A randomised, double-blind, placebo-controlled crossover trial on cannabinoid-based medication for behavioural disorders in old patients with severe dementia: the study results.

Background: Behavioural and psychological symptoms of dementia (BPSD) are frequent in patients with severe dementia and represent a major clinical challenge. Cannabinoid-based medications (CBM) have been proposed as a possible therapeutic option, but clinical evidence is still limited. Methods: We performed a multicenter, randomised, double-blind, placebo-controlled crossover trial in five long-term care facilities in Geneva, Switzerland. Patients with severe dementia received oral Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) oil (1:2 ratio, up to 20 mg/40 mg daily) and placebo in two 8-week periods separated by a 1-week washout. The primary outcome was agitation measured by the Cohen-Mansfield Agitation Inventory (CMAI). Secondary outcomes included behavioural scales, pain, as-needed psychotropic medication use and safety. Results: Twenty-five patients (average age 83 years) were randomised, and nineteen completed both study periods. No significant difference was observed between active treatment and placebo for the CMAI and other main behavioural outcomes. However, the use of pro re nata psychotropic medications was significantly lower during the active treatment period. The treatment was well tolerated, and no serious adverse events related to the study drug were observed. Conclusions: In this real-life crossover study, THC/CBD oil did not show superiority over placebo in reducing agitation in severe dementia. However, it was safe and associated with a significant reduction in the use of as-needed psychotropic medications prescribed for behavioural and psychological symptoms of dementia. CBM may represent a possible adjunctive option in selected patients, but further studies are needed.