The regulation and the wide range of studies among medical cannabis has been changing its role among the therapeutic tools available for practitioners worldwide. Medical cannabis changed over the years from plant-based or extract-based uses, to isolated compounds of plant or synthetic origin in a broad spectrum of vehicles, administration routes, doses and purity (Wyse and Luria, 2021). However, the types, numbers and qualities of the studies have also been dispersed among new medical interventions and health outcomes.

From a pharmacological standpoint, the therapeutic potential of cannabis relies on its main active compounds, namely phytocannabinoids (such as THC and CBD), and partially on other phytochemicals like terpenes and flavonoids (Desaulniers et al., 2021). Although these active compounds elicit biological responses by several mechanisms of action, their ability to interact with cannabinoid receptors and modulate the activity of the endocannabinoid system is at the core of their pharmacological potential (Lu and Mackie, 2021).

It is crucial to conduct thorough studies on medical cannabis, especially with recent investigations such as the University of Colorado’s focus on high-concentration cannabis (Bero et al., 2021) and Groening et al. (2024) evidence mapping on cannabis use and psychosis. The wide variety of product types, conditions treated, and outcomes makes it difficult to draw clear conclusions (Pratt et al., 2019). As data on cannabis use is often mixed, there is an urgent need for high-quality, unbiased, and well-organized evidence. Unfortunately, many studies lack the necessary rigor and objectivity, hindering informed decision-making. Therefore, providing reliable data is essential to support clinical practice and policy development. Hence, the objective of this article is to map the effectiveness of medical cannabis regarding health outcomes.

The methodology involved in building an evidence map is similar to that of a systematic review. However, while a systematic review attempts to answer a specific question using a subset of primary clinical studies, an evidence map represents a level above as it is based on systematic reviews generating a broader overview, broadening the horizon of objectives, and has been more widely used to inform public policy.

The Campbell Collaboration suggests that any evidence map is an attempt to create a systematic presentation aiming at organizing information, identifying gaps, facilitating decision-making and visualizing relationships. The map is usually accompanied by a report summarizing the evidence for stakeholders such as researchers, research commissioners, policymakers, and practitioners (Shlonsky et al., 2011).

This Evidence Map summarizes clinical evidence on the use of medical cannabis, including the health conditions, interventions and clinical outcomes. For this evidence map creation, the following six steps were considered (Wyse and Luria, 2021): Definition of the map scope (Desaulniers et al., 2021), Establishment of the working group (Lu and Mackie, 2021), Systematic search and study selection (Bero et al., 2021), Characterization of the evidence (Groening et al., 2024), Generation of the interactive evidence map, and (Pratt et al., 2019) Preparation of the map synthesis. Each step had its own activities involved (Schveitzer et al., 2021). The study was conducted following the International Initiative for Impact Evaluation (3iE) Evidence Gap Methodology, and results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Page et al., 2021). The Evidence Maps were supported by a technical expert panel of librarians, practitioners, policymakers, and research experts as collaboration between the Latin American and Caribbean Center on Health Sciences Information, also known as BIREME, is a specialized Unit of the Pan American Health Organization/World Health Organization (PAHO/WHO) and the Brazilian Academic Consortium for Integrative Health (CABSIN).

From a total of 1840 references, 279 potential studies were selected and read in full, and 194 studies were included in the map. This process is displayed at the PRISMA Flow Diagram (Figure 1).

References could be found from any year, but references that met the inclusion criteria were only found from July 2001 to April 2023. The reasons for excluding studies were: reviews that already have a more recent version (in this case, we only included the most recent version of each review), types of studies that did not meet the inclusion criteria (event summaries, overviews or clinical trials) or studies that evaluated other interventions (did not examine medical cannabis).

The complete list of references of the 194 systematic reviews included in the map is provided in Supplementary Material. The majority of systematic reviews were published from 2018 onwards and more than half of the studies included in the systematic reviews were Randomized Controlled Trials (RCTs).

Actual evidence-based medicine is the tip of the iceberg among the different medical treatments available for the patient. An evidence map helps the practitioner to guide the therapeutic choices to more safe and efficient treatments. However, it does not fully address the need to tailor treatments to each patient’s unique circumstances, condition, or preferences (Subbiah, 2023).

Over the last six decades, the volume of scientific literature on cannabinoids and the endocannabinoid system (ECS) has grown exponentially. From a mere ten studies in 1962 to an overwhelming 4,428 by 2022, the field has seen a more than four-thousand-fold increase, highlighting an unmatched pace of discovery and investigation (NORML, 2022). As of 2024, approximately 11 new studies are published daily, with more than half bearing potential clinical relevance. This burgeoning body of evidence not only underscores the scientific community’s growing interest in cannabinoid-based therapeutics but also signals a paradigm shift in how we approach and manage chronic conditions.

Despite the existence of several studies and clinical experiences reporting therapeutic benefits using cannabis-based products, most of these studies do not yet present complete information and conclusive and extrapolable evidence on efficacy (European Monitoring Centre for Drugs and Drug Addiction, 2018; Whiting et al., 2015; Brazilian Health Regulatory Agency, 2024). Thus, there are very few cannabis-based products approved worldwide as medicines. Cannabis-based medicines are approved for treatment of seizures associated with two rare and severe forms of epilepsy (Lennox-Gastaut and Dravet syndrome) and tuberous sclerosis complex; and to improve symptoms related to muscle stiffness (spasticity) in multiple sclerosis (Brazilian Health Regulatory Agency, 2024; European Medicines Agency, 2024; Food and Drug Administration, 2024). Considering the gap of complete information on efficacy, in many countries, e.g., Germany, Portugal, Canada and Brazil, laws and regulatory standards that regulates cannabis and cannabis-based products in a specific regulatory category, different from the medicines category, have been approved in order to allow controlled and faster access to them (Brazilian Health Regulatory Agency, 2024; Germany, 2017; Infarmed, 2024; Health Canada, 2024).

