Bioequivalence Assessment of Cannabidiol (CBD) Administrated in Oral Formulations
Condition: Pain
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The oral bio-availability of cannabidiol (CBD) is low due to poor water solubility and
      susceptibility to extensive first pass metabolism, resulting in relative bio-availability of
      6%.This project is designed to evaluate the plasma concentration vs. time profile of a self
      emulsifying drug delivery system termed Long Chain Nano Lipospheres (LNL) for enhancing the
      oral bio-availability of cannabidiol (CBD). The main goal of this study is to evaluate the
      bio-equivalence of CBD in the LNL product, compared to CBD in a sesame oil vehicle and CBD
      without any formulation, in powder form. Bio-equivalence is measured by AUC 0-24h, Tmax and
      Cmax.
    

Detailed description: 
      Cannabidiol (CBD) is considered the non-psychoactive component of the cannabis plant with a
      myriad of pharmacological attributes. There is preliminary data that CBD can be a useful
      treatment for different therapeutic conditions such as epilepsy, anxiety, pain etc. CBD has
      been investigated for its analgesic effect in patients with neuropathic and chronic pain,
      especially resistant to other treatments. Further supportive evidence for CBD's efficacy in
      treatment of pain, is established pre-clinically and requires additional research in a
      clinical setting. The use of CBD in epilepsy has been assimilated in treatment guidelines in
      many countries including Israel. However, the potential medical use of whole-plant cannabis
      extracts, particularly in children with a developing brain, is limited by the psychoactive
      properties and the adverse effects associated with long-term THC use.

      Although a therapeutic rational for the use of CBD has been demonstrated, an optimal oral
      dosage form to deliver this compound is not available yet. Oral administration is challenging
      because of CBD's poor solubility and extensive first pass metabolism, leading to an oral
      bioavailability of approximately 6%.

      In this project, investigators utilize a bio-pharmaceutical method to enhance the
      bioavailability of CBD using an advanced self-emulsifying drug delivery system termed Long
      Chain Nano Lipospheres (LNL). The LNL formulation is composed of long chain triglycerides,
      surfactants and co-solvent. This constellation is termed the pre-concentrate, which dissolves
      CBD in its lipid core and administered in a soft gelatin capsule. When reaching the aqueous
      phase of the GI tract, this pre-concentrate spontaneously forms a drug encapsulated O/W nano
      emulsion. Previously, investigators have shown in a pre-clinical investigation that
      incorporation of CBD into the LNL is a promising strategy to increase the compound's
      bioavailability.

      The primary goal of this study is to evaluate the bioequivalence of the developed CBD-LNL
      product to CBD in a sesame oil vehicle and CBD in powder form. Sesame oil is the commonly
      used vehicle for cannabinoids oral uptake for lack of other options. However, this option
      often leads to significant inter and intra subject variability in cannabinoids' plasma
      concentrations.

      The study will be performed on 12 healthy male volunteers. It will be randomized, blind,
      three way cross-over study intended to evaluate the pharmacokinetics of CBD. Each volunteer
      will receive CBD-LNL capsule, CBD in sesame oil vehicle capsule and CBD without any vehicle
      in powder form. All study groups will receive the same dose of CBD-90 mg. Blood samples will
      be drawn from forearm 30 minutes before (pre-dose) and every 30 minutes interval for the
      first 4 hours, then samples will be taken at 5,6,7,8,12 and 24 hours after the intake of the
      study drug. Blood concentration profiles of CBD and its main metabolites 7-hydroxy-CBD and
      CBD-glucoronide-11 will be determined in order to calculate the pharmacokinetic parameters of
      CBD.
    

Intervention name(s): CBD-sesame oil capsule; CBD-LNL capsule; CBD powder form capsule
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A capsule containing cannabidiol dissolved in sesame oil and surfactant vehicle.; A capsule containing Cannabidiol dissolved in self nano emulsifying formulation; Powder of Cannabidiol filled in a hard gelatin capsule, without formulation.
Other intervention name(s): Cannabidiol in sesame oil vehicle cpausle; Cannabidiol in Long Chain Nano Lipospheres formulation; Cannabidiol solid dosage form
Intervention MeSH terms: Cannabidiol
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: randomized blind, three way cross-over study
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Bioavailability; Pharmacokinetics