A Phase 1, Randomised, Placebo-controlled, Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of Cannabidiol in Fed Healthy Volunteers

Abstract

Background There is increasing interest in the use of purified cannabidiol (CBD) as a treatment for a wide range of conditions, due to reported anti-inflammatory, anxiolytic, antiemetic and anticonvulsant properties. Objective The objective of this study was to assess the safety, tolerability, and pharmacokinetics of a single ascending dose of a new lipid-based oral formulation of CBD in healthy volunteers after a high fat meal.

Methods A total of 24 eligible healthy volunteers (aged 18 – 48 years) were randomised to one of 3 sequential cohorts (each with 6 active + 2 placebo subjects) to receive 5 mg/kg CBD or placebo (cohort 1), 10 mg/kg CBD or placebo (cohort 2) or 20 mg/kg CBD or placebo (cohort 3). Data relating to adverse events, vital signs, clinical laboratory assessments, 12-lead ECGs, physical examinations and concomitant medications were collected to assess safety and tolerability. Blood samples were collected up to 8 days post-dose and plasma analysed by liquid chromatography and mass spectrometry to assess the pharmacokinetics of the CBD formulation.

Results CBD was well tolerated in healthy volunteers (mean age, 24.0 years) treated with a single oral dose of CBD. There were no safety concerns with increasing dose and the safety profile was similar between the CBD and placebo-treated subjects. The most frequent reported treatment-emergent adverse events (TEAEs) were headache (17%) and diarrhoea (8%). There were no reported serious adverse events (SAEs), or any clinical laboratory findings, vital signs, ECG, or physical examination findings reported as TEAEs or of clinical significance during the study. There were no safety concerns with increasing dose. After a high fat meal, CBD was detected in subject plasma samples 15 minutes post-dose, with a median time to maximum plasma concentration (Tmax) of 4 hours across all 3 CBD dose cohorts. The CBD plasma exposure [maximum observed plasma concentration (Cmax), area under the concentration-time curve (AUC) values] increased in a dose proportional manner and declined to levels approaching the lower level of quantification by Day 8. The terminal elimination half-life was approximately 70 hours, suggesting that CBD would require 2-3 weeks to be fully eliminated.

Conclusions This new CBD formulation demonstrated a favourable safety and tolerability profile in healthy volunteers, consistent with that reported for other purified CBD products. No severe or serious AEs were observed in this study and there were no safety concerns.