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Cannabinoid-Related Acute Pancreatitis: An Update from International Literature and Individual Case Safety Reports

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Abstract

Introduction

In addition to the growing interest of different cannabinoids for therapeutic purposes, the safety profile of these substances has changed, with the recent identification of new events such as acute pancreatitis.

Objective

The aim of this study was to characterize cannabinoid-related acute pancreatitis, based on the recent literature and the analysis of pharmacovigilance data available worldwide.

Methods

Nine national and international pharmacovigilance databases were requested for individual case safety reports of acute pancreatitis related to cannabinoid exposure. A systematic review was performed searching in PubMed®, Web of Science®, and Google Scholar® for any publication dealing with acute pancreatitis and cannabinoid exposure (cannabis, cannabinoid, cannabidiol, tetrahydrocannabinol, nabilone, dronabinol), to identify case reports, observational studies, clinical trials, or reviews. All queries were updated on 1 January, 2021.

Results

Twenty-two individual case safety reports were identified in the pharmacovigilance databases and 51 in the literature, corresponding to a predominantly young male population (74% of men, median age 28 interquartile range [21–39]) using recreational Cannabis sativa with high intensity. A therapeutic purpose was identified in 13 cases (including tetrahydrocannabinol, cannabidiol, and dronabinol). The outcome was often favorable after dechallenge (except three deaths), and frequent recurrences were observed in the case of rechallenge or sustained consumption. Eleven cross-sectional studies and one ecological study showed an increasing trend of cannabis use in in-patients with acute pancreatitis, with a significantly lower in-hospital mortality.

Conclusions

This review underlines that acute pancreatitis is a potential adverse effect of cannabinoid use. It remains often unrecognized and can occur during recreational or therapeutic use. The development of the therapeutic use of cannabinoids in frail patients deserves a better investigation of the benefit-risk ratio of these different products.

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References

  1. EMCDDA. European drug report 2019: trends and developments. Lisbon: EMCDDA; 2019.

    Google Scholar 

  2. Goodman S, Wadsworth E, Leos-Toro C, Hammond D, International Cannabis Policy Study Team. Prevalence and forms of cannabis use in legal vs. illegal recreational cannabis markets. Int J Drug Policy. 2020;76:102658.

    PubMed  Google Scholar 

  3. Bouquet E, Pain S, Eiden C, Jouanjus E, Richard N, Fauconneau B, French Addictovigilance Network, et al. Adverse events of recreational cannabis use reported to the French addictovigilance network (2012–2017). Br J Clin Pharmacol. 2021;87(10):3925–37.

    CAS  PubMed  Google Scholar 

  4. Meczker A, Hanak L, Parniczky A, Szentesi A, Eross B, Hegyi P, et al. Analysis of 1060 cases of drug-induced acute pancreatitis. Gastroenterology. 2020;159(5):1958–61.

    PubMed  Google Scholar 

  5. Vivian E, Cler L, Conwell D, Cote GA, Dickerman R, Freeman M, et al. Acute Pancreatitis Task Force on Quality: development of quality indicators for acute pancreatitis management. Am J Gastroenterol. 2019;114(8):1322–42.

    PubMed  Google Scholar 

  6. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021;10(1):89.

    PubMed  PubMed Central  Google Scholar 

  7. Fouretier A, Malriq A, Bertram D. Open access pharmacovigilance databases: analysis of 11 databases. Pharm Med. 2016;30(4):221–31.

    CAS  Google Scholar 

  8. Berbain T, Pariente A, Miremont-Salamé G, Grandvuillemin A, Micallef J, Chouchana L, et al. Contribution of causality assessment for an automated detection of safety signals: an example using the French Pharmacovigilance Database. Drug Saf. 2020;43(3):243–53.

    PubMed  Google Scholar 

  9. Lindquist M. VigiBase, the WHO global ICSR database system: basic facts. Drug Inf J. 2008;42(5):409–19.

    Google Scholar 

  10. Aach RA. Acute-pancreatitis after marijuana smoking: is there a relationship. JAMA 1985. 1985;253(12):1791.

    Google Scholar 

  11. Grant P, Gandhi P. A case of cannabis-induced pancreatitis. J Pancreas. 2004;5(1):41–3.

    Google Scholar 

  12. Bournet B, Buscail L. Cannabis: a rare cause of acute pancreatitis. Gastroenterol Clin Biol. 2008;32(11):922–3.

    CAS  PubMed  Google Scholar 

  13. Lingutla D, Rohatgi A, Li J, Sorrentino S, DiSalle M, Leschingski R. Cannabis induced pancreatitis. Am J Gastroenterol. 2009;104:S236–7.

