title: Tetrahydrocannabinol in Behavioral Disturbances in Dementia: A Crossover Randomized Controlled Trial.
abstract: OBJECTIVE
  Neuropsychiatric symptoms (NPS) are highly prevalent in dementia, but effective pharmacotherapy without important side effects is lacking. This study aims to assess the efficacy and safety of oral tetrahydrocannabinol (THC) in the treatment of NPS in dementia.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, repeated crossover trial, consisting of six treatment blocks of 2 weeks each.
  
  
  METHODS
  Two hospital sites in The Netherlands, September 2011 to December 2013.
  
  
  METHODS
  Patients with dementia and clinically relevant NPS.
  
  
  METHODS
  Within each block THC (0.75 mg twice daily in blocks 1-3 and 1.5 mg twice daily in blocks 4-6) and placebo were administered in random order for 3 consecutive days, followed by a 4-day washout.
  
  
  METHODS
  Primary outcome was change in Neuropsychiatric Inventory (NPI) score. Analyses were performed intention-to-treat. Data from all subjects were used without imputation. Sample size required for a power of 80% was 20 patients, because of repeated crossover.
  
  
  RESULTS
  22 patients (15 men, mean age 76.4 [5.3] years) were included, of whom 20 (91%) completed the trial. THC did not reduce NPI compared to placebo (blocks 1-3: 1.8, 97.5% CI: -2.1 to 5.8; blocks 4-6: -2.8, 97.5% CI: -7.4 to 1.8). THC was well tolerated, as assessed by adverse event monitoring, vital signs, and mobility. The incidence of adverse events was similar between treatment groups. Four non-related serious adverse events occurred.
  
  
  CONCLUSIONS
  This is the largest randomized controlled trial studying the efficacy of THC for NPS, to date. Oral THC did not reduce NPS in dementia, but was well tolerated by these vulnerable patients, supporting future higher dosing studies.
authors.affiliation: Radboud Alzheimer Centre and Department of Geriatric Medicine, Radboud university medical center, Nijmegen, the Netherlands. Electronic address: Geke.vandenElsen@radboudumc.nl.
authors.forename: Geke A H
authors.initials: GAH
authors.lastname: van den Elsen
authors.affiliation: Radboud Alzheimer Centre and Department of Geriatric Medicine, Radboud university medical center, Nijmegen, the Netherlands; Department of Pharmacology and Toxicology, Radboud university medical center, Nijmegen, the Netherlands; Department of Elderly, Vincent van Gogh Institute, Venray, the Netherlands.
authors.forename: Amir I A
authors.initials: AIA
authors.lastname: Ahmed
authors.affiliation: Department of Psychiatry, Radboud university medical center, Nijmegen, the Netherlands.
authors.forename: Robbert-Jan
authors.initials: RJ
authors.lastname: Verkes
authors.affiliation: Department for Health Evidence, Radboud university medical center, Nijmegen, the Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: Feuth
authors.affiliation: Radboud Alzheimer Centre and Department of Geriatric Medicine, Radboud university medical center, Nijmegen, the Netherlands.
authors.forename: Marjolein A
authors.initials: MA
authors.lastname: van der Marck
authors.affiliation: Radboud Alzheimer Centre and Department of Geriatric Medicine, Radboud university medical center, Nijmegen, the Netherlands.
authors.forename: Marcel G M
authors.initials: MGM
authors.lastname: Olde Rikkert
mesh_terms: D000368:Aged; D018592:Cross-Over Studies; D003704:Dementia / Q000150:complications* / Q000523:psychology; D004311:Double-Blind Method; D013759:Dronabinol / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D009426:Netherlands; D011619:Psychotropic Drugs / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D011619:Psychotropic Drugs; D013759:Dronabinol
keywords: Dementia; neuropsychiatric symptoms; randomized controlled trial; tetrahydrocannabinol