title: Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A randomized controlled trial.
abstract: OBJECTIVE
  To study the efficacy and safety of low-dose oral tetrahydrocannabinol (THC) in the treatment of dementia-related neuropsychiatric symptoms (NPS).
  
  
  METHODS
  This is a randomized, double-blind, placebo-controlled study. Patients with dementia and clinically relevant NPS were randomly assigned to receive THC 1.5 mg or matched placebo (1:1) 3 times daily for 3 weeks. Primary outcome was change in Neuropsychiatric Inventory (NPI), assessed at baseline and after 14 and 21 days. Analyses were based on intention-to-treat.
  
  
  RESULTS
  Twenty-four patients received THC and 26 received placebo. NPS were reduced during both treatment conditions. The difference in reduction from baseline between THC and placebo was not significant (mean difference NPItotal: 3.2, 95% confidence interval [CI] -3.6 to 10.0), nor were changes in scores for agitation (Cohen-Mansfield Agitation Inventory 4.6, 95% CI -3.0 to 12.2), quality of life (Quality of Life-Alzheimer's Disease -0.5, 95% CI -2.6 to 1.6), or activities of daily living (Barthel Index 0.6, 95% CI -0.8 to 1.9). The number of patients experiencing mild or moderate adverse events was similar (THC, n = 16; placebo, n = 14, p = 0.36). No effects on vital signs, weight, or episodic memory were observed.
  
  
  CONCLUSIONS
  Oral THC of 4.5 mg daily showed no benefit in NPS, but was well-tolerated, which adds valuable knowledge to the scarce evidence on THC in dementia. The benign adverse event profile of this dosage allows study of whether higher doses are efficacious and equally well-tolerated.
  