    Google Scholar 

  14. Belze O Jr, Legras A, Ehrmann S, Garot D, Perrotin D. Cannabis-induced acute pancreatitis. Am J Emerg Med. 2011;29(1):131.e3-4.

    Google Scholar 

  15. Safsaf H, Stirnemann J, Maire F, Fain O. Pancréatite aiguë au cannabis: une étiologie classique ? Rev Med Interne. 2011;32:S376–7.

    Google Scholar 

  16. Zayouna N, Dudar A, Iskanderian Z, Stawick L, Ahsan S. Acute pancreatitis secondary to marijuana use. Am J Gastroenterol. 2012;107:S339.

    Google Scholar 

  17. Howaizi M, Chahine M, Haydar F, Jemaa Y, Lapoile E. Cannabis-induced recurrent acute pancreatitis. Acta Gastroenterol Belg. 2012;75(4):446–7.

    PubMed  Google Scholar 

  18. Fatma H, Mouna B, Leila M, Radhouane D, Taoufik N. Cannabis: a rare cause of acute pancreatitis. Clin Res Hepatol Gastroenterol. 2013;37(1):e24–5.

    PubMed  Google Scholar 

  19. Jalal T, Ramchandani H. Cannabis abuse: a rare cause of acute pancreatitis. J Gen Intern Med. 2013;28;S304.

    Google Scholar 

  20. Kayar Y, Eroglu H, Pamukcu O, Cetin H, Kocas O, Atci M. Cannabinoid-induced acute pancreatitis. Turk J Gastroenterol. 2014;25(3):335–6.

    PubMed  Google Scholar 

  21. Akkucuk MH, Erbayrak M. A rare and unexpected side-effect of cannabis use: abdominal pain due to acute pancreatitis. Case Rep Emerg Med. 2015. https://doi.org/10.1155/2015/463836.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gino M, Mete F. A rare case of acute pancreatitis. Italian J Med. 2015;9(S2):47.

    Google Scholar 

  23. Lorvellec A, Thiriet L, Andrianjafy C, Gervaise A, Seigne AL, Rey P. Recurrent cannabis-induced acute pancreatitis. Presse Medicale. 2015;44(4 Pt 1):468–71.

    Google Scholar 

  24. Nayak SK, Preethi M, Zanwar S, Palaniswamy KR. Cannabis induced recurrent acute pancreatitis. Trop Doct. 2016;46(4):238–9.

    PubMed  Google Scholar 

  25. Espino García A, Jorge Tufet C, Lafarga Giribets MA, Justribó Sánchez ME, Carré GG. Cannabis-induced pancreatitis. SEMERGEN. 2016;42(2):123–4.

    PubMed  Google Scholar 

  26. Herrero LN, Chaucer B, Singh S, Deshpande V, Patel SH. Acute pancreatitis secondary to marijuana consumption. J Pancreas. 2016;17(3):322–3.

    Google Scholar 

  27. Tripathi N, Koirala N. Cannabinoid induced pancreatitis: a case report and literature review. J Gen Emerg Med. 2017;2(5):1–4.

    Google Scholar 

  28. Basnyat S, Patel M, Irfan H, Nandish B, Steinberger D. An unusual case of marijuana induced acute pancreatitis. Chest. 2018;154(4):331a.

    Google Scholar 

  29. Szurnicki P, Alansari A, Alansari T, Khan G. Cannabis as an overlooked cause of acute pancreatitis: a case report and literature review: 1383. Am J Gastroenterol. 2018;113:S794.

    Google Scholar 

  30. Ghazaleh S, Alqahtani A, Nehme C, Abugharbyeh A, Said Ahmed TS. A rare case of cannabis-induced acute pancreatitis. Cureus. 2019;11(6):e4878.

    PubMed  PubMed Central  Google Scholar 

  31. Pagliari D, Saviano A, Brizi MG, Mancarella FA, Cannone F, Musso M, et al. Cannabis-induced acute pancreatitis: a case report with comprehensive literature review. Eur Rev Med Pharmacol Sci. 2019;23(19):8625–9.

    CAS  PubMed  Google Scholar 

  32. Chandy J, Hassan A, Sciarra M. “HASH”ing out pancreatitis: the new increasingly common culprit. J Community Hosp Intern Med Perspect. 2019;9(4):360–1.

