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Pharmaceutical Evaluation of Medical Cannabis Extracts Prepared by Artisanal and Laboratory Techniques

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Abstract

The popularity of Cannabis extracts in the treatment of hard-to-manage clinical conditions and the lack of access to pharmaceutical grade Cannabis products have impacted the increase of clandestine and artisanal product consumption in Brazil. Currently, hundreds of judicial authorizations for Cannabis cultivation and artisanal extract preparation have been granted in Brazil. To evaluate the artisanal preparation techniques and improve Cannabis extract quality, preparations by patients were monitored between 2017 and 2022, and a preparation method by supercritical fluid extraction was developed. Between 2017 and 2018, the most common technique used by participants was the decoction of flowers in heated oil that provided extracts with low cannabinoid levels and the predominance of acid cannabinoids as well as high microbiological contamination. Between 2019 and 2022, decarboxylation by heating and extraction by maceration in ethanol were tested to decrease the microbiological contamination and increased the neutral cannabinoid levels in the extracts. Cannabidiol levels measured in 2021 (26.0 ± 31.1 mg/g) and 2022 (42.9 ± 15.5 mg/g) in the extracts prepared at home with pharmaceutical support were similar to industrial products and higher in cannabinoids than the products supplied by non-governmental organizations. Cannabis extracts prepared by supercritical fluid extraction at 50 °C at a pressure of 15 MPa and 800 g CO2 for 15–24 min from 9–24 g decarboxylated Cannabis flower provided cannabidiol recoveries  > 80%. Soxhlet extraction, used as a comparison method, showed excellent recoveries and is a low-cost alternative technology that is feasible to implement in community pharmacies.

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References

  • Anvisa (2010) Farmacopeia brasileira 5a ed. Agência Nacional de Vigilância Sanitária. Brasília

  • Arzimanoglou A, Brandl U, Cross JH, Gil-Nagel A, Lagae L, Landmark CJ, Specchio N, Nabbout R, Thiele EA, Gubbay O, The Cannabinoids International Experts Panel (2020) Epilepsy and cannabidiol: a guide to treatment. Epileptic Disord 22:1–14. https://doi.org/10.1684/epd.2020.1141

  • Booth JK, Yuen MMS, Jancsik S, Madilao LL, Page AJE (2020) Terpene synthases and terpene variation in Cannabis sativa. Plant Physiol 184:130–147. https://doi.org/10.1104/PP.20.00593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carvalho VM, Aguiar A, Baratto L, Souza F, Rocha E (2020) Quantificação de canabinoides em extratos medicinais de Cannabis por cromatografia líquida de alta eficiência.Quim Nova 43:90–97. https://doi.org/10.21577/0100-4042.20170457

  • Carvalho VM, Almeida FG, Aguiar AFL, Pereira FCS, Rocha ED (2021) Facing the forensic challenge of Cannabisregulation : a methodology for the differentiation between hemp and marijuana samples. Braz J Anal Chem 9:162–176. https://doi.org/10.30744/brjac.2179-3425.AR-42-2021

  • Carvalho VM, AlmeidaFG, Macêdo Vieira AC, Rocha ED, Cabral LM, Strongin RM (2022) Chemical profiling of Cannabis varieties cultivated for medical purposes in southeastern Brazil. Forensic Sci Int 335:111309.https://doi.org/10.1016/j.forsciint.2022.111309

  • INMETRO (2020) Orientação sobre Validação de Métodos Analíticos- DOQ-CGCRE-008. Instituto Nacional de Metrologia, Normalização e Qualidade Industrial, Brasil

  • ISO (2017) International Standard Organization. General requirements for the competence of testing and calibration laboratories, ISO/IEC 17025

  • Jin D, Dai K, Xie Z, Chen J (2020) Secondary metabolites profiled in Cannabis inflorescences, leaves, stem barks, and roots for medicinal purposes. Sci Rep 10:339. https://doi.org/10.1038/s41598-020-60172-6

    Article  CAS  Google Scholar 

  • Kargili U, Ayataç E (2022) Supercritical fluid extraction of cannabinoids (THC and CBD) from four different strains of Cannabis grown in different regions. J Supercrit Fluids 179:105410. https://doi.org/10.1016/j.supflu.2021.105410

  • Lovestead TM, Bruno TJ (2017) Determination of cannabinoid vapor pressure to aid in vapor phase detection of intoxication. Forensic Chem 5:79–85. https://doi.org/10.1016/j.forc.2017.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mead A (2017) The legal status of Cannabis (marijuana) and cannabidiol (CBD) under U.S. law. Epilepsy Behav 70:288–291. https://doi.org/10.1016/j.yebeh.2016.11.021

