How to Better Deliver CBD

Cannabidiol (CBD) has tremendous therapeutic potential, but its development as an effective drug for the pharmaceutical industry is hampered by intrinsic properties such as low bioavailability, low aqueous solubility, and variable pharmacokinetic profiles.

Potential avenues to overcome these issues for CBD include self-emulsifying drug delivery systems, improved crystalline formulations, and other solid-state delivery formulations, most of which are in preclinical or early clinical development. This review identifies issues that affect the current delivery of solid-state CBD and how advanced drug development strategies can enable CBD to realize its full potential as a successful therapeutic agent.

Cannabidiol (CBD) is a phytocannabinoid used worldwide for a variety of indications, but with few approved medical uses. Purified CBD is approved only for the treatment of rare, refractory pediatric epilepsy [ 1, 2, 3, 4, 5 ]. Clinical trials are currently underway for potential indications such as anxiety, schizophrenia, addiction, post-traumatic stress disorder, graft-versus-host disease, cancer, and inflammatory bowel disease.

In order for it to be successfully used as a pharmaceutical, the inherent challenges to the effective administration of CBD must be identified and overcome, particularly via the oral route, which is the preferred route of administration by patients and drug developers. Some of the most notable issues with oral CBD include poor bioavailability, variable pharmacokinetic profiles, and possible polymorphism [ 6 ], which can have unintended consequences such as less predictable efficacy, increased side effects, and drug-drug interactions with increasing doses. This review will outline some of the current issues in CBD pharmaceutics, novel CBD formulations that are under development and clinical investigation, and strategies to improve CBD administration and efficacy.

References

1. Mitelpunkt, A.; Kramer, U.; Hausman Kedem, M.; Zilbershot Fink, E.; Orbach, R.; Chernuha, V.; Fattal-Valevski, A.; Deutsch, L.; Heffetz, D.; Sacks, H. The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study. Epilepsy Behav. 2019, 98, 233–237. [Google Scholar] [CrossRef] [PubMed]
2. Devinsky, O.; Patel, A.D.; Cross, J.H.; Villanueva, V.; Wirrell, E.C.; Privitera, M.; Greenwood, S.M.; Roberts, C.; Checketts, D.; VanLandingham, K.E.; et al. Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome. N. Engl. J. Med. 2018, 378, 1888–1897. [Google Scholar] [CrossRef] [PubMed] [Green Version]
3. Devinsky, O.; Marsh, E.; Friedman, D.; Thiele, E.; Laux, L.; Sullivan, J.; Miller, I.; Flamini, R.; Wilfong, A.; Filloux, F.; et al. Cannabidiol in patients with treatment-resistant epilepsy: An open-label interventional trial. Lancet Neurol. 2016, 15, 270–278. [Google Scholar] [CrossRef]
4. Thiele, E.A.; Marsh, E.D.; French, J.A.; Mazurkiewicz-Beldzinska, M.; Benbadis, S.R.; Joshi, C.; Lyons, P.D.; Taylor, A.; Roberts, C.; Sommerville, K.; et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018, 391, 1085–1096. [Google Scholar] [CrossRef]
5. Hess, E.J.; Moody, K.A.; Geffrey, A.L.; Pollack, S.F.; Skirvin, L.A.; Bruno, P.L.; Paolini, J.L.; Thiele, E.A. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia 2016, 57, 1617–1624. [Google Scholar] [CrossRef] [PubMed]
6. Mayr, T.; Grassl, T.; Korber, N.; Christoffel, V.; Bodensteiner, M. Cannabidiol revisited. IUCrData 2017, 2, x170276. [Google Scholar] [CrossRef] [Green Version]