    PubMed  PubMed Central  Google Scholar 

  33. John J, Gandhi S, Nam D, Niakan L. A case of cannabis-induced acute pancreatitis. Cureus. 2019;11(9):e5754.

    PubMed  PubMed Central  Google Scholar 

  34. Hutflesz C, Parihar V. Clinical innovation poster abstracts: medical cannabis induced acute pancreatitis and hyperemesis syndrome in a patient with a complex regional pain syndrome. Can J Pain. 2019;3(1):A50-72.

    Google Scholar 

  35. Ahuja AC, Aijazi M. Severe acute pancreatitis secondary to topical cannabinoid use: 3031. Am J Gastroenterol. 2019;114(2019 ACG Annual Meeting Abstracts):1637.

    Google Scholar 

  36. Osueni A, Osueni GI, Mbamalu DC, Owoseni O, Nemakallu SR. A smoked-out pancreas: an unusual case of acute pancreatitis. Am J Gastroenterol. 2020;115:S1742–3.

    Google Scholar 

  37. Singh R, Torre K, Saba M, Stepczynski J. Cannabis-induced pancreatitis: a new clinical entity. Pancreas. 2020;49(7):e66–7.

    PubMed  Google Scholar 

  38. Wargo KA, Geveden BN, McConnell VJ. Cannabinoid-induced pancreatitis: a case series. J Pancreas. 2007;8(5):579–83.

    Google Scholar 

  39. Culetto A, Bournet B, Haennig A, Alric L, Peron JM, Buscail L. Prospective evaluation of the aetiological profile of acute pancreatitis in young adult patients. Digest Liver Dis. 2015;47(7):584–9.

    Google Scholar 

  40. Culetto A, Bournet B, Buscail L. Clinical profile of cannabis-associated acute pancreatitis. Digest Liver Dis. 2017;49(11):1284–5.

    Google Scholar 

  41. Mikolašević I, Milić S, Mijandrušić-Sinčić B, Licul V, Štimac D. Cannabis-induced acute pancreatitis. Med Glas. 2013;10(2):405–7.

    Google Scholar 

  42. Chadalavada P, Simons-Linares CR, Chahal P. Drug-induced acute pancreatitis: prevalence, causative agents, and outcomes. Pancreatology. 2020;20(7):1281–6.

    CAS  PubMed  Google Scholar 

  43. Hutflesz C, Parihar V. Medical cannabis induced acute pancreatitis and hyperemesis syndrome in a patient with complex regional pain syndrome. Can J Pain. 2019;3(1): A71.

    Google Scholar 

  44. Goyal H, Guerreso K, Smith B, Harper K, Patel S, Patel A, et al. Severity and outcomes of acute alcoholic pancreatitis in cannabis users. Transl Gastroenterol Hepatol. 2017;2:60.

    PubMed  PubMed Central  Google Scholar 

  45. Goyal H, Desai R, Patel U, Perisetti A, Chhabra R. Outcomes of acute pancreatitis treatment in the cannabis users: a nationwide propensity matched analysis. Am J Gastroenterol. 2018;113:S51-S.

    Google Scholar 

  46. Njei B, McCarty TR, Sharma P, Singh M, Haque L, Aslanian H, et al. Cannabis use disorder is associated with increased risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis: analysis of the U.S. Nationwide Inpatient Sample (NIS) Database, 2004–2014. ACG. 2017;112:S19.

    Google Scholar 

  47. Njei B, Sharma P, McCarty TR, Singh M, Haque L, Aslanian HR, et al. Cannabis use is associated with increased risk of post–endoscopic retrograde cholangiopancreatography pancreatitis: analysis of the US nationwide inpatient sample database, 2004–2014. Pancreas. 2018;47(9):1142–9.

    CAS  PubMed  Google Scholar 

  48. Simons-Linares CR, Barkin JA, Wang Y, Jaiswal P, Trick W, Bartel MJ, et al. Is there an effect of cannabis consumption on acute pancreatitis? Dig Dis Sci. 2018;63(10):2786–91.

    PubMed  Google Scholar 

  49. Adejumo AC, Akanbi O, Adejumo KL, Bukong TN. Reduced risk of alcohol-induced pancreatitis with cannabis use. Alcohol Clin Exp Res. 2019;43(2):277–86.

    CAS  PubMed  Google Scholar 

  50. Enofe I, Igenoza O, Osaghae O, Rai M, Aluko A, Laird-Fick H. Prevalence of acute pancreatitis among cannabis users: review of the National Inpatient Sample database. HPB. 2019;21:S118–9.

