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

Cannabidiol (CBD), the primary non-psychoactive component of <i>Cannabis sativa</i>, has been gaining popularity as an analgesic in treatment of chronic painful conditions. Due to first-pass hepatic metabolism, oral CBD is considered to have low bioavailability. Our previous studies on 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 samples were collected for assessment of plasma concentrations, complete blood count (CBC), and biochemical analysis 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 were significant changes observed in CBC and biochemistry. The CBD peak plasma concentration (C_max) was 4.4-28.2 ng/mL, while its primary metabolite, 7-carboxy-CBD (7-COOH-CBD), was much higher (129-1,524 ng/mL), similar to those in reports of humans. The time to C_max and half-life of CBD were 0.25-21 and 5.1-24.2 days, respectively, and those in 7-COOH-CBD were 3-28 and 5.6-24.5 days, respectively. The concentration-time curves flattened with repeated injections. QoL improvement was observed for 4 weeks following injections. The results of this study offer clinically translatable information. Liposomal CBD injections every 6 weeks are practical, have no adverse effects, and provide long-term CBD and 7-COOH-CBD concentrations that approach steady-state concentrations over time. Additionally, liposomal CBD demonstrated remarkable efficacy in pain control and wellbeing improvement for several weeks and can potentially provide similar results in humans.