Journal:Cannabis contaminants limit pharmacological use of cannabidiol

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Full article title Cannabis contaminants limit pharmacological use of cannabidiol
Journal Frontiers in Pharmacology
Author(s) Montoya, Zackary; Conroy, Matthieu; Vanden Heuvel, Brian D.; Pauli, Christopher S.; Park, Sang-Hyuck
Author affiliation(s) Colorado State University–Pueblo
Primary contact Email: sanghyuck dot park at csupueblo dot edu
Editors Khan, Tanveer A.
Year published 2020
Volume and issue 11
Article # 571832
DOI 10.3389/fphar.2020.571832
ISSN 1663-9812
Distribution license Creative Commons Attribution 4.0 International
Website https://www.frontiersin.org/articles/10.3389/fphar.2020.571832/full
Download https://www.frontiersin.org/articles/10.3389/fphar.2020.571832/pdf (PDF)

Abstract

For nearly a century, cannabis has been stigmatized and criminalized across the globe, but in recent years, there has been a growing interest in cannabis due to the therapeutic potential of phytocannabinoids. With this emerging interest in cannabis, concerns have arisen about the possible contaminations of hemp with pesticides, heavy metals, microbial pathogens, and carcinogenic compounds during the cultivation, manufacturing, and packaging processes. This is of particular concern for those turning to cannabis for medicinal purposes, especially those with compromised immune systems. This review aims to provide types of contaminants and examples of cannabis contamination using case studies that elucidate the medical consequences consumers risk when using adulterated cannabis products. Thus, it is imperative to develop universal standards for cultivation and testing of products to protect those who consume cannabis.

Keywords: cannabis, cannabidiol, cannabis contaminants, hemp, phytocannabinoids

Introduction

Phytocannabinoids have garnered global attention recently due to the therapeutic potentials in Parkinson’s disease[1], schizophrenia[2], cancers[3][4], pain, anxiety, depression, and other neurological disorders[5], as well as the Food and Drug Administration (FDA) approval of Epidiolex for Dravet syndrome[6] and Lennox-Gauss Syndrome.[7] As of 2019, a total of 33 states, the District of Columbia, Guam, Puerto Rico, and the U.S Virgin Islands have approved cannabis for medicinal purposes, and 21 states are considering bills that would decriminalize it under legislative action. With recent legalization in Canada in 2019, more countries are beginning to question the rationale behind criminalizing cannabis.[8] As interest in cannabis expands around 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 such as pesticide residues, microbial pathogen levels, mycotoxins, and elemental contaminants, based on toxicological considerations and aligned with the existing USP procedures for general tests and assays.[9] 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).[10][11]


Tab1 Montoya FrontPharm2020 11.jpg

Table 1 List of cannabis contaminants and sources, target/mechanism, and its respective risks to human health. GABA = γ-amino butyric acid.

These contaminants are imminent threats that directly impact public health and wellness, particularly to the immunocompromised and pediatric patients who take cannabis products as a treatment for numerous human disorders, including cancer patients and those suffering from epileptic seizures.[12] To increase public awareness, we provide examples of contamination, its medical consequences reported in clinical research, and then suggest that each risk category be analyzed for best practices to limit exposure of contaminants to the consumer. We recommend hemp producers, manufacturers, medical professionals, and legislators recognize this risk and establish regulatory measures to educate the public and lessen the adverse effects caused by the contaminants in cannabis, particularly in cannabidiol (CBD)-based products.

Labeling inaccuracy

Mislabeling of phytocannabinoid profiles in CBD products is one of the major concerns to consumers.[13] Inaccurate reporting of the cannabinoid content risks exposing medicinal users to phytocannabinoids of which they have no intent to consume, namely Δ-9-tetrahydracannabinol (THC).[14] This is of particular concern within pediatric patients, as THC intoxication has been shown to alter development of white matter in the brain[15], affect cognitive functioning[16][17], and affect learning and memory within adolescents.[18]

Despite some U.S. states like Colorado having a 15% allowable reporting variance of the phytocannabinoid content on CBD product labels[19], measured contents often exceed this range. For example, a recent study shows that 69% of 84 CBD products purchased from 31 American online retailers were inaccurately labeled for CBD: 26% were overlabeled, whereas 42% were underlabeled for CBD concentration.[20] Additionally, 64% of 14 CBD products sold in the European Union (EU) market presented different cannabinoid profiles from the declared amount.[21] Inaccuracies are also found on labels of hemp-type cannabis sold in the Netherlands, with measured THC and CBD deviating from label claims by 8%–99% in CBD oil samples obtained from patients.[13] In Germany, an analysis of 67 CBD product samples found that 25% of samples were contaminated with residual THC above the lowest level of observable effects, or the lowest level that is known to cause physiological effects in humans (2.5 mg/day).[22] In a recent analysis of 25 CBD oil products purchased in Mississippi, only three of the 25 were within ±20% of label claim, 15 were below the stated claim for CBD, two exceed these claims by more than 50%, and THC content for three products exceeded the 0.3% legal limit.[23]

There are also concerns for edible cannabis products (e.g., gummies, cookies, etc.) containing under- and overreported phytocannabinoid content, specifically THC.[24] In states where cannabis is legal for recreation, these edible products are tested for overall THC potency in addition to dose-specific potency of THC to be sure these products stay under 100 mg total THC with no more than 10 mg of THC per dose.[25] However, in hemp, there is no regulating body overseeing this testing, therefore the responsibility to test CBD edibles is left to each product manufacturer to ensure compliance of cannabinoid content limits, which is often neglected.[25] While currently CBD and THC are the only cannabinoids required to be labeled, it may be beneficial to include the profile of acidic forms of THC and CBD, as well as some representative minor cannabinoids such as cannabigerol (CBG), cannabichromene (CBC), or possibly some of the short chain versions of these referred to as "-varin cannabinoids" (e.g., tetrahydrocannabivarin [THCV] and cannabidivarin [CBDV]) on these labels. These minor cannabinoids are shown to have some therapeutic effects that could be enhanced in combination with other major cannabinoids.[26]


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Notes

This presentation is faithful to the original, with only a few minor changes to presentation. Some grammar and punctuation was cleaned up to improve readability. In some cases important information was missing from the references, and that information was added. The original article lists references in alphabetical order; this version lists them in order of appearance, by design. A citation for Gorai et al. is found in the original references and in Table 1, but it is not included in-line in the original text; it has been inserted where it should presumably go for this version.