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

Topic: Risk, prevention and care in population studies

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 Δ9-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.

Key findings

• 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.
• 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.

Why it matters

In this small trial of 25 patients with severe dementia, a THC/CBD oil did not work better than placebo for agitation or other main behavioural outcomes. The treatment was well tolerated and was linked to less use of as-needed psychotropic medication, but the trial was small and the main outcomes were negative.

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Study details

• Study designRCT
• Participants25
• Effect sizeNo significant difference vs placebo on the CMAI (primary outcome); numeric estimate not reported in the abstract
• Evidence strengthNull-result

Limitations

Very small sample with 24% attrition; crossover design in a progressive illness; single city; effect sizes for the primary outcome are not reported in the abstract.

Read the original

• DOI: 10.1093/ageing/afag239
• PubMed: 42613673
• Original source →
• Free full text: PubMed Central →

Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).

@article{bianchi2026-42613673,
  author  = {Bianchi, Federica and Broers, Barbara and Desmeules, Jules Alexandre and Langlois, Angeline and Wampfler, James and Curtin, François and Pautex, Sophie},
  title   = {{A randomised, double-blind, placebo-controlled crossover trial on cannabinoid-based medication for behavioural disorders in old patients with severe dementia: the study results}},
  journal = {Age and ageing},
  year    = {2026},
  doi     = {10.1093/ageing/afag239},
  pmid    = {42613673},
  url     = {https://doi.org/10.1093/ageing/afag239}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• The Prevalence of Dementia: A Systematic Review and Meta-Analysis Journal of Alzheimer's disease : JAD · 2020-01-01 · usefulness score 70/100 · How common it is
• Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial JAMA neurology · 2023-12-01 · usefulness score 65/100 · Treatments
• The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia Neurology · 1994-12-01 · usefulness score 58/100 · Caregiving
• Palliative Care Resource Utilization in Patients with Prion Disease Alzheimer s & Dementia · 2025-12-01 · usefulness score 41/100 · End-of-life care

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