Cannabinoid Therapeutic Effects in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Abstract
:1. Introduction
1.1. Background
1.2. Study Rationale and Hypothesis
1.3. Objectives
2. Methods
2.1. Stakeholder Involvement (PPI)
2.2. Eligibility Criteria
- Study design:
- ○
- Randomized Controlled Trial (RCT);
- ○
- Prospective case-control study;
- Exposure:
- ○
- Treatment with cannabinoids, by either inhalation or oral administration.
- Outcome:
- ○
- Clinical evaluation of the patient, either via standard-use scale or via other validated clinical measurement.
- Publication type:
- ○
- Primary studies published in peer-reviewed journals;
- ○
- Non-peer reviewed publications and grey literature articles (e.g., trial results), as long as they are publicly available.
- Study design:
- ○
- Cross-sectional (prevalence) studies;
- ○
- Case reports and case series;
- ○
- Prospective and retrospective studies without measures of association and confidence intervals (or data enabling to calculate them);
- ○
- Studies with no comparison.
- Publication type:
- ○
- Abstracts with no data available (i.e., conference abstracts, unless providing data for analysis);
- ○
- Studies reporting results that have been superseded by subsequent reports from the same study (note: this includes conditions when that reports include a mix of results that have or have not been updated).
2.3. Information Sources and Search Strategies
2.4. Addressing Bias
- It was chosen to include only prospective controlled studies (both RCT and NRS) in the selection process, since they provide the least biased results while still permitting reasonable statistical precision;
- Risk of Bias was rated using a specific, validated tool in our protocol;
- Sensitivity analyses were performed by executing a leave-one-out analysis, consisting in performing multiple meta-analyses by excluding one study at each step, and a meta-regression [31].
2.5. Selection Process
2.6. Data Collection Process
2.7. Data Items
- Publication year;
- Involved country;
- Disease type;
- Treatment type and duration;
- Control type;
- Follow-up time;
- Study effect measure;
- Number of patients in each cohort;
- Therapeutic successes in each cohort;
- Therapeutic failures in each cohort.
- When available, variation in disease activity index in each cohort was also retrieved.
2.8. Study Risk of Bias Assessment
2.9. Effect Measures
2.10. Synthesis Methods
2.11. Reporting Bias Assessment
2.12. Certainty Assessment
2.13. Reporting
3. Results
3.1. Study Selection
3.2. Study Characteristics
3.3. Risk of Bias in Studies
3.4. Results of Individual Studies
- Effectiveness of cannabinoid supplementation on clinical outcome
- Effectiveness of cannabinoid supplementation on disease activity reduction, quality of life and other variables
3.5. Results of Synthesis
3.6. Risk of Reporting Bias in Syntheses
3.7. Certainty of Evidence
4. Discussion
4.1. Results in Context
4.2. Limitations of Included Studies
4.3. Limitations of the Review Methods
4.4. Implications
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Registration and Protocol
References
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Population | Patients with IBD |
Intervention | Cannabinoid administration |
Comparison | Standard treatment |
Outcome | Improvement in patient’s clinical condition |
Database | Search String(s) | Filters |
---|---|---|
MEDLINE | ((ulcerative colitis) OR (crohn) OR (inflammatory bowel disease) OR colitis) and (Cannabis or cannabinoids or THC or cannabidiol) | Publication year: >2000 |
