Liposomal-synthetic-cannabidiol: Preliminary translational evidence of efficacy, tolerability and pharmacokinetics following repeated subcutaneous injections in two goats

Yael Shilo-Benjamini^1,2*Wiessam Abu Ahmad³Dinorah Barasch⁴Eran Lavy¹Daniel Zilbersheid²Yechezkel Barenholz²Ahuva Cern²

• ¹Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, Jerusalem, Israel
• ²Laboratory of Membrane and Liposome Research, Department of Biochemistry, Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem, Israel
• ³Hadassah University Medical Center, Jerusalem, Israel
• ⁴The Mass Spectrometry Unit, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel

Cannabidiol (CBD), the primary non-psychoactive component of Cannabis sativa, is gaining popularity as an analgesic in chronic painful conditions. Due to first-pass hepatic metabolism, bioavailability of oral CBD is considered low. Our previous results in dogs indicate that synthetic CBD encapsulation in liposomes facilitates controlled-drug-release and provides long-term CBD plasma concentrations. In the present study, liposomal-CBD (5 mg/kg) was repeatedly injected subcutaneously in two goats, due to suspected pain and deterioration in quality of life (QoL). Blood was sampled for plasma concentrations, complete blood count (CBC) and biochemistry before and up to 6-weeks after each injection. Efficacy was assessed by the caregivers via QoL weekly scoring, and adverse effects were monitored. A total of 14 injections were administered. No adverse effects were recorded, nor significant changes in CBC and biochemistry. CBD peak plasma concentration (Cmax) was 4.4–28.2 ng/mL, while its primary metabolite, 7-carboxy-CBD, was much higher 129–1,524 ng/mL, similar to reports in people. Time to Cmax and half-life were 0.25–21 and 5.1–24.2 days (CBD), and 3– 28 and 5.6–24.5 days (7-carboxy-CBD), respectively. The concentration-time curves flattened with repeated injections. QoL improvement was observed for 4-weeks following injections. The results of this study offer a clinically translatable information. Liposomal-CBD injections every-6-weeks are practical, have no adverse effects, and provide long-term CBD and 7-carboxy-CBD concentrations, which approached steady-state over time. Additionally, liposomal-CBD demonstrated remarkable efficacy in pain control and wellbeing improvement for several weeks, and can potentially provide similar results in people.