Cannabis Inflorescence for Medical Purposes: USP Considerations for Quality Attributes

Abstract

There is an active and growing interest in cannabis female inflorescence (Cannabis sativa) for medical purposes. Therefore, a definition of its quality attributes can help mitigate public health risks associated with contaminated, substandard, or adulterated products and support sound and reproducible basic and clinical research. As cannabis is a heterogeneous matrix that can contain a complex secondary metabolome with an uneven distribution of constituents, ensuring its quality requires appropriate sampling procedures and a suite of tests, analytical procedures, and acceptance criteria to define the identity, content of constituents (e.g., cannabinoids), and limits on contaminants. As an independent science-based public health organization, United States Pharmacopeia (USP) has formed a Cannabis Expert Panel, which has evaluated specifications necessary to define key cannabis quality attributes. The consensus within the expert panel was that these specifications should differentiate between cannabis chemotypes. Based on the secondary metabolite profiles, the expert panel has suggested adoption of three broad categories of cannabis. These three main chemotypes have been identified as useful for labeling based on the following cannabinoid constituents: (1) tetrahydrocannabinol (THC)-dominant chemotype; (2) intermediate chemotype with both THC and cannabidiol (CBD); and (3) CBD-dominant chemotype. Cannabis plants in each of these chemotypes may be further subcategorized based on the content of other cannabinoids and/or mono- and sesquiterpene profiles. Morphological and chromatographic tests are presented for the identification and quantitative determination of critical constituents. Limits for contaminants including pesticide residues, microbial levels, mycotoxins, and elemental contaminants are presented based on toxicological considerations and aligned with the existing USP procedures for general tests and assays. The principles outlined in this review should be able to be used as the basis of public quality specifications for cannabis inflorescence, which are needed for public health protection and to facilitate scientific research on cannabis safety and therapeutic potential.

Quantitative determination and validation of 17 cannabinoids in cannabis and hemp using liquid chromatography-tandem mass spectrometry

“…A candidate NRC certified reference material for cannabis was used for validation and quality control purposes. This material has been rigorously tested to be homogeneous and stable with respect to the 14 cannabinoids it contains, with value assignment for cannabinoids based on a combination of results from a validated LC-UV method [ 3 , 11 ] and a more targeted version of the LC-MS/MS method reported here that employs narrow calibration ranges that bracket the cannabinoid levels.…”

“…The lack of standardization in cannabis testing has resulted in a wide variety of methods being used, which has undoubtedly contributed to the high variability of results between testing laboratories [ 1 , 2 ]. However, associations such as AOAC, ASTM, and US Pharmacopeia [ 3 ] are working towards developing standardized methods to help resolve this issue.…”

“…While complete separation is possible for subsets of cannabinoids up to 8 or 12, LC-UV is generally not capable of resolving larger suites of cannabinoids. In some cases, the resolution of challenging cannabinoid pairs relies of precise pH control [ 11 ], but this can be problematic and limit the robustness of a method [ 3 ]. A fast, 5-min HPLC-DAD method [ 8 ] has been reported; however, the LOQ is high at 10 μg/mL, CBDA and most of the minor cannabinoids were not evaluated, and there is no evidence to indicate that many of the cannabinoids do not co-elute.…”

A narrative review of the ethnomedicinal usage of Cannabis sativa Linnaeus as traditional phytomedicine by folk medicine practitioners of Bangladesh

“…Furthermore, the usage of Cannabis for therapeutic purposes reported not to increase risk of harm to self or others (Walsh et al 2017), and the UN Commission on Narcotic Drugs already removed Cannabis and Cannabis resin from a category of the world's most dangerous substances (CND 2020; news.un.org/en/story/2020/12/1079132). Already, 33 states in the USA and several countries in the world have been using Cannabis for specific medical conditions (Sarma et al 2020). In June 2018, the US Food and Drug Administration (FDA) approved the first cannabis-derived medicine, Epidiolex® (cannabidiol, CBD), for the treatment of seizure disorders (Abu-Sawwa et al 2020).…”

Cannabis Contaminants Limit Pharmacological Use of Cannabidiol

“…As interest in Cannabis expands throughout the globe, many issues have arisen concerning the lack of cultivation standards and overall quality control of Cannabis products. Recently the United States Pharmacopeia (USP) formed a Cannabis Expert Panel, which has evaluated specifications necessary to define key Cannabis quality attributes including limits for contaminants including pesticide residues, microbial levels, mycotoxins, and elemental contaminants based on toxicological considerations and aligned with the existing USP procedures for general tests and assays (Sarma et al, 2020). Aside from inaccuracy in labeling phytocannabinoid content, it has been reported that Cannabis and derived products are often contaminated by microbes, heavy metals, pesticides, carcinogens, and debris, which must be addressed to ensure the safety of consumers (Table 1) (Mcpartland and Mckernan, 2017;Dryburgh et al, 2018).…”