Abstracts

Rationale: Cannabis sativa contains more than a hundred phytocannabinoid compounds, including cannabidiol (CBD), a non-psychotomimetic compound. CBD is of significant interest due to its anti-inflammatory, anti-oxidative and anti-necrotic protective effects positioning it a novel and promising therapeutic candidate in epilepsy, ophthalmology, cardiovascular disease, neurodegenerative disease, cancer, addiction, and other indications. However, current orally-directed CBD therapeutics have significant challenges as a result of poor bioavailability, short half-life, and liver toxicity concerns. The aim of this study was to explore the pharmacokinetics of CBD delivered via 24-hour subcutaneous infusion. Subcutaneous infusion avoids the first pass effect, potentially providing an effective alternative route of administration for drugs with oral delivery challenges. Methods: We investigated the pharmacokinetics (PK) of CBD delivered over a single 24-hour period using the h-Patch™ subcutaneous infusion device in dogs.  The h-Patch™ technology is already marketed via an FDA approved for insulin delivery (V-Go device, Valeritas, Inc). Two CBD dosage regimens (40mg/24h and 76mg/24h) were tested with PK evaluated at timepoints out to 48h from the start of infusion (24h after completion of CBD delivery). Results: Both dosages displayed rapid absorption and distribution with CBD levels in blood detected within an hour of the beginning of infusion, followed by prolonged elimination with CBD still detectable 24h after completion of h-Patch™ infusion (Figure 1). We find our peak dose normalized CBD plasma levels (Figure 2) on par with published human dose normalized plasma concentrations from oral administration of 300mg CBD (Birnbaum AK, et al. Epilepsia 2019 Aug 60(8): 1586-1592). Conclusions: To our knowledge this is the first report of subcutaneous infusion of CBD, and is particularly encouraging given the kinetics of absorption & distribution, plasma level of drug detected, and prolonged near steady state levels well after completion of a single 24h infusion. The h-Patch™ provides a simple all-in-one delivery device with no exposed needle, no programming or infusion set required. Over 20 million h-Patch devices have been sold to consumers for easy to use, convenient, and discreet delivery of insulin (V-Go device, Valeritas, Inc). This same technology can be applied to daily subcutaneous infusion of CBD providing several distinct advantages including elimination of toxic metabolites produced by liver metabolism, minimization of the impact of variation in CBD metabolism in the general population, dramatic improvement of half life, and superior bioavailability along with the ability to dramatically lower the overall amount of drug needed to achieve therapeutic levels. These features contribute to a dramatically improved risk-reward profile for a CBD isolate therapeutic and open the door to reliable, uniform dosing providing practitioners and patients an additional level of comfort and peace of mind. Funding: Funding for this study was provided by Valeritas, Inc.