    Google Scholar 

  51. Nemer L, Hinton A, Krishna S, Conwell D, Lara L. 31 The relationship between acute pancreatitis and cannabis use before and after recreational legalization in select States. ACG. 2019;114:S19.

    Google Scholar 

  52. Salazar M, Abou Saleh M, Barkin JA, Elkhouly MA, Mansoor E, Barkin JS, et al. 29 cannabis use is associated with worse outcomes in acute pancreatitis: analysis of a large database. ACG. 2019;114:S16–8.

    Google Scholar 

  53. Salazar M, Barkin JA, Ramey JS, Kumapley R, Paintsil I, Barkin JS, et al. 20 comparison and outcomes of cannabis users with acute pancreatitis according to severity using the Revised Atlanta Classification of Acute Pancreatitis. ACG. 2019;114:S11.

    Google Scholar 

  54. Salazar M, Ramey JS, Barkin JA, Kumapley R, Paintsil I, Barkin JS, et al. 19 outcomes of acute necrotizing pancreatitis and associated fluid collections in cannabis users. ACG. 2019;114:S11.

    Google Scholar 

  55. Saleem S, Then EO, Abu-Heija A, Weissman S, Gaduputi V. 22 association between acute pancreatitis and cannabis use: a US population-based study. ACG. 2019;114:S12–3.

    Google Scholar 

  56. Sarmini MT. Evaluation of acute pancreatitis and cannabis use association and outcomes: a cross sectional study using large inpatient data. Eur J Biomed. 2019;6(7):72–7.

    CAS  Google Scholar 

  57. Simons-Linares CR, Barkin JA, Jang S, Bhatt A, Lopez R, Stevens T, et al. The impact of cannabis consumption on mortality, morbidity, and cost in acute pancreatitis patients in the United States: a 10-year analysis of the National Inpatient Sample. Pancreas. 2019;48(6):850–5.

    PubMed  Google Scholar 

  58. Bolourani S, Diao L, Thompson DA, Wang P, Coppa GF, Patel VM, et al. Risk factors for early readmission after acute pancreatitis: importance of timely interventions. J Surg Res. 2020;252:96–106.

    PubMed  Google Scholar 

  59. Barkin JA, Nemeth Z, Saluja AK, Barkin JS. Cannabis-induced acute pancreatitis: a systematic review. Pancreas. 2017;46(8):1035–8.

    PubMed  Google Scholar 

  60. Buscail L, Le Cosquer G, Gilletta C, Bournet B, Culetto A. Cannabis et pancréatite aiguë. La Presse Méd Formation. 2020;1(4):373–7.

    Google Scholar 

  61. Sagaram M, Sundar P, Reddy S. S0021Cannabis-induced acute pancreatitis: a systematic review. Am J Gastroenterol. 2020;115(1):S10-S.

    Google Scholar 

  62. Weissman S, Aziz M, Perumpail RB, Mehta TI, Patel R, Tabibian JH. Ever-increasing diversity of drug-induced pancreatitis. World J Gastroenterol. 2020;26(22):2902–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Kim J, Lee KJ, Kim JS, Rho JG, Shin JJ, Song WK, et al. Cannabinoids regulate Bcl-2 and cyclin D2 expression in pancreatic beta cells. PLoS ONE. 2016;11(3):e0150981.

    PubMed  PubMed Central  Google Scholar 

  64. Kim W, Lao Q, Shin YK, Carlson OD, Lee EK, Gorospe M, et al. Cannabinoids induce pancreatic beta-cell death by directly inhibiting insulin receptor activation. Sci Signal. 2012;5(216):ra23.

    PubMed  PubMed Central  Google Scholar 

  65. Gotfried J, Naftali T, Schey R. Role of cannabis and its derivatives in gastrointestinal and hepatic disease. Gastroenterology. 2020;159(1):62–80.

    CAS  PubMed  Google Scholar 

  66. Zyromski NJ, Mathur A, Wade T, Wang S, Swartz-Basile DA, Prather A, et al. Cannabinoid receptor blockade attenuates acute pancreatitis by an adiponectin mediated mechanism. Gastroenterology. 2008;134(4):A876-A.

    Google Scholar 

  67. Van Rafelghem B, Covaci A, Anseeuw K, van Nuijs ALN, Neels H, Mahieu B, et al. Suicide by vaping the synthetic cannabinoid 4F-MDMB-BINACA: cannabinoid receptors and fluoride at the crossroads of toxicity? Forensic Sci Med Pathol. 2021;17: 684–688.

