Table 1. Systematic Review Summary .

IBD: Inflammatory Bowel Disease; UC: Ulcerative Colitis; CD: Crohn's Disease; GPR: G-protein coupled receptor; CD: Cluster of Differentiation; THC: Tetrahydrocannabinol; ROS: Reactive Oxygen Species; CBG: Cannabigerol; FO: Fish Oil; CAuNP: Core Gold Nanoparticles; CAgNP: Core Silver Nanoparticles; NLC: Nanostructured Lipid Carrier 

Author(s)	Year	Results	Research Implications
Pellino et al.	(2020) [1]	Cannabinoids were observed to be effective and safe in mitigating symptom severity in patients with IBD.	The study recommended the need for future studies to focus on varying levels of dosage and the impact on patient recovery from IBD disease.
Mak et al.	(2020) [2]	The addition of statin/aspirin did not yield additional benefits concerning chemoprevention.	In Chinese IBD patients, the clinical benefit of statin/aspirin addition during chemoprevention is yet to be established.
Li et al.	(2019) [3]	The Pathway Activation for the Single Sample technique was found to be reliable in predicting IBD precisely.	In the future, significant features in cannabinoids that could inform their efficacy for use with IBD patients are an area worth investigating.
Hansen et al.	(2019) [4]	The use of cannabis for self-medication in IBD persons was found to exhibit increased vulnerability to substance abuse.	Before using cannabis for IBD symptom treatment, screening for vulnerability to substance misuse and mental health comorbidities is key.
Papamichael et al.	(2020) [5]	Immunomodulator addition was found to increase drug concentrations and attenuate immunogenicity, hence anti-TNF agents’ pharmacokinetic profile improvement in IBD patients.	Combination therapy during cannabinoid use with IBD patients is an area worth considering in clinical environments.
Kafil et al.	(2019) [6]	In adults with UC and CD, no firm conclusions arose relative to cannabinoid and cannabis effectiveness and safety.	There is a need for further examination to ascertain the efficacy of the selected compounds.
Downer	(2020) [7]	Terpenes were found to exhibit anti-inflammatory properties.	Terpenes could be considered for use in ongoing cannabinoid-based therapies in IBD patients.
Weinberger et al.	(2020) [8]	Cannabis was found to exacerbate IBD, compounded by its increasing use in patients with depression.	Early screening for comorbidities is key when considering the use of cannabinoids and cannabis in IBD patients.
Andersen et al.	(2020) [9]	Cannabis use was avowed to predict levels of GPR15+CD3+CD4+ helper T cells	The efficacy of cannabinoids in terms of safety and effectiveness was documented, but larger samples ought to be considered in the future to ascertain the results.
Kienzl et al.	(2020) [10]	Cannabis was found to steer improvements in health-related quality of life for IBD patients, but the ability to reduce inflammatory markers remained a dilemma.	Given that heavy opioid use may come with higher mortality and opioid dependency, future clinical trials ought to focus on the magnitude of the dosage and ascertain levels that come with optimal patient outcomes.
Becker et al.	2020 [11]	The results of this investigation demonstrated the efficacy of delta-9-tetrahydrocannabinol in attenuating anti-CD40-induced colitis and colitis-associated colon cancer.	In the future, the study’s insights can form a foundation for the eventual examination of tissues from different sites to determine delta-9-tetrahydrocannabinol effects, including in the colon’s mucosal barrier sites.
Wang et al.	2022 [12]	In the findings, it was reported that zein-WP nanoparticles are superior in cannabinoid protection against UV.	The implication for future clinical practice is that the findings could inform the process of zein-WP nanoparticle encapsulation, hence improvements in cannabinoid release in vitro and also its antioxidant activity.
Borrelli et al.	(2013) [13]	Cannabigerol was found to attenuate murine colitis, as well as reduce the formation of reactive oxygen species in intestinal epithelial cells.	In IBD patients, Cannabigerol could be considered for clinical use or application.
Irving et al.	2018 [14]	The aim was to investigate the effect of botanical extracts rich in cannabinoids on IBD symptom severity. The results demonstrated that in individuals who tolerate the extracts, therapeutic benefits are felt. However, multiple limitations characterized the interpretation, including the failure to give insight into the implications for persons with drug intolerance.	The results could be used in the future to discern the impact of botanical extracts rich in cannabinoids on IBD symptoms in severe cases.
