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 its 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 three sequential cohorts (each with six active and two placebo subjects). Cohort 1 received 5 mg/kg CBD or placebo, cohort 2 received 10 mg/kg CBD or placebo (cohort 2), and cohort 3 received 20 mg/kg CBD or placebo. 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 postdose and plasma was analysed by liquid chromatography and mass spectrometry to assess the pharmacokinetics of the CBD formulation. RESULTS: CBD was well tolerated in the healthy volunteers (mean age: 24.0 years) treated with a single oral dose of CBD. There were no safety concerns with increasing the dose and the safety profiles of the CBD-treated and placebo-treated subjects were similar. The most frequently reported treatment emergent adverse events (TEAEs) were headache (17%) and diarrhoea (8%). There were no reported serious adverse events (SAEs) and no clinical laboratory findings, vital signs, ECGs or physical examination findings that were reported as TEAEs or were of clinical significance during the study. After a high-fat meal, CBD was detected in plasma samples at 15 min postdose; the median time to maximum plasma concentration (Tmax) was 4 h across all three CBD dose cohorts. The CBD plasma exposure [maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC)] 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 h, suggesting that 2-3 weeks are needed to fully eliminate CBD. CONCLUSIONS: This new CBD formulation demonstrated a favourable safety and tolerability profile in healthy volunteers that was consistent with the profiles reported for other purified CBD products. No severe or serious AEs were observed in this study and there were no safety concerns. TRIAL REGISTRATION: ACTRN12618001424291. Registered August 2018.