Regular Research Article
Tetrahydrocannabinol in Behavioral Disturbances in Dementia: A Crossover Randomized Controlled Trial

https://doi.org/10.1016/j.jagp.2015.07.011Get rights and content

Objectives

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.

Design

Randomized, double-blind, placebo-controlled, repeated crossover trial, consisting of six treatment blocks of 2 weeks each.

Setting

Two hospital sites in The Netherlands, September 2011 to December 2013.

Participants

Patients with dementia and clinically relevant NPS.

Intervention

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.

Measurements

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.

Section snippets

Study Design

This was a multicenter, phase II, repeated crossover, randomized, double-blind, placebo-controlled trial, conducted in accordance with the Declaration of Helsinki, Good Clinical Practice, and International conference on Harmonization guidelines and registered at www.clinicaltrials.org (NCT01302340). The study took place at the Alzheimer Centre of the Radboud University Medical Center (Radboud UMC, Nijmegen, The Netherlands) and the Vincent van Gogh Institute (Venray, The Netherlands), between

Conclusions

In the present study, we found no benefit of THC treatment (0.75 mg and 1.5 mg, twice daily) on NPS in dementia on either of the outcome measures. Although THC failed to improve NPS, intermittent treatment demonstrated safety in older dementia patients. Previous studies all showed positive effects of THC (2.5 to 7.0 mg, daily) on behavioral and nighttime disturbances,13, 14, 34, 35 although two of these studies were randomized controlled trials with a small number of patients (N = 2; N = 15),14

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