De Caro C, Leo A, Citraro R, De Sarro C, Russo R, Calignano A, et al. The potential role of cannabinoids in epilepsy treatment. Expert Rev Neurother. 2017;17:1069–79.

Article  PubMed  Google Scholar 

Yau GTY, Tai W, Arnold JC, Chan HK, Kwok PCL. Cannabidiol for the treatment of brain disorders: Therapeutic potential and routes of administration. Pharm Res [Internet]. 2023; Available from: https://doi.org/10.1007/s11095-023-03469-1.

Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376:2011–20.

Article  CAS  PubMed  Google Scholar 

Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med. 2018;378:1888–97.

Article  CAS  PubMed  Google Scholar 

Iannone LF, Arena G, Battaglia D, Bisulli F, Bonanni P, Boni A, et al. Results from an Italian expanded access program on cannabidiol treatment in highly refractory Dravet syndrome and Lennox-Gastaut syndrome. Front Neurol. 2021;12:1–9.

Article  Google Scholar 

Iseger TA, Bossong MG. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr Res. 2015;162:153–61. Available from: https://doi.org/10.1016/j.schres.2015.01.033.

García-Gutiérrez MS, Navarrete F, Gasparyan A, Austrich-Olivares A, Sala F, Manzanares J. Cannabidiol: A potential new alternative for the treatment of anxiety, depression, and psychotic disorders. Biomolecules. 2020;10:1–34.

Article  Google Scholar 

Tomer S, Mu W, Suryawanshi G, Ng H, Wang L, Wennerberg W, et al. Cannabidiol modulates expression of type I IFN response genes and HIV infection in macrophages. Front Immunol. 2022;13:1–13.

Article  Google Scholar 

Lowe H, Toyang N, McLaughlin W. Potential of cannabidiol for the treatment of viral hepatitis. Pharmacognosy Res. 2017;9:116–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Salles ÉL, Khodadadi H, Jarrahi A, Ahluwalia M, Paffaro VA, Costigliola V, et al. Cannabidiol (CBD) modulation of apelin in acute respiratory distress syndrome. J Cell Mol Med. 2020;24:12869–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nguyen LC, Yang D, Nicolaescu V, Best TJ, Gula H, Saxena D, et al. Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses. Sci Adv. 2022;8.

Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psychotropic plant cannabinoids: New therapeutic opportunities from an ancient herb. Trends Pharmacol Sci. 2009;30:515–27.

Article  CAS  PubMed  Google Scholar 

Perucca E, Bialer M. Critical aspects affecting cannabidiol oral bioavailability and metabolic elimination, and related clinical implications. CNS Drugs. 2020;34:795–800. Available from: https://doi.org/10.1007/s40263-020-00741-5.

Contin M, Mohamed S, Santucci M, Lodi MAM, Russo E, Mecarelli O, et al. Cannabidiol in pharmacoresistant epilepsy: Clinical pharmacokinetic data from an expanded access program. Front Pharmacol. 2021;12:1–7.

Article  Google Scholar 

Millar SA, Stone NL, Yates AS, O’Sullivan SE. A systematic review on the pharmacokinetics of cannabidiol in humans. Front Pharmacol. 2018;9.

Lattanzi S, Zaccara G, Russo E, La Neve A, Lodi MAM, Striano P. Practical use of pharmaceutically purified oral cannabidiol in Dravet syndrome and Lennox-Gastaut syndrome. Expert Rev Neurother. 2021;21:99–110. Available from: https://doi.org/10.1080/14737175.2021.1834383.

Ramalho ÍM de M, Pereira DT, Galvão GBL, Freire DT, Amaral-Machado L, Alencar É do N, et al. Current trends on cannabidiol delivery systems: Where are we and where are we going? Expert Opin. Drug Deliv. Taylor and Francis Ltd. 2021;1577–87.

Reddy TS, Zomer R, Mantri N. Nanoformulations as a strategy to overcome the delivery limitations of cannabinoids. Phyther Res. 2023;1–13.

