Medicinal Cannabis: Extended Stability of Cannabis Extracts Produced Using a New Ethanol-based Extraction Method

Abstract

Cannabis as a therapeutic agent is increasing in popularity all around the globe, particularly in Western countries, and its potential is now well assessed. On the other hand, each country has its own regulation for the preparation of cannabis macerated oils; in Italy, there are only a few preparation methods allowed. With this work, we aim to perform a stability study of cannabis oils produced with a novel method for the extraction of cannabinoids from cannabis inflorescence. Three different varieties of cannabis were used, with and without the adding of tocopherol acetate as an antioxidant. Cannabinoids were extracted using ethanol at room temperature; then, the solvent was evaporated under reduced pressure and the preparations reconstituted with olive oil. In this work, we assessed the stability of both cannabinoids and terpenes in these formulas over 8 months. Cannabinoid stability was assessed by monitoring the concentrations of THC and CBD, while terpene stability was assessed by monitoring β-Caryophyllene and α-Humulene concentrations. Stability of the extracts was not influenced by the presence of tocopherol acetate, though refrigeration seems to be detrimental for a long storage of products, especially regarding THC concentrations. The improvements offered by this method reside in the flexibility in controlling the concentration of the extract and the ability to produce highly concentrated oils, alongside the possibility to produce standardized oils despite the variability of the starting plant material.

Key words

Cannabis - Cannabaceae - stability - macerated oils - extraction - galenic formulas

Publikationsverlauf

Eingereicht: 28. April 2023

Angenommen nach Revision: 28. September 2023

Artikel online veröffentlicht:
14. November 2023

• References

• 1 Klumpers LE, Thacker DL. A brief background on cannabis: From plant to medical indications. J AOAC Int 2019; 102: 412-420
• 2 Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 2013; 33: 195-209
• 3 Baron EP. Medicinal properties of cannabinoids, terpenes, and flavonoids in cannabis, and benefits in migraine, headache, and pain: An update on current evidence and cannabis science. Headache 2018; 58: 1139-1186
• 4 Thomas BF, ElSohly MA. The analytical chemistry of cannabis: Quality assessment, assurance, and regulation of medicinal marijuana and cannabinoid preparations. Amsterdam: Elsevier; 2016: 27-41
• 5 Lorenzin Decreto 9 Novembre 2015 (GU 30. 11.2015). 2015: 16 – 25.
• 6 Dei Cas M, Arnoldi S, Monguzzi L, Casagni E, Morano C, Vieira de Manincor E, Bolchi C, Pallavicini M, Gambaro V, Roda G. Characterization of chemotype-dependent terpenoids profile in cannabis by headspace gas-chromatography coupled to time-of-flight mass spectrometry. J Pharm Biomed Anal 2021; 203: 114-180
• 7 Pertwee RG. Pharmacological actions of cannabinoids. Handb Exp Pharmacol 2005; 168: 1-51
• 8 Russo EB. Cannabis therapeutics and the future of neurology. Front Integr Neurosci 2018; 12: 51
• 9 Morano C, Dei Cas M, Roda G, Fabbriconi A, Casagni E, Pallavicini M, Bolchi C, Pallotti G, Romaniello F, Rovellini P. The antioxidant role of hemp phytocomplex in cannabis oil-based extracts. Pharmaceuticals 2022; 15: 1-8
• 10 Bolchi C, Pallavicini M, Casagni E, Vieira de Manincor E, Gambaro V, Dei Cas M, Roda G. Development and early identification of cannabis chemotypes during the plant growth: Current analytical and chemometric approaches. Anal Sci 2021; 37: 1665-1673
• 11 Dei Cas M, Casagni E, Casiraghi A, Minghetti P, Fornasari DMM, Ferri F, Arnoldi S, Gambaro V, Roda G. Phytocannabinoids profile in medicinal cannabis oils: The impact of plant varieties and preparation methods. Front Pharmacol 2020; 11: 1752
• 12 Romano LL, Hazekamp A. Cannabis oil: Chemical evaluation of an upcoming cannabis-based medicine. Cannabinoids 2013; 1: 1-11
• 13 Citti C, Ciccarella G, Braghiroli D, Parenti C, Vandelli MA, Cannazza G. Medicinal cannabis: Principal cannabinoids concentration and their stability evaluated by a high performance liquid chromatography coupled to diode array and quadrupole time of flight mass spectrometry method. J Pharm Biomed Anal 2016; 128: 201-209
• 14 Casiraghi A, Roda G, Casagni E, Cristina C, Musazzi UM, Franzè S, Rocco P, Giuliani C, Fico G, Minghetti P, Gambaro V. Extraction method and analysis of cannabinoids in cannabis olive oil preparations. Planta Med 2018; 84: 242-249
• 15 Calvi L, Pentimalli D, Panseri S, Giupponi L, Gelmini F, Beretta G, Vitali D, Bruno M, Zilio E, Pavlovic R, Giorgi A. Comprehensive quality evaluation of medical Cannabis sativa L. inflorescence and macerated oils based on HS-SPME coupled to GC–MS and LC-HRMS (q-Exactive Orbitrap) approach. J Pharm Biomed Anal 2018; 150: 208-219
• 16 Pacifici R, Marchei E, Salvatore F, Guandalini L, Busardò FP, Pichini S. Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry. Clin Chem Lab Med 2017; 55: 1555-1563
• 17 Schöffski K, Strohm D. Karl Fischer moisture determination. Encycl Anal Chem 2000; 1: 1-13
• 18 Dei Cas M, Casagni E, Saccardo A, Arnoldi S, Young C, Scotti S, Vieira de Manicor E, Gambaro V, Roda G. The Italian panorama of cannabis light preparation: Determination of cannabinoids by LC-UV. Forensic Sci Int 2020; 307: 110113