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Cannabis use disorders may protect against certain disorders of the digestive organs in people with schizophrenia but not in healthy controls

Published online by Cambridge University Press:  18 March 2019

Julie Aamand Olesen ,
Christine Merrild Posselt ,
Chalotte Heinsvig Poulsen ,
Merete Nordentoft  and
Carsten Hjorthøj Open the ORCID record for Carsten Hjorthøj [Opens in a new window]
Julie Aamand Olesen
Affiliation:
Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPsych, Aarhus and Copenhagen, Denmark University of Copenhagen, The Research Unit for General Practice, Copenhagen, Denmark
Christine Merrild Posselt
Affiliation:
Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPsych, Aarhus and Copenhagen, Denmark
Chalotte Heinsvig Poulsen
Affiliation:
Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPsych, Aarhus and Copenhagen, Denmark
Merete Nordentoft
Affiliation:
Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPsych, Aarhus and Copenhagen, Denmark
Carsten Hjorthøj*
Affiliation:
Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPsych, Aarhus and Copenhagen, Denmark Department of Public Health, University of Copenhagen, Section of Epidemiology, Copenhagen, Denmark
*
Author for correspondence: C. Hjorthøj, E-mail: carsten.hjorthoej@regionh.dk
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Abstract

Background. Previous studies have shown a potential for cannabis in disorders of the digestive organs. We aimed to investigate whether cannabis use disorders (CUD) would decrease the risk of incident disorders of the digestive organs, in people with schizophrenia and population controls.

Methods. We combined nationwide Danish registers to identify 21 066 cases with schizophrenia and 176 935 sex-and-age-matched controls. Two models were analyzed for the associations between CUD and digestive disorders in time-varying Cox regressions: one adjusted for sex, year of birth, and calendar year; and one further adjusted for alcohol and other substance use disorders and parental education.

Results. CUD was associated with a decreased risk of developing disorders of gut–brain interaction (e.g. irritable bowel syndrome, dyspepsia, etc.) among cases with schizophrenia (HR = 0.84, 95% CI 0.74–0.94, p = 0.003). CUD was associated with decreased risk of inflammatory bowel disease (HR = 0.70, 95% CI 0.49–0.99, p = 0.045) in the basically adjusted model, dropping just below statistical significance in the fully adjusted model (HR = 0.71, 95% CI 0.48–1.03, p = 0.07). CUD displayed a tendency toward a decreased risk of serious disorders of the digestive organs among cases with schizophrenia (HR = 0.89, 95% CI 0.77–1.02, p = 0.09) in the fully adjusted model. No associations were observed among controls.

Conclusions. In people with schizophrenia, but not in controls, CUD is associated with decreased risk of disorders of gut–brain interaction and inflammatory bowel disease, and possibly other serious disorders of the digestive organs. Our findings could lead to new targets for treatment and prevention of disorders of the digestive organs.

Keywords

CannabinoidsCannabisdigestive organsgastro-intestinalgut–brain axisinflammatory bowel diseasepsychosis
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 3 , February 2020 , pp. 499 - 506
Copyright
Copyright © Cambridge University Press 2019

