Effects of a balanced cannabinoid extract on agitation and cognition in older adults with moderate Alzheimer's disease dementia: a randomized clinical trial protocol

Objectives: Alzheimer's disease (AD) is often associated with agitation, which negatively impacts patients' quality of life and increases the burden on caregivers. This protocol aims to investigate the effects of a balanced extract of Cannabis sativa, containing cannabidiol (CBD) and tetrahydrocannabinol (THC), on agitation and cognition in older adults with moderate-stage AD dementia. Methods: Randomized, controlled, prospective, open-label, parallel-group clinical trial lasting three months. A total of 124 participants aged 60 years or older, undergoing geriatric outpatient follow-up, will be included and allocated to two groups: a control group, which will receive the standard of care (SOC), and an intervention group, which will receive SOC plus a balanced extract of Cannabis sativa containing 300 mg CBD and 180 mg THC. The primary outcome will be reduction in agitation, assessed by the Cohen-Mansfield Agitation Inventory. Secondary outcomes include cognition (Addenbrooke's Mini-Cognitive Examination), neuropsychiatric symptoms (Neuropsychiatric Inventory), functionality (Functional Stage Scale and Pfeffer Functional Activities Questionnaire), and adverse events. Placebo control was ruled out for ethical reasons. The study will follow international ethical guidelines, with consent from participants’ legal proxies and supervision by an independent data monitoring committee. The protocol was approved by an ethics committee and registered with ReBEC. Expected results: A reduction in agitation is expected, with possible positive effects on cognition, neuropsychiatric symptoms, and functionality, while maintaining an acceptable safety profile. Relevance: This study may contribute to the use of cannabinoids as an adjunctive strategy in the management of behavioral symptoms of AD dementia in geriatric practice.