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Low-Dose Cannabidiol Is Safe but Not Effective in the Treatment for Crohn’s Disease, a Randomized Controlled Trial

Digestive Diseases and Sciences volume 62, pages 1615–1620 (2017)Cite this article

Abstract

Background

Cannabidiol (CBD) is an anti-inflammatory cannabinoid shown to be beneficial in a mouse model of IBD. Lacking any central effect, cannabidiol is an attractive option for treating inflammatory diseases.

Aim

To assess the effects of cannabidiol on Crohn’s disease in a randomized placebo-controlled trial.

Patients and Methods

Twenty patients aged 18–75 years with a Crohn’s disease activity index (CDAI) >200 were randomized to receive oral (10 mg) CBD or placebo twice daily. Patients did not respond to standard treatment with steroids (11 patients), thiopurines (14), or TNF antagonists (11). Disease activity and laboratory parameters were assessed during 8 weeks of treatment and 2 weeks thereafter. Other medical treatment remained unchanged.

Results

Of 20 patients recruited 19 completed the study. Their mean age was 39 ± 15, and 11 were males. The average CDAI before cannabidiol consumption was 337 ± 108 and 308 ± 96 (p = NS) in the CBD and placebo groups, respectively. After 8 weeks of treatment, the index was 220 ± 122 and 216 ± 121 in the CBD and placebo groups, respectively (p = NS). Hemoglobin, albumin, and kidney and liver function tests remained unchanged. No side effects were observed.

Conclusion

In this study of moderately active Crohn’s disease, CBD was safe but had no beneficial effects. This could be due to lack of effect of CBD on Crohn’s disease, but could also be due to the small dose of CBD, the small number of patients in the study, or the lack of the necessary synergism with other cannabinoids. Further investigation is warranted.

ClinicalTrials.gov

NCT01037322.

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References

  1. Pariente B, Laharie D. Review article: why, when and how to de-escalate therapy in inflammatory bowel diseases. Aliment Pharmacol Ther. 2014;40:338–353. doi:10.1111/apt.12838.

    Article  CAS  PubMed  Google Scholar 

  2. Massa F, Storr M, Lutz B. The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. J Mol Med (Berl). 2005;83:944–954.

    Article  CAS  Google Scholar 

  3. Izzo AA, Camilleri M. Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects. Gut. 2008;57:1140–1155.

    Article  CAS  PubMed  Google Scholar 

  4. Lal S, Prasad N, Ryan M, et al. Cannabis use amongst patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2011;23:891–896.

    Article  PubMed  Google Scholar 

  5. Naftali T, Lev LB, Yablecovitch D, Half E, Konikoff FM. Treatment of Crohn’s disease with cannabis: an observational study. [Erratum appears in Isr Med Assoc J. 2011;13:582 Note: Yablekovitz, Doron (corrected to Yablecovitch, Doron)]. Isr Med Assoc J IMAJ. 2011;13:455–458.

  6. Weiss A, Friedenberg F. Patterns of cannabis use in patients with inflammatory bowel disease: a population based analysis. Drug Alcohol Depend. 2015;156:84–89.

    Article  PubMed  Google Scholar 

  7. Moore THM, Zammit S, Lingford-hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370:319–328.

    Article  PubMed  Google Scholar 

  8. Zhang MW, Ho RCM. The cannabis dilemma: a review of its associated risks and clinical efficacy. J Addict. 2015;2015:1–6.

    Article  Google Scholar 

  9. Gaoni Y, Mechoulam R. The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish. J Am Chem Soc. 1971;93:217–224.

    Article  CAS  PubMed  Google Scholar 

  10. Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus LO. Cannabidiol—recent advances. Chem Biodivers. 2007;4:1678–1692.

    Article  CAS  PubMed  Google Scholar 

  11. Zuardi AW. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action Canabidiol: de um canabinóide inativo a uma droga com amplo espectro de ação. Rev Bras Psiquiar. 2008;30:271–280.

    Article  Google Scholar 

  12. Esposito G, De Filippis D, Cirillo C, et al. Cannabidiol in inflammatory bowel diseases: a brief overview. Phyther Res. 2012;2013:633–636.