  
  METHODS
  This study provides Class I evidence that for patients with dementia-related NPS, low-dose THC does not significantly reduce NPS at 21 days, though it is well-tolerated.
authors.affiliation: From the Departments of Geriatric Medicine/Radboudumc Alzheimer Centre (G.A.H.v.d.E., A.I.A.A., M.A.v.d.M., M.G.M.O.R.), Pharmacology and Toxicology (A.I.A.A., C.K.), Psychiatry (R.-J.V.), Internal Medicine (C.K.), and Health Evidence (T.F.), Radboud university medical center, Nijmegen; the Department of Elderly (A.I.A.A.), Vincent van Gogh Institute, Venray; the Department of Clinical Pharmacy (C.K.), Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands; and the Department of Psychiatry and Behavioral Sciences (P.B.R.), John Hopkins University School of Medicine, Baltimore, MD. geke.vandenelsen@radboudumc.nl.
authors.forename: Geke A H
authors.initials: GA
authors.lastname: van den Elsen
authors.affiliation: From the Departments of Geriatric Medicine/Radboudumc Alzheimer Centre (G.A.H.v.d.E., A.I.A.A., M.A.v.d.M., M.G.M.O.R.), Pharmacology and Toxicology (A.I.A.A., C.K.), Psychiatry (R.-J.V.), Internal Medicine (C.K.), and Health Evidence (T.F.), Radboud university medical center, Nijmegen; the Department of Elderly (A.I.A.A.), Vincent van Gogh Institute, Venray; the Department of Clinical Pharmacy (C.K.), Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands; and the Department of Psychiatry and Behavioral Sciences (P.B.R.), John Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Amir I A
authors.initials: AI
authors.lastname: Ahmed
authors.affiliation: From the Departments of Geriatric Medicine/Radboudumc Alzheimer Centre (G.A.H.v.d.E., A.I.A.A., M.A.v.d.M., M.G.M.O.R.), Pharmacology and Toxicology (A.I.A.A., C.K.), Psychiatry (R.-J.V.), Internal Medicine (C.K.), and Health Evidence (T.F.), Radboud university medical center, Nijmegen; the Department of Elderly (A.I.A.A.), Vincent van Gogh Institute, Venray; the Department of Clinical Pharmacy (C.K.), Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands; and the Department of Psychiatry and Behavioral Sciences (P.B.R.), John Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Robbert-Jan
authors.initials: RJ
authors.lastname: Verkes
authors.affiliation: From the Departments of Geriatric Medicine/Radboudumc Alzheimer Centre (G.A.H.v.d.E., A.I.A.A., M.A.v.d.M., M.G.M.O.R.), Pharmacology and Toxicology (A.I.A.A., C.K.), Psychiatry (R.-J.V.), Internal Medicine (C.K.), and Health Evidence (T.F.), Radboud university medical center, Nijmegen; the Department of Elderly (A.I.A.A.), Vincent van Gogh Institute, Venray; the Department of Clinical Pharmacy (C.K.), Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands; and the Department of Psychiatry and Behavioral Sciences (P.B.R.), John Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Cees
authors.initials: C
authors.lastname: Kramers
authors.affiliation: From the Departments of Geriatric Medicine/Radboudumc Alzheimer Centre (G.A.H.v.d.E., A.I.A.A., M.A.v.d.M., M.G.M.O.R.), Pharmacology and Toxicology (A.I.A.A., C.K.), Psychiatry (R.-J.V.), Internal Medicine (C.K.), and Health Evidence (T.F.), Radboud university medical center, Nijmegen; the Department of Elderly (A.I.A.A.), Vincent van Gogh Institute, Venray; the Department of Clinical Pharmacy (C.K.), Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands; and the Department of Psychiatry and Behavioral Sciences (P.B.R.), John Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Ton
authors.initials: T
authors.lastname: Feuth
authors.affiliation: From the Departments of Geriatric Medicine/Radboudumc Alzheimer Centre (G.A.H.v.d.E., A.I.A.A., M.A.v.d.M., M.G.M.O.R.), Pharmacology and Toxicology (A.I.A.A., C.K.), Psychiatry (R.-J.V.), Internal Medicine (C.K.), and Health Evidence (T.F.), Radboud university medical center, Nijmegen; the Department of Elderly (A.I.A.A.), Vincent van Gogh Institute, Venray; the Department of Clinical Pharmacy (C.K.), Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands; and the Department of Psychiatry and Behavioral Sciences (P.B.R.), John Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rosenberg
authors.affiliation: From the Departments of Geriatric Medicine/Radboudumc Alzheimer Centre (G.A.H.v.d.E., A.I.A.A., M.A.v.d.M., M.G.M.O.R.), Pharmacology and Toxicology (A.I.A.A., C.K.), Psychiatry (R.-J.V.), Internal Medicine (C.K.), and Health Evidence (T.F.), Radboud university medical center, Nijmegen; the Department of Elderly (A.I.A.A.), Vincent van Gogh Institute, Venray; the Department of Clinical Pharmacy (C.K.), Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands; and the Department of Psychiatry and Behavioral Sciences (P.B.R.), John Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Marjolein A
authors.initials: MA
authors.lastname: van der Marck
authors.affiliation: From the Departments of Geriatric Medicine/Radboudumc Alzheimer Centre (G.A.H.v.d.E., A.I.A.A., M.A.v.d.M., M.G.M.O.R.), Pharmacology and Toxicology (A.I.A.A., C.K.), Psychiatry (R.-J.V.), Internal Medicine (C.K.), and Health Evidence (T.F.), Radboud university medical center, Nijmegen; the Department of Elderly (A.I.A.A.), Vincent van Gogh Institute, Venray; the Department of Clinical Pharmacy (C.K.), Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands; and the Department of Psychiatry and Behavioral Sciences (P.B.R.), John Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Marcel G M
authors.initials: MG
authors.lastname: Olde Rikkert
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003704:Dementia / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000209:etiology; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D063386:Cannabinoid Receptor Agonists; D013759:Dronabinol