Improved Bioavailability with Dry Powder Cannabidiol Inhalation: A Phase 1 Clinical Study

Area of Science:

• Pharmacology
• Drug Delivery Systems
• Cannabinoid Therapeutics

Background:

• Oral cannabidiol (CBD) formulations are FDA-approved for specific seizure disorders but face limitations.
• Extensive first-pass hepatic metabolism of oral CBD reduces its therapeutic efficacy and increases inactive metabolite levels.
• Inhalation offers a potential alternative route to bypass hepatic metabolism and improve systemic CBD delivery.

Purpose of the Study:

• To compare the pharmacokinetics (PK) of a novel dry-powder inhaler (DPI) CBD formulation against the oral solution Epidiolex® in healthy participants.
• To evaluate the safety and tolerability of inhaled CBD via a DPI compared to oral administration.

Main Methods:

• A Phase 1 clinical study involving healthy participants.
• Single-dose administration of DPI CBD (2.1 mg) and oral CBD (50 mg Epidiolex®).
• Pharmacokinetic analysis of CBD concentrations and time to maximum concentration (Tmax) in plasma.

Main Results:

• Inhaled DPI CBD achieved a 71-fold higher peak CBD concentration than oral Epidiolex®.
• The mean time to reach maximum CBD concentration was significantly faster with DPI CBD (3.8 min) versus oral CBD (122 min).
• DPI CBD administration resulted in a 24-fold lower dose compared to oral CBD for these outcomes.

Conclusions:

• Dry-powder inhaler CBD demonstrates significantly enhanced bioavailability and a more rapid onset of action compared to oral CBD formulations.
• The DPI CBD formulation is safe and well-tolerated, supporting its potential for treating acute conditions.
• Further research into DPI CBD is warranted for acute indications requiring rapid therapeutic effects.