    Google Scholar 

  13. Burstein S. Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorg Med Chem. 2015;23:1377–1385.

    Article  CAS  PubMed  Google Scholar 

  14. Sacerdote P, Martucci C, Vaccani A, et al. The nonpsychoactive component of marijuana cannabidiol modulates chemotaxis and IL-10 and IL-12 production of murine macrophages both in vivo and in vitro. J Neuroimmunol. 2005;159:97–105.

    Article  CAS  PubMed  Google Scholar 

  15. Kozela E, Pietr M, Juknat A, Rimmerman N, Levy R, Vogel Z. Cannabinoids delta(9)-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-kappaB and interferon-beta/STAT proinflammatory pathways in BV-2 microglial cells. J Biol Chem. 2010;285:1616–1626.

    Article  CAS  PubMed  Google Scholar 

  16. Capasso R, Borrelli F, Aviello G, et al. Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice. Br J Pharmacol. 2008;154:1001–1008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schicho R, Storr M. Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology. 2012;89:149–155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153:199–215.

    Article  CAS  PubMed  Google Scholar 

  19. Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci. 2009;30:515–527.

    Article  CAS  PubMed  Google Scholar 

  20. De Filippis D, Esposito G, Cirillo C, et al. Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PLoS ONE. 2011;6:e28159.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Katsidoni V, Kastellakis A, Panagis G. Biphasic effects of Δ9-tetrahydrocannabinol on brain stimulation reward and motor activity. Int J Neuropsychopharmacol. 2013;16:2273–2284.

    Article  CAS  PubMed  Google Scholar 

  22. Fasinu PS, Phillips S, Elsohly MA, Walker LA. Current status and prospects for cannabidiol preparations as new therapeutic agents. Pharmacotherapy. 2016;36:781–796.

    Article  PubMed  Google Scholar 

  23. Wright MJ, Vandewater SA, Taffe MA. Cannabidiol attenuates deficits of visuospatial associative memory induced by delta9tetrahydrocannabinol. Br J Pharmacol. 2013;170:1365–1373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kwiatkowska M, Parker LA, Burton P, Mechoulam R. A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew). Psychopharmacology. 2004;174:254–259.

    Article  CAS  PubMed  Google Scholar 

  25. Hawksworth G, McArdle K. Metabolism and pharmacokinetics of cannabinoids. In: Guy GC, Robson PJ, Whittle BA, eds. The Medicinal Uses of Cannabis and Cannabinoids. London: London Pharmaceutical Press; 2004:205–228.

    Google Scholar 

  26. Kang M, Ragan BG, Park J-H. Issues in outcomes research: an overview of randomization techniques for clinical trials. J Athl Train. 2008;43:215–221.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid–terpenoid entourage effects. Br J Pharmacol. 2011;163:1344–1364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Leo A, Russo E, Elia M. Cannabidiol and epilepsy: rationale and therapeutic potential. Pharmacol Res. 2016;107:85–92.

    Article  CAS  PubMed  Google Scholar 

  29. Kumar RN, Chambers WA, Pertwee RG. Pharmacological actions and therapeutic uses of cannabis and cannabinoids. Anaesthesia. 2008;56:1059–1068.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology, Meir Medical Center, 59 Tchernihovsky st., 4441002, Kfar Saba, Israel

    Timna Naftali, Gila Gabay, Asaf Stein, Miriam Bronshtain, Ido Laish, Fabiana Benjaminov & Fred M. Konikoff

  2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Timna Naftali, Gila Gabay, Asaf Stein, Miriam Bronshtain, Ido Laish, Fabiana Benjaminov & Fred M. Konikoff

  3. School of Pharmacology, Hadassa Medical School, Hebrew University of Jerusalem, Jerusalem, Israel

    Refael Mechulam

  4. Faculty of Pharmacology, School of Medicine, Hebrew University, POB 1221, 9112102, Ein Karem, Jerusalem, Israel

    Refael Mechulam

  5. Hilel Yafe Medical Center, Hshalom st., 38100, Hadera, Israel

    Amir Marii

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  1. Timna Naftali
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  2. Refael Mechulam
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Correspondence to Timna Naftali.

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Naftali, T., Mechulam, R., Marii, A. et al. Low-Dose Cannabidiol Is Safe but Not Effective in the Treatment for Crohn’s Disease, a Randomized Controlled Trial. Dig Dis Sci 62, 1615–1620 (2017). https://doi.org/10.1007/s10620-017-4540-z

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