    Article  PubMed  Google Scholar 

  • Mohammedi-Ameur S, Dahmane M, Brera C, Kardjadj M, Ben-Mahdi MH (2020) Occurrence and seasonal variation of aflatoxin M1 in raw cow milk collected from different regions of Algeria. Vet World 13:433–439. https://doi.org/10.14202/vetworld.2020.433-439

  • Monton C, Chankana N, Leelawat S, Suksaeree J, Songsak T (2022) Optimization of supercritical carbon dioxide fluid extraction of seized Cannabis and self-emulsifying drug delivery system for enhancing the dissolution of cannabis extract. J Supercrit Fluids 179:105423. https://doi.org/10.1016/j.supflu.2021.105423

  • Porcari GS, Fu C, Doll ED, Carter EG, Carson RP (2018) Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: practical experiences in a tertiary medical center. Epilepsy Behav 80:240–246. https://doi.org/10.1016/j.yebeh.2018.01.026

    Article  PubMed  Google Scholar 

  • Romero P, Peris A, Vergara K, Matus JT (2020) Comprehending and improving cannabis specialized metabolism in the systems biology era. Plant Sci 298:110571. https://doi.org/10.1016/j.plantsci.2020.110571

  • Sarma ND, Waye A, ElSohly MA, Brown PN, Elzinga S, Johnson HE, Marles RJ, Melanson JE, Russo E, Deyton L, Hudalla C, Vrdoljak GA, Wurzer JH, Khan IA, Kim NC, Giancaspro GI (2020) Cannabis inflorescence for medical purposes: USP considerations for quality attributes. J Nat Prod 83:1334–1351. https://doi.org/10.1021/acs.jnatprod.9b01200

    Article  CAS  PubMed  Google Scholar 

  • Thiele EA, Marsh ED, French JA, Mazurkiewicz MB, Benbadis SR, Joshi C, Lyons PD, TaylorA RC, Sommerville K, Gunning B, Gawlowicz J, Lisewski P, Mitosek Szewczyk K, Steinborn B, Zolnowska M, Hughes E, McLellan A, Benbadis S, Wilfong A (2018) Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 391:1085–1096. https://doi.org/10.1016/S0140-6736(18)30136-3

    Article  CAS  PubMed  Google Scholar 

  • USP (2016a) “Elemental Impurities in Pharmaceutical Materials – Procedures,” The United States Pharmacopeia (USP) Rockville: U.S. Pharmacopeia

  • USP (2016b) “Elemental Impurities – Limits”; The United States Pharmacopeia (USP). 39

  • Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S, Westwood M, Kleijnen J (2015). Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 313:2456–2473. https://doi.org/10.1001/jama.2015.6358

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Acknowledgements

We are grateful for the financial support from the Serrapilheira Institute (grant number Serra-1709-18891), Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPQ, Brazil (Process Number-426406/2018-4), and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (process number-E26/010.101037/2018).

Funding

This work was supported by the Serrapilheira Institute (grant number Serra-1709-18891), by Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPQ, Brazil (Process Number-426406/2018-4), and by Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (Process Number-E26/010.101037/2018).

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Authors

Contributions

VMC coordinated the research and was responsible for conceptualization, funding acquisition, statistical analysis, writing original draft, review, and editing. VMC also supervised the development of the GC-MS, HPLC, and SFE methodologies, and supervised the monitoring of the crops and Cannabis extract preparation at patients’ home. JSC performed the microbiological analysis and microbiological data processing, and helped in the writing of original draft and review. JSC also contributed in the monitoring of the crops and Cannabis extract preparation at patients’ home. JABF supervised the microbiological analysis and resources of the microbiological laboratory. LMGS performed the metal analysis and data processing and contributed in the writing of original draft and review. SCJ supervised resources and metal analysis. FGA performed the validation of the cannabinoid quantification method in plants and contributed in the monitoring of the crops and Cannabis extract preparation at patients’ home. EDR developed the methodologies for quantification of terpenes and cannabinoids, performed the SFE study, and contributed in the monitoring of the crops and Cannabis extract preparation at patients’ home. AMV contributed in the monitoring of the crops and Cannabis extract preparation at patients’ home. AJRS supervised the SFE study and contributed in writing original draft and review. RMS contributed in the writing original draft and review.

Corresponding author

Correspondence to Virgínia Martins Carvalho.

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Ethical Approval

The present study was approved by the Ethics Committee of the Clementino Fraga Filho Hospital, Rio de Janeiro, Brazil, Number 2021817.0.00005257.

Competing Interests

The authors declare no competing interests.

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Carvalho, V.M., dos Santos Carmo, J., dos Santos, L.M.G. et al. Pharmaceutical Evaluation of Medical Cannabis Extracts Prepared by Artisanal and Laboratory Techniques. Rev. Bras. Farmacogn. 33, 724–735 (2023). https://doi.org/10.1007/s43450-023-00412-8

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