The Use of Cannabinoids in Treating Dementia

Dementia (K Marder, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Dementia

Abstract

Purpose of Review

To review and summarise the current evidence on the safety and efficacy of using cannabinoids to treat behavioural and neuropsychiatric symptoms of dementia.

Recent Findings

Two randomised controlled trials testing a synthetic form of tetrahydrocannabinol have shown that while well tolerated, there was no significant therapeutic effect, based on changes to scores on the neuropsychiatric inventory (NPI). Case reports and open label trials have indicated that there may be some therapeutic benefit of adding synthetic cannabinoids as an adjunctive therapy to reduce agitation, aberrant motor behaviour and nighttime behaviour.

Summary

More well-controlled clinical trials in older populations with varying severity of dementia are needed to evaluate the effectiveness of cannabinoids in treating behaviour symptoms of dementia. We provide suggestions for designing such trials and evaluating possible adverse effects of cannabinoids on cognitive and neuropsychiatric functioning.

Keywords

Cannabinoids Dementia Alzheimer’s disease Neuropsychiatric inventory Pharmacotherapies 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Eastwood R, Reisberg B. Mood and behaviour. In: Gauthier S, editor. Clinical diagnosis and management of Alzheimer’s disease. London: Martin Dunitz; 1996. p. 175–89.Google Scholar
  2. 2.
    Rojas-Fernandez CH, Lanctôt KL, Allen DD, MacKnight C. Pharmacotherapy of behavioral and psychological symptoms of dementia: time for a different paradigm? Pharmacotherapy. 2001;21(1):74–102.CrossRefPubMedGoogle Scholar
  3. 3.
    Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA. 2005;293(5):596–608.CrossRefPubMedGoogle Scholar
  4. 4.
    Ballard CG, Waite J, Birks J. Atypical antipsychotics for aggression and psychosis in Alzheimer’s disease. Cochrane Lib. 2006.Google Scholar
  5. 5.
    Lindsey PL. Psychotropic medication use among older adults: what all nurses need to know. J Gerontol Nurs. 2009;35(9):28–38.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    • Liu CS, Ruthirakuhan M, Chau SA, Herrmann N, Carvalho AF, Lanctot KL. Pharmacological management of agitation and aggression in Alzheimer’s disease: a review of current and novel treatments. Curr Alzheimer Res. 2016;13(10):1134–44. Reviews current pharmacological treatments for the management of Alzheimer’s disease, as well as updates on novel treatments. CrossRefPubMedGoogle Scholar
  7. 7.
    Maust DT, Bonar EE, Ilgen MA, Blow FC, Kales HC. Agitation in Alzheimer disease as a qualifying condition for medical marijuana in the United States. Am J Geriatr Psychiatry. 2016;24(11):1000–3.CrossRefPubMedGoogle Scholar
  8. 8.
    • Amanullah S, MacDougall K, Sweeney N, Coffin J, Cole J. Synthetic cannabinoids in dementia with agitation: case studies and literature review. Clin Neuropsychiatry. 2013;10(3-4):142–7. Case studies of patients who have benefitted from the addition of nabilone as an adjunctive treatment for agitation. Google Scholar
  9. 9.
    Benito C, Nunez E, Pazos MR, Tolon RM, Romero J. The endocannabinoid system and Alzheimer’s disease. Mol Neurobiol. 2007;36(1):75–81.CrossRefPubMedGoogle Scholar
  10. 10.
    Kogan NM, Mechoulam R. Cannabinoids in health and disease. Dialogues Clin Neurosci. 2007;9(4):413–30.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Iuvone T, Esposito G, De Filippis D, Scuderi C, Steardo L. Cannabidiol: a promising drug for neurodegenerative disorders? CNS Neurosci Ther. 2009;15(1):65–75.CrossRefPubMedGoogle Scholar
  12. 12.
    Beal JE, Olson R, Lefkowitz L, Laubenstein L, Bellman P, Yangco B, et al. Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. J Pain Symptom Manag. 1997;14(1):7–14.CrossRefGoogle Scholar
  13. 13.
    Haney M, Gunderson EW, Rabkin J, Hart CL, Vosburg SK, Comer SD, et al. Dronabinol and marijuana in HIV-positive marijuana smokers: caloric intake, mood, and sleep. J Acquir Immune Defic Syndr. 2007;45(5):545–54.CrossRefPubMedGoogle Scholar
