Implementation of the presented labeling scoring system could help guide professional prescribers and patients on which products sold in Brazil have the necessary information for safe prescription and use, given the wide range of products available and the regulations in force. Based on 45 items, the 105 selected products were evaluated and scored according to the weights assigned to them, which reflect the importance of this criterion for the proper prescription and use of the CBD-based products. Most of the evaluated products were rated as satisfactory (47), followed by 39 classified as not very satisfactory and 19 as very satisfactory. The lack of publicly available product information was the reason for most of the products falling into the two lower categories (satisfactory and not very satisfactory). The scores for the labeling quality criteria reflect the difficulties that prescribers and patients in Brazil face when prescribing/using CBD-based products, especially those from the N660. A yearbook mapping the cannabis market in Brazil estimated that in 2023, there were approximately 219,000 patients in the country who imported cannabis-based products, 114,000 who purchased through cultivation and distribution associations, and 97,000 who benefited from direct purchases from pharmacies/drugstores (Kaya-Mind 2023).

This study showed a wide variation in the labeling quality criteria of CBD-based products marketed in Brazil, both in the N327 and N660 groups, in the four domains evaluated. In the direct comparison between these two classes of products, there was a general difference between them. The N327 group had a significantly higher median score than the N660 group. Therefore, it can be concluded that products that have been notified with a temporary trade permit by the regulatory agency present quality information in a more accessible way than imported products, as it is a requirement that the package leaflet and standard packaging be made available on the official ANVISA website for products that have a trade permit.

In the prescription and safety of use domains, there was a significant difference in the final scores between the two product classes, i.e., the products in the N327 group performed better than those in the N660 group. No difference was found between the two classes of products in the areas of GMP and laboratory tests. This result was to be expected since, during the data collection, it was observed that neither the companies responsible for the imported products nor the companies with temporary trade permits in the country generally provide the data related to these two domains.

A significant difference was observed in the prescription domain when comparing products in the N327 group to those in the N660 group. The main factor contributing to this result was the requirement by the regulatory authority for package leaflets for those receiving temporary marketing authorizations, since most of the information about the product is found on the package leaflet, such as the correspondence between drops/mL, which is essential for prescribing. During the evaluation, it was observed that the products with the lowest scores for items related to the prescription requirements established by ANVISA were those in the N660 group. The Brazilian regulations (ANVISA, 2019) aim to establish the country's requirements for prescribing cannabis-based products. However, there are differences between N660 and N327. Ideally, relevant information should be provided to the patient at the time of prescription, including health risks, proof of safety and efficacy, possible adverse events, and precautions for use. Nonetheless, there are gaps in this information. There is still a significant difference between the two classes of products. The N327 products provide more information to consumers, although they do not present safety and efficacy data. Some authors highlight the importance of prescribing cannabis correctly, showing that communication, transparency about the treatment to the patient, and correct dispensing with proper guidance are essential information (Arnold et al. 2020; MacDonald & Adams., 2019). Thus, prescribing becomes easier and safer with more information available about the product. Prescribing a correctly titrated formulation with a known amount of active ingredients allows for more consistent therapeutic management and a better risk–benefit ratio (Citti et al. 2016; Romano & Hazekamp 2013; SIFAP, 2016).

In contemporary clinical practice, some providers consider using cannabis for conditions that are resistant to conventional treatment (i.e., epilepsy that is resistant to reference drugs). In contrast, others choose not to include cannabis in their therapeutic list due to the lack of robust evidence (Graham et al., 2023). Other providers are unaware of the therapeutic properties of cannabinoids, and there are still professionals who incorporate these products as adjuncts to integrative and complementary therapy. Thus, one of the most important aspects to be analyzed is the patient's responsiveness. For the best response, prescribers can adapt the treatment to their needs by changing the concentrations of the active ingredients, such as THC and CBD, of the products or their routes of administration (Beckett Wilson & Metcalf McGrath 2023). If the manufacturer refrains from providing information on the phytocannabinoids and terpenes present in the formulation, it is not possible to change this dose titration or product.

Safety of use was the area that showed the most significant difference between the N327 and N660 products. In other words, the products which received marketing authorization from the regulatory agency, even if temporary, had better scores on the items relating to the safety of use than those only authorized for import. Once again, the main factor contributing to this significant difference between the products is ANVISA's requirement for package leaflets for those which have received temporary marketing authorization. This is because most of the quality criteria relating to the safety of use domain are also found in the package leaflet, and those products without registration/temporary trade authorization are not required to present it.