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References

Agrawal, A, Budney, AJ and Lynskey, MT (2012) The co-occurring use and misuse of cannabis and tobacco: a review. Addiction 107, 1221–1233.CrossRefGoogle ScholarPubMed
Alhouayek, M and Muccioli, GG (2012) The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity. Trends in Molecular Medicine 18, 615–625.CrossRefGoogle ScholarPubMed
Australian Institute of Health & Welfare (2016) National Drug Strategy Household Survey 2016. Drug statistics series.Google Scholar
Benros, ME, Pedersen, MG, Rasmussen, H, Eaton, WW, Nordentoft, M and Mortensen, PB (2014) A nationwide study on the risk of autoimmune diseases in individuals with a personal or a family history of schizophrenia and related psychosis. American Journal of Psychiatry 171, 218–226.CrossRefGoogle ScholarPubMed
Bermudez, A, Visina, J and Walker, L (2017). Differential effects of cannabinoid receptor stimulation in smooth muscle. The FASEB Journal 31, (Suppl. 1), Abstract No: 690.4.Google Scholar
Covey, DP, Mateo, Y, Sulzer, D, Cheer, JF and Lovinger, DM (2017) Endocannabinoid modulation of dopamine neurotransmission. Neuropharmacology 124, 52–61.CrossRefGoogle ScholarPubMed
Danielsson, AK, Lundin, A, Yaregal, A, Östenson, CG, Allebeck, P and Agardh, EE (2016) Cannabis use as risk or protection for type 2 diabetes: a longitudinal study of 18 000 Swedish men and women. Journal of Diabetes Research 2016, 1–6.CrossRefGoogle ScholarPubMed
Ellulu, MS, Patimah, I, Khaza'ai, H, Rahmat, A and Abed, Y (2017) Obesity and inflammation: the linking mechanism and the complications. Archives of Medical Science 4, 851–863.CrossRefGoogle Scholar
European Monitoring Centre for Drugs and Drug Addiction (2016) European Drug Report 2016: Trends and Developments. European Monitoring of Drugs and Drugs Addiction.Google Scholar
Fabisiak, A and Fichna, J (2017) Cannabinoids as gastrointestinal anti-inflammatory drugs. Neurogastroenterology and Motility 29, e13038.CrossRefGoogle ScholarPubMed
Fakhoury, M (2017) Role of the endocannabinoid system in the pathophysiology of schizophrenia. Molecular Neurobiology 54, 768–778.CrossRefGoogle ScholarPubMed
Galli, JA, Sawaya, RA and Friedenberg, FK (2011) Cannabinoid hyperemesis syndrome. Current Drug Abuse Reviews 4, 241–249.CrossRefGoogle ScholarPubMed
Goyal, H, Singla, U, Gupta, U and May, E (2017) Role of cannabis in digestive disorders. European Journal of Gastroenterology & Hepatology 29, 135–143.CrossRefGoogle ScholarPubMed
Green, B, Young, R and Kavanagh, D (2005) Cannabis use and misuse prevalence among people with psychosis. British Journal of Psychiatry 187, 306–313.CrossRefGoogle ScholarPubMed
Gupta, S, Masand, PS, Kaplan, D, Bhandary, A and Hendricksa, S (1997) The relationship between schizophrenia and irritable bowel syndrome (IBS). Schizophrenia Research 23, 265–268.CrossRefGoogle Scholar
Han, B, Gfroerer, JC and Colliver, JD (2010) Associations between duration of illicit drug Use and health conditions: results from the 2005–2007 national surveys on drug Use and health. Annals of Epidemiology 20, 289–297.CrossRefGoogle ScholarPubMed
Hézode, C, Roudot-Thoraval, F, Nguyen, S, Grenard, P, Julien, B, Zafrani, E-S, Pawlostky, J-M, Dhumeaux, D, Lotersztajn, S and Mallat, A (2005) Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology 42, 63–71.CrossRefGoogle ScholarPubMed
Hézode, C, Zafrani, ES, Roudot-Thoraval, F, Costentin, C, Hessami, A, Bouvier-Alias, M, Medkour, F, Pawlostky, JM and Lotersztajn, SMA (2008) Daily cannabis use: a novel risk factor of steatosis severity in patients with chronic hepatitis C. Gastroenterology 134, 432–439.CrossRefGoogle ScholarPubMed
