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      Safety and risks of CBD oils purchased online: unveiling uncertain quality and vague health claims

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          Abstract

          Introduction: The unmet need for highly effective, naturally derived products with minimal side effects results in the over-popularity of ever-newer medicinal plants. In the middle of 2010, products containing cannabidiol (CBD), one of the special metabolites of Cannabis sativa, started to gain popularity. For consumers and healthcare providers alike, the legal context surrounding the marketing of CBD products is not entirely clear, and the safety of using some products is in doubt. Companies in the online medicinal product market profit from the confusion around CBD oils.

          Methods: In our study, we employed a complex method known as risk-based safety mapping of the online pharmaceutical market, which included health claim content analysis of online stores, test purchases, and labeling and quantitative analysis of the CBD content.

          Results: There were discovered 16 online retailers selling an average of 2–7 goods and CBD oils with a concentration of 3%–5% (30–50 mg/mL) CBD. The majority (n/N = 10/16, 62.5%) displayed potential health-related benefits indirectly on their website, and in the case of one web shop (n/N = 1/16, 6.3%), we detected COVID-19-related use. Altogether, 30 types of purported “indications” were collected. A total of 12 CBD oil products were test-purchased from online retailers in December 2020. Upon evaluating the packaging and product information, we noticed that three products (n/N = 3/12, 25%) lacked instructions on use, hence increasing the risk of inappropriate application and dosing. The cannabidiol content was quantified using UHPLC. The measured CBD concentrations of the products ranged from 19.58 mg/mL to 54.09 mg/mL (mean 35.51 mg/mL, median 30.63 mg/mL, and SD ± 12.57 mg/mL). One (8.33%) product was underlabeled, five (41.67%) were over-labeled, and only every second product (50%) was appropriately labeled based on the quantitative assessment of CBD concentration.

          Discussion: Further research and quality control are necessary to establish the regulatory context of the usage and classification of CBD and other cannabinoids in nonmedicinal products (e.g., food supplements), as authorities and policymakers worldwide struggle with the uncertainties surrounding CBD products.

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          Most cited references56

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          Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.

          Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.
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            Cannabidiol Adverse Effects and Toxicity

            Background: Currently, there is a great interest in the potential medical use of cannabidiol (CBD), a non-intoxicating cannabinoid. Productive pharmacological research on CBD occurred in the 1970s and intensified recently with many discoveries about the endocannabinoid system. Multiple preclinical and clinical studies led to FDA-approval of Epidio-lex®, a purified CBD medicine formulated for oral administration for the treatment of infantile refractory epileptic syndromes, by the US Food and Drug Administration in 2018. The World Health Organization considers rescheduling can-nabis and cannabinoids. CBD use around the world is expanding for diseases that lack scientific evidence of the drug’s effi-cacy. Preclinical and clinical studies also report adverse effects (AEs) and toxicity following CBD intake. Methods: Relevant studies reporting CBD’s AEs or toxicity were identified from PubMed, Cochrane Central, and EMBASE through January 2019. Studies defining CBD’s beneficial effects were included to provide balance in estimating risk/benefit. Results: CBD is not risk-free. In animals, CBD AEs included developmental toxicity, embryo-fetal mortality, central nerv-ous system inhibition and neurotoxicity, hepatocellular injuries, spermatogenesis reduction, organ weight alterations, male reproductive system alterations, and hypotension, although at doses higher than recommended for human pharmacotherapies. Human CBD studies for epilepsy and psychiatric disorders reported CBD-induced drug-drug interactions, hepatic abnormal-ities, diarrhea, fatigue, vomiting, and somnolence. Conclusion: CBD has proven therapeutic efficacy for serious conditions such as Dravet and Lennox-Gastaut syndromes and is likely to be recommended off label by physicians for other conditions. However, AEs and potential drug-drug interactions must be taken into consideration by clinicians prior to recommending off-label CBD.
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              Labeling Accuracy of Cannabidiol Extracts Sold Online

              This study compares ingredients listed on the labels of cannabidiol products sold online to actual product constituents determined by laboratory analysis.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/838903/overviewRole: Role:
                Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2517591/overviewRole: Role: Role:
                URI : https://loop.frontiersin.org/people/2215529/overviewRole: Role: Role:
                URI : https://loop.frontiersin.org/people/508894/overviewRole: Role: Role:
                URI : https://loop.frontiersin.org/people/1635998/overviewRole: Role: Role: Role: Role: Role:
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                14 December 2023
                2023
                : 14
                : 1273540
                Affiliations
                [1] 1 Department of Pharmaceutics , Faculty of Pharmacy , University of Pécs , Pécs, Hungary
                [2] 2 Institute of Pharmacognosy , Faculty of Pharmacy , University of Szeged , Szeged, Hungary
                [3] 3 Institute of Clinical Pharmacy , Faculty of Pharmacy , University of Szeged , Szeged, Hungary
                [4] 4 Institute for Translational Medicine , Medical School , University of Pécs , Pécs, Hungary
                Author notes

                Edited by: Diego Romano Perinelli, University of Camerino, Italy

                Reviewed by: Nadezhda A. German, Texas Tech University Health Sciences Center, United States

                Cristina Ramirez, National University of Mar del Plata, Argentina

                *Correspondence: András Fittler, fittler.andras@ 123456pte.hu
                Article
                1273540
                10.3389/fphar.2023.1273540
                10773908
                38192407
                982febd6-c9d7-4e65-9276-994b42c88b2d
                Copyright © 2023 Vida, Strauss, Bajtel, Kiss, Csupor and Fittler.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 August 2023
                : 27 November 2023
                Funding
                The authors declare that financial support was received for the research, authorship, and/or publication of this article. This research was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00238/20/5) and the Hungarian Scientific Research Fund OTKA grant (NKFI-ID 143684). The financial support of the National Research, Development and Innovation Office (2021-1.2.6-TÉT-IPARI-MA-2022-00021) is gratefully acknowledged.
                Categories
                Pharmacology
                Original Research
                Custom metadata
                Ethnopharmacology

                Pharmacology & Pharmaceutical medicine
                cannabidiol oil,cannabidiol,consumer product safety,online medicinal products,product labeling,quality,test purchase

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