Tetrahydrocannabinol for neuropsychiatric symptoms in dementia

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 NPI total : 3.2, 95% confidence interval [CI] 23.6 to 10.0), nor were changes in scores for agitation (Cohen-Mansfield Agitation Inventory 4.6, 95% CI 23.0 to 12.2), quality of life (Quality of Life-Alzheimer's Disease 20.5, 95% CI 22.6 to 1.6), or activities of daily living (Barthel Index 0.6, 95% CI 20.8 to 1.9). The number of patients experiencing mild or moderate adverse events was similar (THC, n 5 16; placebo, n 5 14, p 5 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 welltolerated. Classification of evidence:This study provides Class I evidence that for patients with dementiarelated NPS, low-dose THC does not significantly reduce NPS at 21 days, though it is welltolerated. Neurology ® 2015;84:2338-2346 GLOSSARY AD 5 Alzheimer disease; AE 5 adverse event; CCGIC 5 Caregiver Clinical Global Impression of Change; CI 5 confidence interval; CMAI 5 Cohen-Mansfield Agitation Inventory; NPI 5 Neuropsychiatric Inventory; NPS 5 neuropsychiatric symptoms; PAL WMS-R 5 Paired Associate Learning Wechsler Memory Scale-Revised; QoL-AD 5 Quality of Life-Alzheimer's Disease Scale; RCT 5 randomized controlled trial; THC 5 D-9-tetrahydrocannabinol.

Medical Marijuana Use in Older Adults

“…15 There is little good-quality evidence studying the role of MM in depression specifically, although some trials investigating synthetic cannabinoids in pain assessed mood as a secondary outcome, and these did not suggest an effect on depression. 33,34 Nociceptive pain 22 Weak Neuropathic pain [17][18][19][20][21] Moderate Spasticity 23 Moderate Nausea and vomiting 9,15,29 Moderate Anorexia 9,30 Moderate Neurological and psychiatric illness 9,15,[31][32][33][34] Mixed (see text)…”

Agitation in Alzheimer Disease as a Qualifying Condition for Medical Marijuana in the United States

“…Thus far, the only randomized, placebo-controlled trial of cannabinoids for neuropsychiatric symptoms of dementia was negative (6), and overall there are far more indications for medical marijuana than there is evidence to support them (11). Currently, since medical marijuana for patients with dementia is specifically approved for agitation in patients with Alzheimer’s dementia, it is important to monitor two types of “indication creep”: first, whether use expands to other types of dementia; and second, whether it is used for other symptoms like anxiety, irritability, or wandering.…”

“…Several states include “agitation of Alzheimer’s dementia” as a qualifying condition for use of medical marijuana, despite extremely limited evidence for benefit from cannabinoids (5). The only randomized, placebo-controlled trial of marijuana for dementia (6), specifically tetrahydrocannabinol for dementia-related NPS, was negative, though the trial was small (50 patients), short-term (3 weeks), and used a relatively low-dose. A more recent study was positive, but open-label in design and even smaller (n=10 completers) (7).…”

Cannabinoids in the Older Person: A Literature Review

“…This found that although THC administration was well tolerated, it had no effect on neuropsychiatric symptoms when compared to the placebo. However, the authors did speculate that due to the tolerability of side effects, further work was required to assess the efficacy of higher doses [9].…”