Hjorthøj, C, Østergaard, MLD, Benros, ME, Toftdahl, NG, Erlangsen, A, Andersen, JT and Nordentoft, M (2015) 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. The Lancet Psychiatry 2, 801–808.CrossRefGoogle ScholarPubMed
Jin, LZ, Rangan, A, Mehlsen, J, Andersen, LB, Larsen, SC and Heitmann, BL (2017) Association between use of Cannabis in adolescence and weight change into midlife. PLoS ONE 12, e0168897.CrossRefGoogle ScholarPubMed
Jørgensen, KB, Nordentoft, M and Hjorthøj, C (2018) Association between alcohol and substance use disorders and psychiatric service use in patients with severe mental illness: a nationwide Danish register-based cohort study. Psychological Medicine 48, 1–9.CrossRefGoogle ScholarPubMed
Kafil, TS, Nguyen, TM, MacDonald, JK and Chande, N (2018 a) Cannabis for the treatment of Crohn's disease. Cochrane Database of Systematic Reviews, issue 11.CrossRefGoogle ScholarPubMed
Kafil, TS, Nguyen, TM, MacDonald, JK, and Chande, N (2018 b) Cannabis for the treatment of ulcerative colitis. Cochrane Database of Systematic Reviews, issue 11.CrossRefGoogle ScholarPubMed
Kildemoes, HW, Sørensen, HT, Hallas, J, Sorensen, HT and Hallas, J (2011) The Danish National Prescription Registry. Scandinavian Journal of Public Health 39, 38–41.CrossRefGoogle ScholarPubMed
Large, M, Mullin, K, Gupta, P, Harris, A and Nielssen, O (2014) Systematic meta-analysis of outcomes associated with psychosis and co-morbid substance use. Australian & New Zealand Journal of Psychiatry 48, 418–432.CrossRefGoogle ScholarPubMed
Ligresti, A, De Petrocellis, L and Di Marzo, V (2016) From phytocannabinoids to cannabinoid receptors and endocannabinoids: pleiotropic physiological and pathological roles through complex pharmacology. Physiological Reviews 96, 1593–1659.CrossRefGoogle ScholarPubMed
Lu, H-C and Mackie, K (2016) An introduction to the endogenous cannabinoid system. Biological Psychiatry 79, 516–525.CrossRefGoogle ScholarPubMed
Lynge, E, Sandegaard, JL and Rebolj, M (2011) The Danish National Patient Register. Scandinavian Journal of Public Health 39, 30–33.CrossRefGoogle ScholarPubMed
Mallat, A, Hezode, C and Lotersztajn, S (2008) Environmental factors as disease accelerators during chronic hepatitis C. Journal of Hepatology 48, 657–665.CrossRefGoogle ScholarPubMed
Massa, F, Storr, M and Lutz, B (2005) The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. Journal of Molecular Medicine 83, 944–954.CrossRefGoogle ScholarPubMed
McPartland, JM, Guy, GW and Di Marzo, V (2014) Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system. PLoS ONE 9.CrossRefGoogle ScholarPubMed
Meier, MH, Caspi, A, Ambler, A, Harrington, H, Houts, R, Keefe, RSE, McDonald, K, Ward, A, Poulton, R and Moffitt, TE (2012) Persistent cannabis users show neuropsychological decline from childhood to midlife. Proceedings of the National Academy of Sciences 109, E2657–E2664.CrossRefGoogle ScholarPubMed
Monteiro, R and Azevedo, I (2010) Chronic inflammation in obesity and the metabolic syndrome. Mediators of Inflammation 2010, 1–10.CrossRefGoogle ScholarPubMed
Mors, O, Perto, GP and Mortensen, PB (2011) The Danish Psychiatric Central Research Register. Scandinavian Journal of Public Health 39, 54–57.CrossRefGoogle ScholarPubMed
Ngueta, G, Bélanger, RE, Laouan-Sidi, EA and Lucas, M (2015) Cannabis use in relation to obesity and insulin resistance in the inuit population. Obesity 23, 290–295.CrossRefGoogle ScholarPubMed
