Preclinical assessment of pharmacokinetics and anticonvulsant activity of CBDTech, a novel orally administered cannabidiol (CBD) formulation for seizure and epilepsy.

Abstract

Oral cannabidiol (CBD) product use is increasing despite suboptimal pharmacokinetics (PK) of currently available formulations. This study aimed to investigate the PK of CBD formulated using the drug delivery technology DehydraTECH™, which is hypothesized to increase absorption by bypassing first-pass liver metabolism due to enhanced lipophilic composition. Anticonvulsant activity of the leading formulation was investigated in the maximal electroshock seizure (MES) model. For the PK studies, Sprague Dawley rats were orally administered 25 mg/kg CBD in MCT oil or test formulations incorporating DehydraTECH™ (n = 10 per group). Plasma, brain tissue and urine and feces samples were collected to determine comparative absorption, distribution, and excretion by liquid chromatography with tandem mass spectrometry (LC-MS/MS). For the efficacy studies, a series of experiments was conducted using the lead formulation (CBDtech) from the PK trial. Effective dose (ED) of CBDtech in comparison to Epidiolex® (50-100 mg/kg), time of peak efficacy (TPE), and median ED (ED50) were assessed in the acute MES model. Clinical observations, presence/absence of hind limb extension (HLE), and maximum seizure severity (MSS) were recorded. No abnormal clinical signs were observed following dosing in any study. Area under the curve from dosing to the last measurable concentration (AUC_last) was 391 to 2708% improved following treatment with DehydraTECH™ formulations as compared with the MCT control (all p < 0.01). CBD was detected in brain, urine, and feces samples following all DehydraTECH™ treatments. Treatment with the ED of CBDtech (75 mg/kg) resulted in full protection (absence of HLE) in 66.6% of test subjects following MES test compared to 50% in the Epidiolex® group. The one-hour timepoint was determined to be the TPE for CBDtech; HLE was absent in 75% of animals and partial in 12.5% of animals. In comparison, in the Epidiolex® group HLE was absent in 50% of animals and partial in 12.5% of animals. The calculated ED50 was 75 mg/kg. Formulation of CBD with DehydraTECH™ resulted in improved bioavailability and efficacy in an acute seizure model. These findings contribute to a deeper understanding of CBD PK and will aid in the design of more effective CBD-based therapeutic interventions.