An overview of global monitoring systems for the side effects and adverse events associated with medicinal cannabis use: A scoping review using a systematic approach

The use of cannabis-based medicines (CBM) as a therapeutic has grown exponentially over the last 5 years in Australia. Prior to this increase, there was significant legislative resistance to the use of CBM for clinical trials, hence pre-clinical data is limited. Safety monitoring systems for CBM are not structured and do not fit easily into the workflow of busy health professionals. Hence, post-marketing surveillance of CBM is patchy. CBM are available in many countries globally and face similar issues in relation to pharmacovigilance. The objective of this review is to answer the following question: What are the systems in place internationally to monitor side effects and adverse events of cannabis use as a medicine? We used the PICO framework to develop keyword elements, which guided two search queries. Each query contained a different combination of keywords to increase sensitivity and specificity of the search. Both queries were entered into Embase and Scopus for retrieval of quality relevant peer-reviewed literature. Only the second search query, was used for the grey literature. Fifty-four full text articles were included in the review, thirty-nine were from the peer-reviewed search, eight were from the grey literature search, and seven were from citations of relevant texts. Our search yielded two main forms of monitoring systems: databases and registries, with databases often created by regulatory authorities. There was great variability within these systems, differing in methods of causality assessment, level of detail collected, terminology, and affiliations. Only one monitoring system captured in our search obligated reporting from patients. VigiBase remains the largest form of centralised monitoring, receiving case reports internationally. Regardless of the scope of VigiBase, there remains heterogeneity of data within the system. As such, our study reaffirms a greater need for a centralised, consistent, and accessible system for the post-marketing surveillance of side effects and adverse events associated with usage of CBM. What is already known on this topic What this review adds How this study might affect research, practice, or policy (summarise implications) ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement National Health and Medical Research Council (NHMRC) through the Centre of Research Excellence scheme (NHMRC CRE APP1135054) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript * CBM : Cannabis-based medicines TGA : Therapeutic Goods’ Administration CBD : Cannabidiol THC : Delta-9-tetrahydrocannabinol MS : Multiple sclerosis RA : Rheumatoid arthritis Irritable Bowel syndrome: IBS FAERS : FDA Adverse events reporting system CVAR : Canada Vigilance Adverse Reaction Online Database EDSADR : Eudravigilance European Database of Suspected Adverse Drug Reaction Reports DAEN : TGA Database of Adverse event Notifications UKMCR : UK Medical Cannabis Registry AIFA : Italian Medicines Agency