Ozdemir, V, Jamal, MM, Osapay, K, Jadus, MR, Sandor, Z, Hashemzadeh, M and Szabo, S (2007) Cosegregation of gastrointestinal ulcers and schizophrenia in a large national inpatient discharge database. Journal of Investigative Medicine 55, 315–320.CrossRefGoogle Scholar
Pandey, R, Mousawy, K, Nagarkatti, M and Nagarkatti, P (2009) Endocannabinoids and immune regulation. Pharmacological Research 60, 85–92.CrossRefGoogle ScholarPubMed
Pedersen, CB (2011) The Danish Civil Registration System. Scandinavian Journal of Public Health 39, 22–25.CrossRefGoogle ScholarPubMed
Pedersen, CB, Gøtzsche, H, Møller, JØO and Mortensen, PB (2006) The Danish Civil Registration System A cohort of eight million persons. National Centre for Register-Based Research, University of Aarhus, Taasingegade 1, 8000 Aarhus C, Denmark. . Danish Medical Bulletin 53, 441–449.Google ScholarPubMed
Pertwee, RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9 –tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. British Journal of Pharmacology 153, 199–215.CrossRefGoogle ScholarPubMed
Petersson, F, Baadsgaard, M and Thygesen, LC (2011) Danish registers on personal labour market affiliation. Scandinavian Journal of Public Health 39, 95–98.CrossRefGoogle ScholarPubMed
Roberts, L, Roalfe, A, Wilson, S and Lester, H (2006) Physical health care of patients with schizophrenia in primary care: a comparative study. Family Practice 24, 34–40.CrossRefGoogle ScholarPubMed
Scheffler, F, Kilian, S, Chiliza, B, Asmal, L, Phahladira, L, du Plessis, S, Kidd, M, Murray, RM, Di Forti, M, Seedat, S and Emsley, R (2018) Effects of cannabis use on body mass, fasting glucose and lipids during the first 12 months of treatment in schizophrenia spectrum disorders. Schizophrenia Research 199, 90–95.CrossRefGoogle Scholar
Schlicker, E and Kathmann, M (2001) Modulation of transmitter release via presynaptic cannabinoid receptors. TRENDS in Pharmacological Sciences 22, 565–572.CrossRefGoogle ScholarPubMed
Storr, M, Devlin, S, Kaplan, GG, Panaccione, R and Andrews, CN (2014) Cannabis use provides symptom relief in patients with inflammatory bowel disease but is associated with worse disease prognosis in patients with Crohn's disease. Inflammatory Bowel Diseases 20, 472–480.CrossRefGoogle ScholarPubMed
Straiker, A, Dvorakova, M, Zimmowitch, A and Mackie, K (2018) Cannabidiol inhibits endocannabinoid signaling in autaptic hippocampal neurons. Molecular Pharmacology 94, 743–748.CrossRefGoogle ScholarPubMed
Thomas, GA, Rhodes, J and Ingram, JR (2005) Mechanisms of disease: nicotine – a review of its actions in the context of gastrointestinal disease. Nature Clinical Practice Gastroenterology & Hepatology 2, 536–544.CrossRefGoogle ScholarPubMed
Toftdahl, NG, Nordentoft, M and Hjorthøj, C (2016) Prevalence of substance use disorders in psychiatric patients: a nationwide Danish population-based study. Social Psychiatry and Psychiatric Epidemiology 51, 129–140.CrossRefGoogle ScholarPubMed
Verschuere, S, De Smet, R, Allais, L and Cuvelier, CA (2012) The effect of smoking on intestinal inflammation: what can be learned from animal models? Journal of Crohn's and Colitis 6, 1–12.CrossRefGoogle ScholarPubMed
Wobrock, T, Falkai, P, Schneider-Axmann, T, Hasan, A, Galderisi, S, Davidson, M, Kahn, RS, Derks, EM, Boter, H, Rybakowski, JK, Libiger, J, Dollfus, S, López-Ibor, JJ, Peuskens, J, Hranov, LG, Gaebel, W and Fleischhacker, WW (2013) Comorbid substance abuse in first-episode schizophrenia: effects on cognition and psychopathology in the EUFEST study. Schizophrenia Research 147, 132–139.CrossRefGoogle ScholarPubMed