Cannabis Use Disorder May Reduce Risk of Digestive Disorders in Schizophrenia

Cannabis use disorder (CUD) was associated with decreased risk of digestive disorders and inflammatory bowel disease (IBD) in people with schizophrenia, but not in sex- and age-matched controls without schizophrenia, according to a study published in Psychological Medicine.¹ Cannabis has been used to alleviate gastrointestinal symptoms including abdominal pain, nausea, and diarrhea in the general population. In patients with schizophrenia, cannabis may be linked to elevated risk of all-cause mortality but decreased risk of mortality from digestive organ diseases, according to a large prospective register-based study.² 

Julie Aamand Olesen, of the Copenhagen Research Center for Mental Health – CORE, University Hospital, Denmark, and colleagues examined data from the Psychiatric Central Research Registry of Denmark to identify 21066 individuals diagnosed with schizophrenia born since 1955. They also drew data on healthy controls (n=176,956) using the Danish Civil Registration System. The sample was followed until a diagnosis of digestive disorders, death, or April 10, 2017.

The primary outcome was incident of digestive organ disorders, including cancers of the digestive organs, IBD, and disorders of gut-brain interaction (ie, functional gastrointestinal disorders, irritable bowel syndrome, dyspepsia). The researchers used models of stratified Cox regression to examine the role of cannabis use in the risk of digestive organ disorders in people with schizophrenia vs people without schizophrenia. A fully adjusted model accounted for CUD, alcohol use disorders, and other substance use disorders as time-varying variables.

Patients with schizophrenia were more likely to develop all of the examined disorders of the digestive organs with the exclusion of cancers and disorders of the pancreas and liver. CUD alongside schizophrenia was significantly associated with decreased risk of disorders of gut-brain interaction (hazard ratio [HR], 0.84; 95% CI 0.74-0.94, P =.003) and a nonsignificant trend toward decreased IBD (HR, 0.71, 95% CI 0.48-1.03, P =.07) in the fully adjusted model. In addition, patients with schizophrenia and CUD had a lower risk of serious digestive disorders (HR, 0.89; 95% CI, 0.77-1.02; P =.09).

The researchers further examined absolute risk for developing disorders of gut-brain interaction and IBD by age 60 using the fully adjusted Cox curves. In the schizophrenia cohort, the risk for developing disorders of gut-brain interactions in cases without CUD was 23.0% compared with a 17.8% risk in cases with CUD. For controls, the corresponding risks were 14.0% and 17.1%, respectively. The risk of developing IBD in cases with schizophrenia was 3.4% in the absence of CUD and 2.4% with CUD. For controls, the corresponding risks were 2.9% and 3.5%, respectively.

The study is limited by the inability to determine a potential dose-dependent response to cannabis. Other limitations included the absence of antipsychotic medication use as a variable and potential difficulty in generalizing results to non-European populations.

“The endocannabinoid system disruptions seen in schizophrenia, possibly mediated through use of antipsychotics, may thus be at least partially countered by use of cannabis, alleviating the increased risk of disorders of the digestive organs otherwise associated with schizophrenia,” the researchers noted.

References

1.  Olesen JA, Posselt CM, Poulsen CH, Nordentoft M, Hjorthøj C. Cannabis use disorders may protect against certain disorders of the digestive organs in people with schizophrenia but not in healthy controls. Psychol Med. 2020;50(3):499-506.

2.  Hjorthøj C, Østergaard ML, Benros ME, et al. Association between alcohol and substance use disorders and all-cause and cause-specific mortality in schizophrenia, bipolar disorder, and unipolar depression: a nationwide, prospective, register-based study. Lancet Psychiatry. 2015;2(9):801-808.