The number of "CBD-containing" products available for sale, especially online, has grown exponentially in the USA. In addition, there is a lack of quality oversight and federal regulation of these products, which has led to an uncontrolled CBD market that, in turn, can result in negative outcomes, both concerning use and patient safety (Koturbash et al., 2020). A study conducted in the state of Mississippi (USA) of 25 commercially available CBD and THC-based products identified a marked variability between the actual CBD content and the declared amounts; only three were within ± 20% of their label declaration. In addition, the THC content of three products exceeded the legal limit of 0.3%, and four products were adulterated with synthetic cannabinoids, e.g., semi-synthetic ∆8-THC or HHC. The results of this study clearly demonstrated that most product labels did not accurately reflect the actual content and composition of the cannabinoids present and were, therefore, considered fraudulent, posing risks to the safety of use. The authors advocate the development of current GMP and their strict enforcement for cannabinoid products (Gurley et al. 2020). A South African study found that only three of the 40 products analyzed contained CBD at levels with a 90–110% margin of error. In addition, some of these products, which were supposed to be water-soluble, did not show a good aqueous solubility profile, and two products contained traces of THC (Mouton et al. 2024). This patchwork of laws and regulations surrounding the market for cannabis-based products in various countries around the world, as well as in the different states in the United States that authorize their use, has been widely discussed and pointed out by the scientific community as a risk to the safe use of these products (Britch et al., 2021; Pruyn et al. 2022).

There was no difference between the products from N327 for the GMP domain and those from N660. Most imported products come from the USA, where there is no federal oversight, and standards vary considerably between states. The FDA has approved the use of a few cannabis-based prescription products (Koturbash & MacKay 2020); otherwise, the FDA does not currently regulate CBD products as CBD is not considered a dietary supplement or food additive. However, it does issue safety announcements to warn the public of the potential risks of intoxication and that it is not just any product "good for everything" (Wagoner et al., 2021; Walker et al. 2020). The Brazilian regulatory agency considers cannabis-based products as medication, but even for N327 products, manufacturers have no legal obligation to provide data from laboratory tests involving user safety. As such, there was no difference between the groups, as much data was not provided.

Similarly, there was no difference between the two classes of products regarding the provision of laboratory tests. Even though some products did provide a laboratory test (31% of the N327 group and 45% of the N660 had a CoA), the majority did not. This may be directly linked to the fact that ANVISA does not require the information contained in the CoA to be made public, thereby leaving it up to the company to determine whether or not to make it available. The lack of transparency makes it challenging to obtain the desired information. It was also noted that, during the evaluation of the products in the N660 group, many manufacturers who made the CoA available had not carried out all the tests that were considered in this study (phytocannabinoid concentration, terpene characterization, presence of residues, contamination, microbiology, toxins, inorganic metals and foreign bodies, etc.), which may have influenced the scores of these products. Labeling claims (ingredients and their concentrations) are untrustworthy without a CoA. However, even if a product contains a CoA, it cannot always be trusted. Studies have demonstrated fraudulent labeling practices in the cannabis marketplace, including incomplete/incorrect label claims and false/incorrect CoA (Gurley et al. 2020; Mouton et al. 2024). Laboratory tests are extremely important for monitoring and controlling the quality of medications since phytocannabinoids can produce diverse effects and interfere with therapeutic management (Fischedick et al., 2010b). It is, therefore, imperative to implement control methods to guarantee the uniformity and quality of formulations (Omar et al., 2013) in order to provide users with a reliable product and ensure that providers are prescribing an accurate treatment. (Dussy et al. 2005; Fischedick et al. 2010a; Fischedick et al. 2010b).

The utilization of cannabis-based products is constrained not only in Brazil but also on a global scale. A paucity of controlled studies with an adequate sample size to yield clinically significant conclusions for diseases where potential benefits have been observed hampers the development of robust scientific evidence to support therapeutic indications. The masking of the placebo group, particularly in the case of products containing THC, represents a significant challenge for research centers engaged in the conduct of such studies. Furthermore, the quality control of currently available products is constrained by the absence of standardized testing protocols and methodologies designed to ensure the safety of users and prescribers. This is particularly evident in the absence of guidelines comparable to the pharmaceutical GMP. Brazil has established regulatory guidelines for GMPs for pharmaceuticals, including RDC 17/10 (Ministry of Health 2010), which has become the principal regulatory framework on this subject in the country, and RDC 658/22 (Ministry of Health 2022a, b), which presents the general guidelines for GMPs for pharmaceuticals.

Additionally, specific regulations have been established for cannabis-based products (Ministry of Health 2019). Subsequently, following a period of five years during which the regulation was in force, an extensive review was conducted. A report published by ANVISA indicated that the text of the regulation will be updated as soon as consultations and public hearings have been conducted to facilitate the implementation of the proposed changes. Introducing the revised regulatory framework is anticipated to result in a notable increase in the number of registered products within the country (ANVISA, 2023).

The regulation of cannabis for its health applications must be transparent, accountable, and publicly involved. These principles ensure that cannabis is used optimally, enhancing its therapeutic effects and mitigating adverse events (Gumilang et al. 2024). The more rigorous labeling quality criteria are established for these products, the greater the benefit to users. (Gurley et al. 2020; Johnson et al. 2022).