Scopus | ((ulcerative AND colitis) OR (crohn) OR (inflammatory AND bowel AND disease) OR colitis) AND (cannabis OR cannabinoids OR thc OR cannabidiol) PUBYEAR > 2002 AND PUBYEAR > 2001 AND (LIMIT-TO (DOCTYPE, “ar”)) AND (LIMIT-TO (EXACTKEYWORD, “Controlled Study”) OR EXCLUDE (EXACTKEYWORD, “Animals”) OR EXCLUDE (EXACTKEYWORD, “Animal Experiment”)) | Not Applicable (already included in string search) |
ClinicalTrials.gov (accessed on 10 August 2022) | Disease Type: Inflammatory Bowel Disease (automatic field) Additional keywords: Cannabis | Not Applicable |
Authors | Year of Publication | Country | Included Population | Intervention | Control | Effect Measure | Treatment Duration | Follow-Up |
---|---|---|---|---|---|---|---|---|
Naftali et al. [43] | 2013 | Israel | 21 CD | Cigarette smoking: 0.5 g of dried cannabis flowers, equivalent to 11.5 mg of THC twice daily. | Cigarette smoking w/o cannabis after THC extraction. | CDAI | 8 weeks | 2 weeks |
Naftali et al. [44] | 2017 | Israel | 19 CD | Cannabinoid oil at a concentration of 5 mg/mL (0.3 mg/kg). | Placebo containing pure olive oil | CDAI | 8 weeks | 2 weeks |
Matalon et al. [45] | 2021 | Israel | 30 CD 19 UC | Cigarette smoking: 0.5 g of dried cannabis flowers, equivalent to 11.5 mg of THC. | Cigarette smoking w/o cannabis after THC extraction. | Endocannabinoid blood level change; CDAI; BM; QOL; immunohistochemistry measures. | 8 weeks | None |
Naftali et al. (UEG) [46] | 2018 | Israel | 46 CD | Cannabis oil 15% cannabidiol + 4% tetrahydrocannabinol | Placebo | Clinical Remission | 8 weeks | None |
Irving et al. [47] | 2018 | United Kingdom | 60 UC | Cannabidiol-rich botanical extract capsules, up to 500 mg/day | Placebo capsules | Mayo score; IBDQ score; PGAS score; stool frequency NRS; rectal bleeding NRS pain 0–10 NRS score. | 10 weeks | 1 week baseline + 1 week follow-up |
Naftali et al. [48] | 2021 | Israel | 32 UC | Cigarette smoking: linear increasing up to 1 g/day of dried cannabis flowers (0.25 g steps), equivalent to 23 mg of THC. | Cigarette smoking w/o cannabis after THC extraction. | Lichtiger index; QOL; Mayo endoscopic score | 8 weeks | 2 weeks |
Study ID | Domain 1 | Domain 2 | Domain 3 | Domain 4 | Domain 5 | Overall |
---|---|---|---|---|---|---|
Irving 2018 | Low Risk | Low Risk | Low Risk | Low Risk | Low Risk | Low Risk |
Matalon 2021 | Low Risk | Some Concerns | High Risk | Low Risk | Low Risk | High Risk |
Naftali 2013 | Low Risk | Some Concerns | Low Risk | Low Risk | Low Risk | Some Concerns |
Naftali 2017 | Low Risk | Some Concerns | Low Risk | Low Risk | Some Concerns | Some Concerns |
Naftali 2018 | Some Concerns | Some Concerns | Low Risk | Some Concerns | Some Concerns | Some Concerns |
Naftali 2021 | Low Risk | Low Risk | Low Risk | Low Risk | Low Risk | Low Risk |
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Vinci, A.; Ingravalle, F.; Bardhi, D.; Cesaro, N.; Frassino, S.; Licata, F.; Valvano, M. Cannabinoid Therapeutic Effects in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Biomedicines 2022, 10, 2439. https://doi.org/10.3390/biomedicines10102439
Vinci A, Ingravalle F, Bardhi D, Cesaro N, Frassino S, Licata F, Valvano M. Cannabinoid Therapeutic Effects in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Biomedicines. 2022; 10(10):2439. https://doi.org/10.3390/biomedicines10102439
Chicago/Turabian StyleVinci, Antonio, Fabio Ingravalle, Dorian Bardhi, Nicola Cesaro, Sara Frassino, Francesca Licata, and Marco Valvano. 2022. "Cannabinoid Therapeutic Effects in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials" Biomedicines 10, no. 10: 2439. https://doi.org/10.3390/biomedicines10102439
APA StyleVinci, A., Ingravalle, F., Bardhi, D., Cesaro, N., Frassino, S., Licata, F., & Valvano, M. (2022). Cannabinoid Therapeutic Effects in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Biomedicines, 10(10), 2439. https://doi.org/10.3390/biomedicines10102439