Cannabinoids for Behavioral Symptoms in Dementia: An Overview

 

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Abstract

Dementia, with loss of memory, cognitive abilities, and independent daily functioning, is increasing worldwide, related to an aging population. Currently, there is no curative treatment for dementia. Treatment of the frequently occurring behavioral and psychological symptoms of dementia (BPSD) is partially effective and associated with significant side effects.

Cannabinoids are lipophilic molecules acting on the CB1 end CB2 receptors, essential for main biological processes such as sleep, appetite, memory, and pain. Cannabinoids might have a positive impact on amyloid formation in Alzheimer’s disease, the main form of dementia, and on BPSD symptoms. Most knowledge currently concerns delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In the context of dementia and BPSD, THC might be beneficial for associated spasticity and possible pain or lack of appetite and CBD probably works better on sleep, agitation, and anxiety.

This overview of prospective clinical studies and randomized clinical trials, published between 2005 and April 2023, using cannabinoids for BPSD suggests that older studies using low-dose oral synthetic THC showed no positive results. Still, more recent studies using THC/CBD-based oral medication at higher doses show promising results and are feasible and safe in this elderly polymedicated population. Several RCTs are ongoing and planned worldwide, and we hope other trials will follow to establish clinical efficiency and optimal dosing, as well as other outcomes such as deprescribing other medications and facilitation of care. We suggest that researchers also address the more sociological aspects of prescribing cannabinoids for dementia and BPSD in their specific context.

Publication History

Received: 14 September 2023
Received: 29 December 2023

Accepted: 28 January 2024

Article published online:
06 March 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1 WHO fact sheet on dementia. 2023; https://www.who.int/news-room/fact-sheets/detail/dementia Accessed July 2023
  PubMed
• 2 NHS guidelines. https://www.nhs.uk/conditions/alzheimers-disease/ Accessed July 2023
  PubMed
• 3 Pautex S, Bianchi F, Daali Y. et al. Cannabinoids for behavioral symptoms in severe dementia: safety and feasibility in a long-term pilot observational study in nineteen patients. Front Aging Neurosci 2022; 14: 957665
  CrossrefPubMedGoogle Scholar
• 4 Aso E, Ferrer I. Cannabinoids for treatment of Alzheimer’s disease: Moving toward the clinic. Front Pharmacol 2014; 5: 37
  PubMedGoogle Scholar
• 5 Bahji A, Meyyappan AC, Hawken ER. Cannabinoids for the neuropsychiatric symptoms of dementia: A systematic review and meta-analysis. Can J Psychiatry 2020; 65: 365-376
  CrossrefPubMedGoogle Scholar
• 6 Broers B, Patà Z, Mina A. et al. Prescription of a THC/CBD-based medication to patients with dementia: A pilot study in Geneva. Med Cannabis Cannabinoids 2019; 2: 56-59
  CrossrefPubMedGoogle Scholar
• 7 Revol A. Prescription de cannabis à usage thérapeutique pour les personnes âgées atteintes de démence: L’engouement des proches aidants. Psychotropes 2019; 25: 129-149
  CrossrefPubMedGoogle Scholar
• 8 Bianchi F, Pautex S, Wampfler J. et al. Medical cannabinoids for painful symptoms in patients with severe dementia: A randomized, double-blind crossover placebo-controlled trial protocol. Front Pain Res 2023; 4: 1108832
  CrossrefPubMedGoogle Scholar
• 9 Whiting PF, Wolff RF, Deshpande S. et al. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA 2015; 313: 2456-2473
  CrossrefPubMedGoogle Scholar
• 10 Russo E, Guy GW. A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses 2006; 66: 234-246
  CrossrefPubMedGoogle Scholar
• 11 Mahlberg R, Walther S. Actigraphy in agitated patients with dementia. Monitoring treatment outcomes. Z Gerontol Geriatr 2007; 40: 178-184
  CrossrefPubMedGoogle Scholar
• 12 van den Elsen GAH, Ahmed AIA, Verkes RJ. et al. Tetrahydrocannabinol in behavioral disturbances in dementia: A crossover randomized controlled trial. Am J Geriatr Psychiatry 2015; 23: 1214-1224
  CrossrefPubMedGoogle Scholar
• 13 van den Elsen GA, Ahmed AI, Verkes RJ. et al. Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A randomized controlled trial. Neurology 2015; 84: 2338-2346
  CrossrefPubMedGoogle Scholar
• 14 Herrmann N, Ruthirakuhan M, Gallagher D. et al. Randomized placebo-controlled trial of nabilone for agitation in Alzheimer’s disease. Am J Geriatr Psychiatry 2019; 27: 1161-1173
  CrossrefPubMedGoogle Scholar
• 15 Hermush V, Ore L, Stern N. et al. Effects of rich cannabidiol oil on behavioral disturbances in patients with dementia: A placebo controlled randomized clinical trial. Front Med 2022; 9: 951889
  CrossrefPubMedGoogle Scholar
• 16 Walther S, Mahlberg R, Eichmann U. et al. Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology 2006; 185: 524-528
  CrossrefPubMedGoogle Scholar
• 17 Shelef A, Barak Y, Berger U. et al. Safety and efficacy of medical cannabis oil for behavioral and psychological symptoms of dementia: An-open label, add-on, pilot study. J Alzheimers Dis 2016; 51: 15-19
  CrossrefPubMedGoogle Scholar
• 18 McManus K, Ash E, Harper D. et al. Caring for behavioral symptoms of dementia (CBD): A new investigation into cannabidiol for the treatment of anxiety and agitation in Alzheimer’s dementia. Am J Geriatr Psychiatry 2021; 29: S110-S111
  CrossrefPubMedGoogle Scholar
• 19 Bartschi JG, Greenwood LM, Montgomery A. et al. Cannabidiol as a treatment for neurobiological, behavioral, and psychological symptoms in early-stage dementia: A double-blind, placebo-controlled clinical trial protocol. Cannabis Cannabinoid Res 2023; 8: 348-359
  PubMedGoogle Scholar
• 20 Cohen LM, Ash E, Outen JD. et al. Study rationale and baseline data for pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer’s dementia (THC-AD). Int Psychogeriatr 2021; 11: 1-6
  CrossrefPubMedGoogle Scholar
• 21 Scuteri D, Guida F, Boccella S. et al. NAbiximols Clinical Translation To the treatment of Pain and Agitation In Severe Dementia (NACTOPAISD): Clinical trial protocol. Biomed Pharmacother 2022; 153: 113488
  CrossrefPubMedGoogle Scholar
• 22 Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London and South London and Maudsley NHS STAND Trial. Exploring the feasibility of a cannabinoid oral spray for the treatment of behavioural symptoms in dementia in UK care homes. ISRCTN registry.
  PubMedGoogle Scholar
• 23 Timler A, Bulsara C, Bulsara M. et al. Use of cannabinoid-based medicine among older residential care recipients diagnosed with dementia: Study protocol for a double-blind randomised crossover trial. Trials 2020; 21: 188
  CrossrefPubMedGoogle Scholar
• 24 Eastern Virginia Medical School. Effects of THC-Free CBD Oil on Agitation in Patients With Alzheimer’s Disease; clinicaltrials.gov
  PubMed
• 25 Bianchi F, Pautex S, Wampfler J. et al. Preparation of a placebo-controlled trial of THC-CBD medication for severely demented patients with behavioral symptoms: A marathon full of barriers and pitfalls. Med Cannabis Cannabinoids 2022; 5: 159-198
  PubMedGoogle Scholar