The Cannabis and Health Research Initiative will help integrate medicinal cannabis in healthcare

In the USA, there are more than 5.5 million registered patients in state-regulated medicinal cannabis programs and many people use hemp products (sourced from cannabis containing <0.3% delta-9-tetrahydrocannabinol (THC) by dry weight) for therapeutic purposes. However, clinical research on non-pharmaceutical cannabis products remains limited¹, healthcare providers feel inadequately trained on integrating medicinal cannabis into their practice², and medicinal cannabis use is poorly documented in electronic medical records (EMRs)³. These issues highlight the need for patient-level data on the impacts of medicinal cannabis use⁴.

With legalization of retail cannabis sales in some US states, the diversity of cannabis products available to consumers has substantially increased⁵. Products vary in chemical composition⁶, dose and intended route of administration, all of which can affect clinical effect, safety and abuse liability, and should be considered in clinical decision making. The diversity in cannabis products and the use of poorly defined nomenclature contributes to difficulty in assessing the health effects of medicinal cannabis.

At a minimum, cannabis products should be categorized (Table 1) and included in epidemiological surveys and EMRs. Without improved nomenclature, existing data sources will remain insufficient to capture health-related impacts of medicinal cannabis use.

Table 1 |.

Categorization of cannabis products

Categorization	Type
Cannabis product chemotype	Δ9-THC-dominant
	Cannabidiol (CBD)-dominant
	Balanced Δ9-THC and CBD
	Minor cannabinoid-dominant
Route of administration	Inhaled
	Ingested
	Topically applied
	Inserted suppository

The cannabis industry and advocacy messaging commonly promote the use of cannabis products to treat various conditions such as mental health disorders (such as depression, anxiety and post-traumatic stress disorder), cancer, seizure disorders, pain and sleep disorders. Despite the widespread application of cannabis as a therapeutic, studies on the efficacy of cannabis products are mixed and are further limited by a dearth of prospective studies and heterogeneity of products used⁷. Research into the safety and efficacy of medicinal cannabis use, by product type, across health conditions for which patients are seeking benefit from cannabis is urgently needed.

Another layer of complexity in understanding the health effects of medicinal cannabis is the questionable quality control of retail products. There are no industry standards or federal regulations about manufacturing practices, product labeling, or analytical test methods in the USA. Studies have repeatedly demonstrated shortcomings in the accuracy of dose labels and the detection of harmful contaminants in retail cannabis⁸. Inaccurate product labeling and large ranges in drug concentration among products make it difficult for consumers to elicit desired medicinal benefits in the case of over-labeling of low-concentration products, and increase the risk of adverse effects in the case of under-labeling of high-concentration products. There is a need for the establishment of quality assurance regulations and product testing commensurate with requirements for other medications, to reduce unintended consequences associated with product contamination and mislabeling and facilitate precise dosing recommendations by treatment providers.

Large-scale, randomized clinical trials are the gold standard for assessing the safety and effectiveness of pharmacological treatments. However, clinical trials can be limited by the sample populations (which may not be representative of the general public) and high costs. In the case of medicinal cannabis, a clinical trial with a single product may not generalize to other cannabis products⁹. Alternative methods that can provide large amounts of patient-level data over extended periods of time are critically needed to evaluate the health effects of cannabis products defined by their chemotype, dose and route of administration. Longitudinal observational patient registries and analyses of EMRs are two approaches that can track health outcomes at scale.

Patient registries provide organized systems that track large-scale uniform data using observational methods, which can be used to examine cohorts of patients based on health conditions, cannabis product type, or other categories of interest¹⁰. Registries also enable the examination of large, heterogeneous patient populations owing to broader inclusion criteria, leading to greater generalizability of findings. Because patients may not be able to accurately recall precise diagnoses or medication prescription details and may not have access to medical assessments or clinical test results, a complimentary source of data is EMRs. Computer science technology and the widespread adoption of EMRs, with standardization of medical coding, provides large-scale, detailed patient-level information on demographics, health, treatment history, medication use and healthcare utilization over time. EMR documentation can provide meaningful insight into the benefits and adverse outcomes associated with medications, as well as provide cross-sectional and longitudinal comparisons with matched controls.

Complimentary utilization of longitudinal observational research with analysis of EMRs provides a relatively complete picture of the natural history of patient experience with the medicinal use of cannabis. As such, we encourage all health systems and providers to discuss cannabis use with their patients and record whether a patient is using medicinal cannabis, defined by chemotype, dose and route of administration, in patient EMRs to facilitate research. This information can be captured in clinical notes, but we also encourage health systems to develop and implement the use of formal flowsheets or smartforms in EMRs, or to collect this information via patient-reported questionnaires linked to EMRs before scheduled appointments.

It is through data and resource sharing that the scientific advances needed to ascertain whether and how to integrate cannabis into medical practice are going to be accomplished. Collaborations between researchers, health systems and government entities who have conducted studies or collected data related to the health effects of medicinal cannabis use, patients who engage in medicinal cannabis use, or cannabis product characterization will be key to generate better evidence in this crucial area with substantial implications for public health.

The authors are currently establishing the Cannabis and Health Research Initiative (CHRI), a project aimed at better understanding the health effects of medicinal cannabis use. CHRI is funded by a National Institutes of Health (NIH) grant (UM1-DA059000) and is being built as a transdisciplinary platform for engagement by multiple stakeholders and will include prospective data collection with medicinal cannabis patients, cannabis product surveillance, a data repository for researcher access, development of ‘big data’ tools for probing EMRs, and dissemination of findings to scientists, healthcare providers, policymakers and the public. This work compliments similar state-funded initiatives in California, Colorado, Florida, Kentucky and Michigan. Collaboration across entities and engagement from additional stakeholders is strongly encouraged to maximize the return on investment and advancement of medicinal cannabis science.

Results of this type of collaborative research agenda can help inform clinical decisionmaking related to the initiation of medicinal cannabis, provide guidance related to product, route of administration and dose selection, and improve data on adverse events, injury and poisoning risk, and abuse liability of specific cannabis products across the spectrum of therapeutic use. Findings will also help government agencies to develop effective regulatory strategies to mitigate harms associated with the rapidly growing cannabis industry. With sufficient collaborative engagement, research can improve the evidence base for medicinal cannabis use, help to steer the integration of cannabis in medicine in the short term, and guide the development of novel cannabinoid therapeutics in the long-term.