Naftali et al.	(2013) [15]	Significant clinical and steroid-free benefits were noted following the use of THC-rich cannabis for a short course of eight weeks.	In the future, studies with larger patient groups could be used to ascertain these findings.
Naftali et al.	2021 [16]	This study sought to investigate the impact of THC-rich cannabis usage on a short-term treatment basis. In UC patients, the results demonstrated beneficial clinical effects.	Future clinical practices could build on these results to seek to give insight into the degree of anti-inflammatory improvement and any moderating role brought about by potential laboratory markers.
Naftali et al.	2017 [17]	The safety of cannabinoids in moderately active Crohn’s disease patients was documented.	The study recommended the need for future studies to focus on a larger number of patients and also assess the moderating effect of the dosage level.
Nallathambi et al.	2017 [18]	When administered in low concentration, cannabinoid poses anti-inflammatory activity. However, the side effect is that it comes with dose-dependent cytotoxic activity, especially in high concentrations.	The results could be used to guide the treatment of colon tissues in IBD patients.
Cocetta et al.	2021 [19]	Cannabinoid as a compound was observed to yield promising results in relation to the treatment of intestinal inflammatory status via ROS production inhibition.	These findings are crucial for guiding the restoration of the permeability of the epithelium
Couch et al.	2019 [20]	With palmitoylethanolamide and cannabidiol implementation, human colon permeability is reduced.	The implication of the results can be felt in disorders involving gut permeability increase, with IBD unexceptional
Pagano et al.	2021 [21]	When CBG’s per se inactive dose, cannabinoid, and FO were combined, promising effects entailing intestinal anti-inflammation were reported.	The findings inform how, in the colon and in the serum, phytocannabinoid levels could be altered and yield positive patient outcomes.
Silvestri et al.	2020 [22]	With the co-administration of cannabinoids in low concentration and fish oil, the compounds were found to yield reductions in colon inflammation.	In the future, the findings can be used to determine the mechanism of action that explains Akkermansia muciniphila elevation.
Singh et al.	2012 [23]	Cannabis sativa extracts were investigated to determine how they could be used for economical and rapid nanoparticle green synthesis, with findings depicting the extracts’ effectiveness in curbing the formation of biofilms.	The results could be used in the future to guide how to prevent CAgNPs, C-AuNPs, and F-AuNPs, from forming.
Pagano et al.	2019 [24]	The authors strived to assess the effect of cannabinoid compounds on cytokine expression in pediatric groups with colonic biopsies due to UC. The results saw cannabinoids exert intestinal anti-inflammatory effects in the study subjects.	In future clinical environments, the results might be useful in prompting the examination of the extent to which cannabinoids might reduce cytokine expression in the rest of the population, eventually supporting clinical decision-making.
Hoffenberg et al.	2018 [25]	The motivation of the investigation involved understanding the effect of marijuana on IBD suppression in young adults and adolescents, with findings suggesting that whereas the product is perceived to be beneficial, testing and screening are key to mitigating adverse events.	Indeed, the results could help in the future to develop guidelines for informing the needed formulations for addressing IBD in young adults and adolescents.
Matarazzo et al.	2021 [26]	This study sought to uncover the role of in-situ gelling hydrogels in driving cannabinoids as drugs that are highly lipophilic. The results suggested that the hydrogels are not suitable, but promising formulations exist in the form of CBD-NLC dispersions, especially through CBD’s nasal administration.	The results could be used in the future to inform optimal formulations through which better cannabinoid compound-based interventions might help to address IBD in patients.
Harvey et al.	2014 [27]	The correlation between cannabinoid ligands and the mitigation of mucosal damage was the central purpose of the study, with the efficacy of cannabinoids documented.	The study’s inferences could aid in the future in determining cannabinoid compound formulations that could aid in restoring human colon functioning.
Tartakover Matalon et al.	2021 [28]	The impact of cannabis on the eCB tone was investigated. In UC patients, the beneficial effects of the compound were documented, including symptom relief.	The study was essential by paving the way for the future understanding of how cannabis may affect the quality of life in patients with different demographic features from both the clinical implications and anti-inflammatory impact perspectives.
Nso et al.	2021 [29]	In patients with IBD, cannabinoids were found to yield promising outcomes such as reduced clinical complications and better general well-being.	The study pointed to the need for future investigations to be conducted in terms of randomized controlled trials to gain further insight.