Examining the Systemic Bioavailability of Cannabidiol and Tetrahydrocannabinol from a Novel Transdermal Delivery System in Healthy Adults: A Single-Arm, Open-Label, Exploratory Study.

INTRODUCTION

Transdermal cannabinoids may provide better safety and bioavailability profiles compared with other routes of administration. This single-arm, open-label study investigated a novel topical transdermal delivery system on the pharmacokinetics of cannabidiol (CBD) and tetrahydrocannabinol (THC).

METHODS

Participants were 39.5 ± 7.37 years old and healthy, based on a review by the Medical Director. Blood was collected pre-dose and 10, 20, 30, and 45 min, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h after topical application of 100 mg CBD:100 mg THC. Psychoactive effects were assessed prior to each timepoint. Area-under-the-curve (AUC), maximum concentration (C), time to maximum concentration (T), area-under-the-curve to infinity (AUC), terminal elimination rate constant (λ), terminal half-life (t½), and absorption rate constant (k) were measured individually for CBD and THC. Safety was assessed by clinical chemistry, hematology, and adverse events.

RESULTS

AUC for CBD and THC was 3329.8 ± 3252.1 and 2093.4 ± 2090.6 pg/mL/h, with C of 576.52 ± 1016.18 and 346.57 ± 776.85 pg/mL, respectively. T for CBD and THC was 8 h, ranging from 2.5 h to 12 h and 10 min to 12 h, respectively. AUC for CBD and THC was 6609.2 ± 7056.4 and 3721.0 ± 3251.7 pg/mL/h, with t of 5.68 ± 1.5 and 5.38 ± 1.25 h, respectively. CBD was absorbed at a faster rate compared with THC (123.36 ± 530.97 versus 71.5 ± 1142.19 h) but with similar λ (0.12 ± 0.029 versus 0.13 ± 0.03 h). No psychoactive effects were reported. Transdermal cannabinoid delivery was safe and well tolerated in the population studied.

CONCLUSION

To our knowledge, this is the first pharmacokinetic study in humans that demonstrated CBD and THC entering systemic circulation via transdermal administration . This study represents an important contribution to understanding the pharmacokinetics of transdermal cannabinoids.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov Identifier-NCT05121506 (November 16, 2021).