A pilot double-blind placebo-controlled, randomized, safety, efficacy, and acceptability trial of a hemp-derived cannabidiol extract for the treatment of anxiety

Catalina Lopez-Quintero, PhD
University of Florida

Co-authors: Catalina Lopez-Quintero¹, Isabel Abril¹, Robyn Nelson¹, Lina M Velilla-Jimenez¹, Adaeze Anamege¹, Juan Perez-Carreno¹, Liva G LaMontagne¹, Carol Mathews^1
1University of Florida

Background and Study Aims: About a third of Americans will experience an anxiety disorder in their lifetime, and anxiety is the most common reason for using medical cannabis. However, evidence supporting its efficacy remains limited, and concerns about safety persist, underscoring the need for safer anxiolytics. Our pilot trial was designed to evaluate the safety, tolerability, and preliminary efficacy of a hemp derived CBD extract, a compound with a favorable safety profile and promising preliminary anxiolytic effects. The findings will inform larger clinical investigations of CBD as a potential adjunct to conventional antidepressants and benzodiazepines.

Study design: A double blind, placebo controlled, randomized pilot study (NCT06672666) examined the safety, tolerability, feasibility, and preliminary efficacy of a hemp derived cannabidiol (CBD) extract in adults with moderate to severe anxiety. Thirty participants (aged 18–55) were recruited from the Gainesville area and randomized to receive either CBD or placebo over a four week period that included a two week titration phase  (a titrated dosage ranging between 50 to 150 mg/day followed by a two week maintenance phase (maintenance dose of 150 mg/day). The protocol received approval from the UF Institutional Review Board and was conducted in accordance with federal regulations on cannabinoid products (IND 171489), ensuring the product contained < 0.3 % ∆⁹ THC. Standardized self report instruments (Hamilton Anxiety Rating Scale [HAM A] and Pittsburgh Sleep Quality Index [PSQI]) and laboratory safety measures (urine analysis, blood chemistry, liver enzymes) were collected at baseline and at each follow up visit. Adherence to and acceptability of the procedures were monitored regularly.

Results: Analyses will determine whether the CBD arm compared with placebo experienced a statistically significant reduction in HAM A scores and whether sleep quality improved as measured by the PSQI. None of the 30 participants have reported serious adverse events, or have laboratory results of concern, supporting tolerability of the 50–150 mg/day dose range. Feasibility metrics were encouraging: 26 of 29 participants (89 %) completed the study. The primary protocol deviations involved delays in scheduled evaluations, causing some visits to occur outside the proposed time window. Participants reported high acceptability of the study procedures.

Conclusions: These findings support the safety and acceptability of a four-week CBD regimen for anxiety and provide early evidence of dose safety. The data demonstrate that recruitment, retention, and data collection were feasible within a university setting, laying the groundwork for a larger phase II trial. The full dataset will be available for exploration, analyses, and discussion following study unblinding at the end of August.