Medical cannabinoids for treatment of neuropsychiatric symptoms in dementia: systematic review

Introduction: Neuropsychiatric symptoms are an integral component of the natural history of dementia, occurring from prodromal to advanced stages of the disease process and leading to increased burden and morbidity. Clinical presentations are pleomorphic, and clinical management often requires combination of pharmacological and non-pharmacological interventions. However, limited efficacy and a non-negligible incidence of adverse events of psychotropic drugs reinforce the need for novel therapeutic options.

Aims: To review the evidence supporting the use of medical cannabinoids for the treatment of neuropsychiatric symptoms of dementia (NPS).

Methods: We conducted a systematic review of the medical literature to examine scientific publications reporting the use of medical cannabinoids for the treatment of NPS. Medical subject headings (MeSH) were used to search for relevant publications, and only papers disclosing original clinical information were included. A secondary search was performed within selected publications to account for relevant citations that were not retrieved by the systematic review. Selected papers were categorized according to the level of evidence generated by these studies on this clinical purpose, i.e. (1) controlled clinical trials; (2) open-label or observational studies; and (3) case reports.

Results: Fifteen publications with original clinical data were retrieved, being 5 controlled clinical trials, 3 open-label/observational studies, and 7 case reports. Most studies indicated that the use of medical cannabinoids engendered favorable outcomes for the treatment of neuropsychiatric symptoms related to moderate and advanced stages of dementia, particularly agitation, aggressive behavior and sleep and sexual disinhibition.

Conclusion: Medical cannabinoids represent a promising pharmacological approach for the treatment of NPS, with preliminary evidence of benefit at least in moderate to severe dementia. Controlled trials with longitudinal design and larger samples are required to examine the long-term efficacy of these drugs in different types and stages of dementia, in addition to their adverse events and risk of interactions with other drugs. Many pharmacological details are yet to be determined, such as dosing, treatment duration and concentrations of active compounds (e.g., CBD/THC ratio) in commercial preparations of medical cannabinoids.