Sativex (nabiximols) for the treatment of Agitation & Aggression in Alzheimer’s dementia in UK nursing homes: a randomised, double-blind, placebo-controlled feasibility trial

Abstract

Background: Alzheimer’s Disease (AD) patients often experience clinically significant agitation, leading to distress, increased healthcare costs and earlier institutionalisation. Current treatments have limited efficacy and significant side effects. Cannabinoid-based therapies, such as the nabiximols oral spray (Sativex®; 1:1 delta-9-tetrahydrocannabinol and cannabidiol), offer potential alternatives. We aimed to explore the feasibility and safety of nabiximols as a potential treatment for agitation in AD. Methods: The ‘Sativex® for Agitation & Aggression in Alzheimer’s Dementia’ (STAND) trial was a randomised, double-blind, placebo-controlled, feasibility study conducted in UK care homes. Participants with probable AD and predefined clinically significant agitation were randomised to receive placebo or nabiximols for 4 weeks on an up-titrated schedule, followed by a 4-week observation period. To be considered feasible, we prespecified the following thresholds that needed to be met: randomising 60 participants within 12 months, achieving a ≥ 75% follow-up rate at 4 weeks, maintaining ≥80% adherence to allocation and estimating a minimum effect size (Cohen’s d ≥ 0.3) on the Cohen–Mansfield Agitation Inventory. This trial is registered with ISRCTN 7163562. Findings: Between October 2021 and June 2022, 53 candidates were assessed; 29 met eligibility criteria and were randomised. No participants withdrew, and adherence was high (100%) and was generally feasible to deliver. The intervention was well tolerated (0 adverse reactions), with no safety concerns reported. Interpretation: Despite significant COVID-19 pandemic related challenges, administering nabiximols through oral mucosa to advanced AD patients with agitation demonstrated feasibility and safety. These findings support a larger confirmatory efficacy trial to evaluate the potential therapeutic efficacy of nabiximols for agitation in AD.