  14. 14.
    Machado Rocha FC, Stefano S, De Cassia HR, Rosa Oliveira L, Da Silveira D. Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care. 2008;17(5):431–43.CrossRefGoogle Scholar
  15. 15.
    Sallan SE, Zinberg NE, Frei E III. Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med. 1975;293(16):795–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Ekert H, Waters K, Jurk I, Mobilia J, Loughnan P. Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol. Med J Aust. 1979;2(12):657–9.PubMedGoogle Scholar
  17. 17.
    Orr LE, McKernan JF, Bloome B. Antiemetic effect of tetrahydrocannabinol: compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis. Arch Intern Med. 1980;140(11):1431–3.CrossRefPubMedGoogle Scholar
  18. 18.
    Lutge EE, Gray A, Siegfried N. The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS. Cochrane Lib. 2013.Google Scholar
  19. 19.
    Bergamaschi MM, Queiroz RHC, Chagas MHN, De Oliveira DCG, De Martinis BS, Kapczinski F, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 2011;36(6):1219–26.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Zuardi AW, Crippa J, Hallak J, Pinto J, Chagas M, Rodrigues G, et al. Cannabidiol for the treatment of psychosis in Parkinson’s disease. J Psychopharmacol. 2009;23(8):979–83.CrossRefPubMedGoogle Scholar
  21. 21.
    Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Queensland Government. In: Health Do, editor. Clinical guidance for the use of medicinal cannabis products. Brisbane: Queensland Government; 2017. 32pp.Google Scholar
  23. 23.
    •• van den Elsen GA, Ahmed AI, Verkes R-J, Feuth T, van der Marck MA, Olde Rikkert MG. Tetrahydrocannabinol in behavioral disturbances in dementia: a crossover randomized controlled trial. Am J Geriatr Psychiatry. 2015;23(12):1214–24. One of two available RCTs testing the efficacy of THC in dementia; van den Elsen et al. found that there was no significant benefit of THC in reducing behavioural disturbance; however, the therapy was well tolerated with no significant adverse events. CrossRefPubMedGoogle Scholar
  24. 24.
    •• van den Elsen GA, Ahmed AI, Verkes R-J, Kramers C, Feuth T, Rosenberg PB, et al. Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: a randomized controlled trial. Neurology. 2015;84(23):2338–46. One of two available RCTs testing the efficacy of THC in dementia; van den Elsen et al. found that there was no significant benefit of THC in improving NPI scores; however, the therapy was well tolerated with no significant adverse events. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    • Walther S, Mahlberg R, Eichmann U, Kunz D. Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology (Berl). 2006;185(4):524–8. An open-label pilot study with six patients reported a reduction in nocturnal activity, as well as improvements in NPI scores, and no side effects were observed. CrossRefGoogle Scholar
  26. 26.
    • Shelef A, Barak Y, Berger U, Paleacu D, Tadger S, Plopsky I, 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(1):15–9. An open-label add-on study of 11 patients with Alzheimer’s disease reported the addition of cannabis oil was safely integrated, with significant benefits to CGI and NPI scores. CrossRefPubMedGoogle Scholar
  27. 27.
    Passmore MJ. The cannabinoid receptor agonist nabilone for the treatment of dementia-related agitation. Int J Geriatr Psychiatry. 2008;23(1):116–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Krishnan S, Cairns R, Howard R. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev. 2009;2Google Scholar
  29. 29.
    Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ (Online). 2015;350 (no pagination)(h369).Google Scholar
  30. 30.
    Douglas S, James I, Ballard C. Non-pharmacological interventions in dementia. Adv Psychiatr Treat. 2004;10(3):171–7.CrossRefGoogle Scholar
  31. 31.