De Prá MAA, Vardanega R, Loss CG. Lipid-based formulations to increase cannabidiol bioavailability: In vitro digestion tests, pre-clinical assessment and clinical trial. Int J Pharm. 2021;609.

Kok LY, Bannigan P, Sanaee F, Evans JC, Dunne M, Regenold M, et al. Development and pharmacokinetic evaluation of a self-nanoemulsifying drug delivery system for the oral delivery of cannabidiol. Eur J Pharm Sci. 2022;168:106058. Available from: https://doi.org/10.1016/j.ejps.2021.106058.

Wang C, Dong C, Lu Y, Freeman K, Wang C, Guo M. Digestion behavior, in vitro and in vivo bioavailability of cannabidiol in emulsions stabilized by whey protein-maltodextrin conjugate: Impact of carrier oil. Colloids Surfaces B Biointerfaces. 2023;223:113154. Available from: https://doi.org/10.1016/j.colsurfb.2023.113154.

Izgelov D, Shmoeli E, Domb AJ, Hoffman A. The effect of medium chain and long chain triglycerides incorporated in self-nano emulsifying drug delivery systems on oral absorption of cannabinoids in rats. Int J Pharm. 2020;580:119201. Available from: https://doi.org/10.1016/j.ijpharm.2020.119201.

Cherniakov I, Izgelov D, Barasch D, Davidson E, Domb AJ, Hoffman A. Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration. J Control Release. 2017;266:1–7.

Article  CAS  PubMed  Google Scholar 

Itin C, Barasch D, Domb AJ, Hoffman A. Prolonged oral transmucosal delivery of highly lipophilic drug cannabidiol. Int J Pharm. 2020;581.

Crowley K, de Vries ST, Moreno-Sanz G. Self-reported effectiveness and safety of Trokie® Lozenges: A standardized formulation for the buccal delivery of cannabis extracts. Front Neurosci. 2018;12.

Huestis MA. Human cannabinoid pharmacokinetics. Chem. Biodivers. 2007. p. 1770–804.

d’Angelo I, Provenzano R, Florio E, Lombardi A, Trama U, Ungaro F, et al. Transmucosal delivery of the medical Cannabis oil via a nanoemulsion formulation. J Drug Deliv Sci Technol. 2023;79:104004. Available from: https://doi.org/10.1016/j.jddst.2022.104004.

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;128:201–9.

Article  CAS  PubMed  Google Scholar 

Roger K, Cabane B. Why are hydrophobic/water interfaces negatively charged? Angew Chemie - Int Ed. 2012;51:5625–8.

Article  CAS  Google Scholar 

Mason TG, Wilking JN, Meleson K, Chang CB, Graves SM. Nanoemulsions: formation, structure, and physical properties. J Phys Condens Matter. 2006;18:R635–66.

Article  CAS  Google Scholar 

Tonoyan L, Babu D, Reiz B, Le T, Siraki AG. Heating of consumer cannabis oils can lead to free radical initiated degradation, causing CBD and THC depletion. Free Radic Biol Med. 2022;192:77–83. Available from: https://doi.org/10.1016/j.freeradbiomed.2022.09.005.

Nakano Y, Tajima M, Sugiyama E, Sato VH, Sato H. Development of a novel nano-emulsion formulation to improve intestinal absorption of cannabidiol. Med Cannabis Cannabinoids. 2019;2:35–42.

Article  PubMed  PubMed Central  Google Scholar 

Hložek T, Uttl L, Kadeřábek L, Balíková M, Lhotková E, Horsley RR, et al. Pharmacokinetic and behavioural profile of THC, CBD, and THC+CBD combination after pulmonary, oral, and subcutaneous administration in rats and confirmation of conversion in vivo of CBD to THC. Eur Neuropsychopharmacol. 2017;27:1223–37.

Article  PubMed  Google Scholar 

della Rocca G, Paoletti F, Conti MB, Galarini R, Chiaradia E, Sforna M, et al. Pharmacokinetics of cannabidiol following single oral and oral transmucosal administration in dogs. Front Vet Sci. 2023;9.