antidepressants (aHR: 1.09; 1.06–1.11), and benzodiazepines (aHR: 1.14; 1.11–1.17) were associated with increased risk, while mood stabilisers showed no significant effect. Specific agents, including clozapine (aHR: 0.47; 0.31–0.73), naltrexone (aHR: 0.79; 0.71–0.88), buprenorphine (aHR: 0.92; 0.88–0.96), lisdexamfetamine (aHR: 0.74; 0.69–0.79), methylphenidate (aHR: 0.90; 0.86–0.94), and ADHD polytherapy (aHR: 0.85; 0.75–0.96), were associated with reduced risk.

Conclusions: Most psychiatric medications were not associated with a reduced risk of SUD in individuals diagnosed with CUD. However, pharmacotherapies for ADHD, opioid or alcohol use disorder, and treatment-resistant schizophrenia were linked to better outcomes, likely reflecting the underlying clinical trajectories of other comorbid psychiatric disorders rather than direct therapeutic effects on CUD.

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Cite

BibTeXRIS
BibTeX
@article{mustonen2026realworld,
  title = {{Real-world effectiveness of psychiatric pharmacotherapies in reducing the risk of substance use- and psychiatric hospitalisations in cannabis use disorder – An exploratory nationwide register-based study}},
  author = {Antti Mustonen and Solja Niemelä and Markku Lähteenvuo and Alexander Denissoff and Antti Tanskanen and Ellenor Mittendorfer-Rutz and Jari Tiihonen and Heidi Taipale},
  journal = {European Psychiatry},
  year = {2026},
  month = aug,
  doi = {10.1192/j.eurpsy.2026.12250},
  url = {https://doi.org/10.1192/j.eurpsy.2026.12250},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Real-world effectiveness of psychiatric pharmacotherapies in reducing the risk of substance use- and psychiatric hospitalisations in cannabis use disorder – An exploratory nationwide register-based study
AU  - Antti Mustonen
AU  - Solja Niemelä
AU  - Markku Lähteenvuo
AU  - Alexander Denissoff
AU  - Antti Tanskanen
AU  - Ellenor Mittendorfer-Rutz
AU  - Jari Tiihonen
AU  - Heidi Taipale
PY  - 2026
DA  - 2026/08/12
JO  - European Psychiatry
DO  - 10.1192/j.eurpsy.2026.12250
UR  - https://doi.org/10.1192/j.eurpsy.2026.12250
AB  - Background: Pharmacotherapies have shown limited efficacy in cannabis use disorder (CUD). This exploratory study examined the real-world effectiveness of commonly used psychiatric medications in reducing the risk of substance use and psychiatric hospitalisations among individuals with CUD.  Methods: We conducted a nationwide prospective cohort study using Swedish health and administrative registers. The cohort included 51,947 individuals aged 16–64 years with a first CUD diagnosis (ICD-10 F12) between 2006 and 2021. Medication use was modelled as time-dependent with the PRE2DUP method. Within-individual Cox regression was used to compare hospitalisation risk during medication use versus non-use. The primary outcome was hospitalisation for substance use disorder (SUD).  Results: ADHD (aHR: 0.85; 95% CI: 0.81–0.88) and SUD medications (aHR: 0.97; 0.93–0.99) were associated with reduced SUD hospitalisation risk. In contrast, antipsychotics (aHR: 1.12; 1.09–1.15), antidepressants (aHR: 1.09; 1.06–1.11), and benzodiazepines (aHR: 1.14; 1.11–1.17) were associated with increased risk, while mood stabilisers showed no significant effect. Specific agents, including clozapine (aHR: 0.47; 0.31–0.73), naltrexone (aHR: 0.79; 0.71–0.88), buprenorphine (aHR: 0.92; 0.88–0.96), lisdexamfetamine (aHR: 0.74; 0.69–0.79), methylphenidate (aHR: 0.90; 0.86–0.94), and ADHD polytherapy (aHR: 0.85; 0.75–0.96), were associated with reduced risk.  Conclusions: Most psychiatric medications were not associated with a reduced risk of SUD in individuals diagnosed with CUD. However, pharmacotherapies for ADHD, opioid or alcohol use disorder, and treatment-resistant schizophrenia were linked to better outcomes, likely reflecting the underlying clinical trajectories of other comorbid psychiatric disorders rather than direct therapeutic effects on CUD.
SN  - 0924-9338
SN  - 1778-3585
ER  -