A Systematic Review of Clinical Studies on the Effect of Psychoactive Cannabinoids in Psychiatric Conditions in Alzheimer Dementia.

Background: The systematic reviews and meta-analyses performed until now did not provide the adequate picture of actual knowledge in the field of neuropsychiatric symptoms treatment using psychotropic cannabinoids in patients with Alzheimer disease (AD). The Study Question: Which is the level of evidence, from quantitative and qualitative point of view, concerning the efficacy and safety of the treatment with psychotropic cannabinoids of neuropsychiatric symptoms in AD? Study Design: PubMed, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar Data, and Clinicaltrials.gov were searched for randomized clinical trials with cannabinoids in Alzheimer dementia agitation and aggression. Measures And Outcomes: The rationale, the objectives, and the methods used for searching the trials have been established according to PRISMA Criteria 2009. Results: The total number of patients in the 9 publications evaluated in this study, which included data from 6 clinical trials, was 422 patients-treatments, where treatment was a psychoactive cannabinoid or placebo, some of them obtained by multiplying selected patients with the number of cannabinoid treatments in the crossover studies. There are multiple sources of bias in the analyzed studies; 2 elements have prevented conclusive results. One element was polypragmazia, a major role being played by the use of psychotropic drugs other than cannabinoids, in an effort to reduce agitation and aggressive behavior. The second one was the large number of concomitant symptoms, for example, pain (commonly causing anxiety and agitation). Conclusions: No clear conclusion can be drawn on the effectiveness of psychoactive cannabinoids in the treatment of psychiatric manifestations, in particular agitation and aggression, in AD. In the future, large randomized controlled trial with adequate designs, without crossover and for longer duration, adapted to cannabinoid pharmacokinetics, is required to establish the real efficacy and safety of these drugs in aggressive and/or agitated patients with AD.