Clinical studies on the effects of cannabinoids and cannabis-based products have been hindered, in large part, by their classification as Schedule I drugs under the Controlled Substances Act. In the United States, it is possible to conduct patient studies using cannabinoids; however, strict regulations regarding access to federally regulated cannabis approved for research purposes have curtailed large-scale efforts.
Likewise, studies comparing the efficacy of different cannabinoid formulations have been limited by the absence of a diverse array of FDA-approved products containing delta-9-tetrahydrocannabinol (THC). Federal restrictions and the lack of cohesive guidelines for gathering and analyzing patient and consumer data continue to hinder the understanding of the effect of cannabinoids by type.
Regulatory Environment Hinders Research Efforts
Although researchers can gather subjective data on consumer experiences with cannabis provided no medical claims are made, such studies pose a challenge for robust statistical analysis. Consumer research is not usually controlled, relies on self-reporting and does not consistently consider different dosages, cannabinoid profiles, or routes of administration. Different methods have been employed to estimate cannabis dosing based on the weight of input material and route of administration, traditionally based on inhalation as the route of administration.1
Such methods, however, do not necessarily provide an accurate account of cannabinoid dose or quantity consumed, individual variation in drug tolerance, the time interval between dosing, different effects of various cannabinoids, or the influence that combined alternative routes (eg, oral, topical applications) have on patient treatment and consumer experience outcomes.2 Given the high degree of variability in use, product type, dosage, and cannabinoid representation, normalization of dosing values for cannabis product-use studies has proven difficult.
Research Tool Aims To Quantify Cannabinoid Exposure
A recent scientific report published in Nature by Lambros et al.,3 “CannaCount: an improved metric for quantifying estimates of maximum possible cannabinoid exposure,” seeks to standardize quantification of cannabis use by considering the heterogeneity of available data.3 The authors developed CannaCount, a metric that uses consumer responses to a guided interview questionnaire to provide an estimated quantification of maximum possible cannabinoid exposure across various product types based on specific cannabinoid concentrations, frequency and quantity of each product used.
The metric accounts for 4 separate routes of administration—inhaled, oral, mucosal, and topical. As a single value is useful when comparing heterogeneous data inputs across a wide range of cannabis users and products, an additional step in the algorithm allows for a single-value determination across all possible routes of administration by calculating a singular estimate based on the maximum possible exposure to individual cannabinoids.
A 2-year longitudinal study was conducted using CannaCount to calculate THC and cannabidiol (CBD) exposure in 60 medical patients. Data collected included product type, cannabinoid concentration, duration, frequency, and amount of product consumed. The authors quantified THC and CBD exposure through the CannaCount algorithm using 1 of 2 methods based on available product information.
The “discrete-use approach” quantifies individual cannabinoid content using data from product testing reports (ie, the total number of uses averaged over the time interval between use to determine exposure). The “total-use approach,” derives exposure based on the total amount of cannabinoids in each product used, averaged over the time interval of use. Although not addressed in the study, maximum exposure to every cannabinoid present in each product can be estimated using the approach above if individual cannabinoids have quantified test results available on the package labeling.
The CannaCount algorithm, which relies on responses to an extensive interview process and derives values from a computational model, might appear laborious to some users. This metric, however, provides more robust data, considers more variables than previous approaches and derives more accurate information on total cannabinoid exposure over time based on currently available product data.
Therefore, CannaCount should prove a valuable tool for determining the effects of different cannabinoids and mixtures of cannabinoids at varying doses, durations of use, and other routes of administration with respect to specific patient and consumer outcomes.
A relatively simple software solution based on the CannaCount questionnaire and computational algorithms would streamline the data entry and analysis process, creating a standardized approach for additional, larger patient and consumer studies and permitting meaningful cross-study comparison to derive robust, outcome-based statistical analysis. Such a solution could advance medical cannabis research and assist in developing consumer product formulations.
Although CannaCount is more accurate and addresses more variables than previous methods, it does not provide actual pharmacokinetic data or assist in determining the bioavailability of cannabinoids in each product. Therefore, well-controlled clinical studies of individual products are required to obtain this information.
- Wetherill RR, Hager N, Guthier E, Franklin, TR. Gram years, a method to standardize and quantify lifetime cannabis consumption. Cannabis Cannabidiol Res. 2016;1(1):216-217. doi:10.1089/can.2016.0025.
- Freeman TP, Lorenzetti V. “Standard THC units”: a proposal to standardize dose across all cannabis products and methods of administration. Addiction. 2020;115(7):1207-1216. doi:10.1111/add.14842
- 3. Lambros AM, Sager KA, Dahlgren MK, et al. CannaCount: an improved metric for quantifying estimates of maximum possible cannabinoid exposure. Sci Rep. 2023;13(1):5869. doi:10.1038/s41598-023-32671-9