    PubMed  Google Scholar 

  68. de Almeida DL, Devi LA. Diversity of molecular targets and signaling pathways for CBD. Pharmacol Res Perspect. 2020;8(6):e00682.

    PubMed  PubMed Central  Google Scholar 

  69. Utomo WK, de Vries M, van Rijckevorsel DC, Peppelenbosch MP, van Goor H, Fuhler GM. Cannabinoid receptor agonist namisol does not affect cytokine levels in chronic pancreatitis patients. Am J Gastroenterol. 2015;110(8):1244–5.

    CAS  PubMed  Google Scholar 

  70. de Vries M, Van Rijckevorsel DC, Vissers KC, Wilder-Smith OH, Van Goor H. Single dose delta-9-tetrahydrocannabinol in chronic pancreatitis patients: analgesic efficacy, pharmacokinetics and tolerability. Br J Clin Pharmacol. 2016;81(3):525–37.

    PubMed  PubMed Central  Google Scholar 

  71. Charilaou P, Agnihotri K, Garcia P, Badheka A, Frenia D, Yegneswaran B. Trends of cannabis use disorder in the inpatient: 2002 to 2011. Am J Med. 2017;130(6):678-87.e7.

    PubMed  Google Scholar 

  72. Lara LF, Nemer L, Hinton A, Balasubramanian G, Conwell DL, Krishna S. Acute and severe acute pancreatitis and the effect of cannabis in States before and after legalization compared with States without legalized cannabis. Pancreas. 2021;50(5):766–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Han B, Gfroerer JC, Colliver JD. Associations between duration of illicit drug use and health conditions: results from the 2005–2007 national surveys on drug use and health. Ann Epidemiol. 2010;20(4):289–97.

    PubMed  Google Scholar 

  74. Lafaurie M, Pochard L, Lotiron C, Molinier L, Lapeyre-Mestre M, Jouanjus E. Identification of somatic disorders related to psychoactive drug use from an inpatient database in a French University Hospital. Clin Drug Investig. 2018;38(10):977–82.

    PubMed  Google Scholar 

  75. Bhandari R, Gupta S, Modi K, Raval MR, Joundi H, Patel JR, et al. Persistent cannabis abuse and risk for hospitalization for acute pancreatitis: a cross-sectional study in United States hospitals. Cureus. 2021;13(6):e15601.

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, CIC 1436, CHU, Université de Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France

    Camille Azam & Maryse Lapeyre-Mestre

  2. Service de Gastroentérologie et Pancréatologie, CIC Biotherapies 1436, CHU, Université de Toulouse, Toulouse, France

    Louis Buscail

  3. Service de Gastroentérologie et Pancréatologie, CHU, Université de Toulouse, Toulouse, France

    Adrian Culetto

Authors
  1. Camille Azam
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  2. Louis Buscail
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  3. Adrian Culetto
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  4. Maryse Lapeyre-Mestre
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Corresponding author

Correspondence to Maryse Lapeyre-Mestre.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This work has been conducted in the context of a research master training of Camille Azam at the University of Toulouse.

Conflicts of interest/Competing interests

Camille Azam, Adrian Culetto, and Maryse Lapeyre-Mestre declare that they have no conflict of interest. Louis Buscail has received research grants from CVASTHERA pharmaceutical.

Ethics approval

This study did not required any specific ethics approval, case reports included have been already published in the scientific literature, or are accessible through open or restricted national or international pharmacovigilance databases.

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Not applicable.

Consent for publication

Not applicable.

Availability of data and material

As indicated in the article, data extracted from the open pharmacovigilance databases can be extracted by any individual. Information from databases with a restricted access can be obtained on request from the Uppsala Monitoring Center and/or from national pharmacovigilance centers. All data used and generated in the literature review are presented in the main text of the article or in the ESM. All literature cases are available as published on request.

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Authors’ contributions

MLM had the idea for the article, CA and MLM performed the literature search, data extraction and data analysis, and the pharmacovigilance database search, LB and EC provided their list of references and published case series, CA drafted the first draft, and all authors revised the work and approved the final manuscript.

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Azam, C., Buscail, L., Culetto, A. et al. Cannabinoid-Related Acute Pancreatitis: An Update from International Literature and Individual Case Safety Reports. Drug Saf 45, 215–235 (2022). https://doi.org/10.1007/s40264-022-01146-7

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