    Panza F, Solfrizzi V, Seripa D, Imbimbo BP, Santamato A, Lozupone M, et al. Progresses in treating agitation: a major clinical challenge in Alzheimer’s disease. Expert Opin Pharmacother. 2015;16(17):2581–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Lonergan E, Luxenberg J, Colford JM, Birks J. Haloperidol for agitation in dementia. Cochrane Lib. 2002.Google Scholar
  33. 33.
    Gill SS, Bronskill SE, Normand S-LT, Anderson GM, Sykora K, Lam K, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007;146(11):775–86.CrossRefPubMedGoogle Scholar
  34. 34.
    Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005;294(15):1934–43.CrossRefPubMedGoogle Scholar
  35. 35.
    Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry. 2006;14(3):191–210.CrossRefPubMedGoogle Scholar
  36. 36.
    Seitz DP, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. The Cochrane Library. 2011.Google Scholar
  37. 37.
    Henry G, Williamson D, Tampi RR. Efficacy and tolerability of antidepressants in the treatment of behavioral and psychological symptoms of dementia, a literature review of evidence. Am J Alzheimers Dis Other Dement. 2011;26(3):169–83.CrossRefGoogle Scholar
  38. 38.
    Konovalov S, Muralee S, Tampi RR. Anticonvulsants for the treatment of behavioral and psychological symptoms of dementia: a literature review. Int Psychogeriatr. 2008;20(02):293–308.CrossRefPubMedGoogle Scholar
  39. 39.
    Kim Y, Wilkins KM, Tampi RR. Use of gabapentin in the treatment of behavioural and psychological symptoms of dementia. Drugs Aging. 2008;25(3):187–96.CrossRefPubMedGoogle Scholar
  40. 40.
    Tampi RR, Tampi DJ. Efficacy and tolerability of benzodiazepines for the treatment of behavioral and psychological symptoms of dementia: a systematic review of randomized controlled trials. Am J Alzheimers Dis Other Dement. 2014;29(7):565–74.CrossRefGoogle Scholar
  41. 41.
    Tanveer R, McGuinness N, Daniel S, Gowran A, Campbell VA. Cannabinoid receptors and neurodegenerative diseases. Wiley Interdiscip Rev Membr Transp Signal. 2012;1(5):633–9.CrossRefGoogle Scholar
  42. 42.
    van den Elsen GA, Ahmed AI, Lammers M, Kramers C, Verkes RJ, van der Marck MA, et al. Efficacy and safety of medical cannabinoids in older subjects: a systematic review. Ageing Res Rev. 2014;14:56–64.CrossRefPubMedGoogle Scholar
  43. 43.
    Andréasson S, Engström A, Allebeck P, Rydberg U. Cannabis and schizophrenia A longitudinal study of Swedish conscripts. Lancet. 1987;330(8574):1483–6.CrossRefGoogle Scholar
  44. 44.
    Zammit S, Allebeck P, Andreasson S, Lundberg I, Lewis G. Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ. 2002;325(7374):1199.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Morrison PD, Zois V, McKeown DA, Lee TD, Holt DW, Powell JF, et al. The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol Med. 2009;39(10):1607–16.CrossRefPubMedGoogle Scholar
  46. 46.
    Pope HG, Gruber AJ, Hudson JI, Cohane G, Huestis MA, Yurgelun-Todd D. Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug Alcohol Depend. 2003;69(3):303–10.CrossRefPubMedGoogle Scholar
  47. 47.
    Lyketsos CG, Garrett E, Liang K-Y, Anthony JC. Cannabis use and cognitive decline in persons under 65 years of age. Am J Epidemiol. 1999;149(9):794–800.CrossRefPubMedGoogle Scholar
  48. 48.
    Fernandez-Serrano MJ, Perez-Garcia M, Verdejo-Garcia A. What are the specific vs. generalized effects of drugs of abuse on neuropsychological performance? Neurosci Biobehav Rev. 2011;35(3):377–406.CrossRefPubMedGoogle Scholar
  49. 49.
    New South Wales Government. Palliative care Sydney, NSW2017 [Available from: https://www.medicinalcannabis.nsw.gov.au/clinical-trials/terminal-illness-trial#main-content.].

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.National Drug and Alcohol Research CentreThe University of New South WalesSydneyAustralia
  2. 2.The Centre for Youth Substance Abuse ResearchThe University of QueenslandBrisbaneAustralia
  3. 3.National Addiction Centre, Institute of Psychiatry, Psychology and NeuroscienceKings College LondonLondonUK

Personalised recommendations