There are currently no safe and effective approved medications for behavioral and psychological symptoms of dementia (BPSD). Cannabidiol (CBD), a non-intoxicating cannabinoid, with anti-anxiety and anti-psychotic properties shows promise (Bhattacharyya et al., Reference Bhattacharyya, Wilson, Appiah-Kusi, O’Neill, Brammer, Perez, Murray, Allen, Bossong and McGuire2018; McGuire et al., Reference McGuire, Robson, Cubala, Vasile, Morrison, Barron, Taylor and Wright2018; O’Neill et al., Reference O’Neill, Wilson, Blest-Hopley, Annibale, Colizzi, Brammer, Giampietro and Bhattacharyya2020), with evidence of good tolerability and acceptability of formulations containing CBD alone, as opposed to those containing delta-9-tetrahydrocannabinol, a cannabinoid with psychotomimetic effects (Velayudhan et al., Reference Velayudhan, McGoohan and Bhattacharyya2021a; Velayudhan et al., Reference Velayudhan, McGoohan and Bhattacharyya2021b).
To evaluate the feasibility and obtain preliminary evidence in support of a future fully powered efficacy trial of CBD, we carried out a phase 2a, single-site, parallel-group, double-blind, placebo-controlled, randomized trial in patients with Alzheimer’s disease (AD) and BPSD (EudraCT Number – 2019-002106-52). Participants of either sex aged 55 years or older with possible or probable AD (McKhann et al., Reference McKhann, Drachman, Folstein, Katzman, Price and Stadlan1984) were eligible, if they had BPSD with total score on Neuropsychiatric Inventory (NPI) (Cummings, Reference Cummings1997) ≥4 and at least 1 item with score of 2 or more (frequency × severity) on one of the domains of anxiety, agitation, hallucinations, or delusions. The primary endpoints were acceptability, adherence to treatment, and retention rates from baseline to week 6, while secondary outcomes included safety/tolerability and clinical and cognitive measures (more details in Supplementary Methods). Ethical approval was obtained from the NHS Health Research Authority (20/EE/0014) and regulatory approval from the Medicines and Healthcare products Regulatory Agency, UK. Written informed consent from participants or their legally authorized representative was obtained.