The rapid accumulation of knowledge around the ECS and cannabinoid therapeutics presents opportunities and challenges for clinical practice. Despite CBD and Δ-9-THC being the most common defined formulations in this study, many new formulations and synthetic molecules are increasing their importance and clinical relevance. On the one hand, novel insights and emerging treatment trends offer the potential to enhance patient outcomes through more informed and discerning therapeutic decisions (Yang et al., 2021). On the other hand, the sheer volume and pace of new information necessitate a continuous and dynamic process of learning and adaptation for healthcare professionals (Gardiner et al., 2019). Optimizing patient outcomes with cannabinoid-based treatments is an evolving endeavor, one that will grow increasingly effective as evidence quality improves and experiences accumulate.

Beyond the quantitative and qualitative growth of cannabinoid research, a broader cultural shift is affecting the adoption and use of medical cannabis. Independent of legal restrictions, insurance policies, or medical advisories, patients worldwide are increasingly turning to cannabis-based products to alleviate their conditions (Marcu, 2020; Arboleda et al., 2020). This trend is driven by a global zeitgeist favoring patient autonomy and exploring alternative therapeutics, especially when conventional treatments fall short. The significant role of the ECS in modulating various chronic illnesses underscores the importance of understanding and leveraging cannabinoid-based products to achieve precise therapeutic effects, minimize adverse outcomes, and, ultimately, optimize patient care.

The evidence map presented in this study brings forth a comprehensive analysis of 194 systematic review studies on the effectiveness of medical cannabis across various health outcomes. The findings indicate a considerable number of positive and potentially positive effects, from the high-quality studies, particularly in areas such as pain relief, epilepsy, anxiety disorders, insomnia, cancer patients, muscle spasticity, urinary incontinence, anorexia and multiple sclerosis, among others.

Our findings of the most used medical cannabis formulations are in agreement with other scoping reviews interventions (Pantoja-Ruiz et al., 2022; Kirkland et al., 2022), as CBD and Δ-9-THC are the most popular and oldest formulations used. However, scoping reviews focusing in more specific areas and/or populations such as children and adolescents with autism spectrum disorder, for example, may have different majority formulations (Fletcher et al., 2022) due to the particularities of specific groups.

The diversity of outcomes is in accordance with what found in recent literature, likewise as the safety and adverse effects reported. Nonetheless, the qualities of the studies diverge due to the size of the research and the criteria used for classification (Pratt et al., 2019; Montero-Oleas et al., 2020).

While the evidence map offers valuable insights into the efficacy of medical cannabis, it also highlights the need for further high-quality research, particularly from underrepresented regions such as Latin America (Suárez-Jacobo et al., 2023). Enhancing the methodological quality of studies and increasing their number will provide a more robust foundation for clinical decision-making. It is also important to point out the importance to decrease the heterogeneity of formulations and studies in systematic reviews, as well as treat the differences between them more seriously, hence the high number of nonspecific formulations and populations found in this review.

Additionally, as the landscape of cannabinoid therapeutics continues to evolve, there is a critical need for comprehensive education for healthcare providers and patients (Ware and Ziemianski, 2015). Understanding the nuances of the ECS and the therapeutic potential of cannabinoids is essential for navigating the complexities of modern healthcare and ensuring that patients receive safe, effective, and personalized treatment options (Maccarrone et al., 2023).

Specific literature in different areas shows agreement in the heterogeneity of the findings concerning the use of medical cannabis, even in the same pathologies and treatments, due to the mixing of the findings and the quality of the studies (Pratt et al., 2019; Pantoja-Ruiz et al., 2022; Kirkland et al., 2022; Fletcher et al., 2022; Montero-Oleas et al., 2020).

As such, the evidence map on the effectiveness of medical cannabis serves as a crucial step forward in our understanding of cannabinoid-based therapeutics. However, it also underscores the necessity of continued research, education, and adaptation of an ever-expanding and evolving field. As we move forward, the collective goal should be to rationally harness the potential of cannabinoids to improve patient outcomes and advance the practice of healthcare in a rapidly changing world.

This Evidence Map embodies 194 systematic reviews regarding various uses of medical cannabis. The results highlight the use of various formulations based on cannabis and isolated CBD. Among the 71 health outcomes described in the systematic reviews, the most common were related to various types of pain and patient safety, followed by appetite, chemotherapy-induced nausea and vomiting, and muscle spasticity. Furthermore, 278 out of the 489 descriptions of a treatment effect for any of those 71 health outcomes reported “Positive” or “Potentially Positive” effects. Likewise, when analyses are restricted to AMSTAR 2 high-quality systematic reviews, 42 out of 67 descriptions of treatment effect reported “Positive” or “Potentially Positive” effects for up to 20 health outcomes, pain, insomnia, seizures, anxiety, muscle spasticity, multiple sclerosis, urinary incontinence, anorexia and patient safety, were among the most reported. The results of this map should highlight existing evidence and gaps, the need for additional studies providing confirmatory evidence on effectiveness for some clinical conditions, guide and facilitate decision-making for the clinical community worldwide and support the actions of health-related management for policymakers.