Cannabinoids for the treatment of agitation and aggression in Alzheimer's disease

CNS Drugs

Volumn 29, Issue 8, 2015, Pages 615-623

  Liu, Celina S ^a,b   Chau, Sarah A ^a,b   Ruthirakuhan, Myuri ^b   Lanctôt, Krista L ^a,b   Herrmann, Nathan ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b SUNNYBROOK RESEARCH INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; CANNABINOID; NABILONE; NEUROTRANSMITTER; PLACEBO; TAU PROTEIN; ENDOCANNABINOID;

AGGRESSION; AGITATION; ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BEHAVIOR DISORDER; DATA BASE; DRUG EFFICACY; DRUG SAFETY; HUMAN; MEDICAL LITERATURE; NEUROPSYCHIATRY; NONHUMAN; PAIN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); SYSTEMATIC REVIEW; TREATMENT OUTCOME; ANIMAL; DRUG EFFECTS; METABOLISM; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PSYCHOMOTOR AGITATION;

AGGRESSION; ALZHEIMER DISEASE; ANIMALS; CANNABINOIDS; ENDOCANNABINOIDS; HUMANS; OXIDATIVE STRESS; PSYCHOMOTOR AGITATION;

EID: 84942982408     PISSN: 11727047     EISSN: 11791934     Source Type: Journal    
DOI: 10.1007/s40263-015-0270-y     Document Type: Article

References (97)

1. Wortmann M. Dementia: a global health priority - highlights from an ADI and World Health Organization report. Alzheimers Res Ther. 2012;4(5):40.
2. Garcia-Alberca JM, et al. Prevalence and comorbidity of neuropsychiatric symptoms in Alzheimer's disease. Actas Esp Psiquiatr. 2008;36(5):265-70.
3. Lyketsos CG. Neuropsychiatric symptoms (behavioral and psychological symptoms of dementia) and the development of dementia treatments. Int Psychogeriatr. 2007;19(3):409-20.
4. Banerjee S, et al. Quality of life in dementia: more than just cognition. An analysis of associations with quality of life in dementia. J Neurol Neurosurg Psychiatry. 2006;77(2):146-8.
5. Cohen-Mansfield J, Libin A, Marx MS. Nonpharmacological treatment of agitation: a controlled trial of systematic individualized intervention. J Gerontol A Biol Sci Med Sci. 2007;62(8):908-16.
6. Cohen-Mansfield J, Werner P. Management of verbally disruptive behaviors in nursing home residents. J Gerontol A Biol Sci Med Sci. 1997;52(6):M369-77.
7. Ballard CG, et al. Management of agitation and aggression associated with Alzheimer disease. Nat Rev Neurol. 2009;5(5):245-55.
8. Ballard C, et al. Management of agitation and aggression associated with Alzheimer's disease: controversies and possible solutions. Curr Opin Psychiatry. 2009;22(6):532-40.
9. Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease. Cochrane Database Syst Rev. 2006;1:Cd003476.
10. Schneider LS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006;355(15):1525-38.
11. Herrmann N, Lanctot KL, Hogan DB. Pharmacological recommendations for the symptomatic treatment of dementia: the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012. Alzheimers Res Ther. 2013;5((Suppl 1)):S5.
12. Bedse G, et al. The role of endocannabinoid signaling in the molecular mechanisms of neurodegeneration in Alzheimer's disease. J Alzheimers Dis. 2015;43(4):1115-36.
13. Rossi S, Motta C, Musella A, Centonze D. The interplay between inflammatory cytokines and the endocannabinoid system in the regulation of synaptic transmission. Neuropharmacology. 2015;96((Pt A)):105-12.
14. Sanchez AJ, Garcia-Merino A. Neuroprotective agents: cannabinoids. Clin Immunol. 2012;142(1):57-67.
15. Scotter EL, Abood ME, Glass M. The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br J Pharmacol. 2010;160(3):480-98.
16. Glass M, Dragunow M, Faull RL. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience. 1997;77(2):299-318.
17. Mackie K. Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb Exp Pharmacol. 2005;168:299-325.
18. Kathmann M, Bauer U, Schlicker E. CB1 receptor density and CB1 receptor-mediated functional effects in rat hippocampus are decreased by an intracerebroventricularly administered antisense oligodeoxynucleotide. Naunyn Schmiedebergs Arch Pharmacol. 1999;360(4):421-7.
19. Karkkaine E, Tanila H, Laitinen JT. Functional autoradiography shows unaltered cannabinoid CB1 receptor signalling in hippocampus and cortex of APP/PS1 transgenic mice. CNS Neurol Disord Drug Targets. 2012;11(8):1038-44.
20. Rapp PR, Heindel WC. Memory systems in normal and pathological aging. Curr Opin Neurol. 1994;7(4):294-8.
21. Mann DM. The pathogenesis and progression of the pathological changes of Alzheimer's disease. Ann Med. 1989;21(2):133-6.
22. Moise AM, et al. An endocannabinoid signaling system modulates anxiety-like behavior in male Syrian hamsters. Psychopharmacology. 2008;200(3):333-46.
23. Martin M, et al. Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology. 2002;159(4):379-87.
24. Klegeris A, Bissonnette CJ, McGeer PL. Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor. Br J Pharmacol. 2003;139(4):775-86.
25. Sheng WS, et al. Synthetic cannabinoid WIN55,212-2 inhibits generation of inflammatory mediators by IL-1beta-stimulated human astrocytes. Glia. 2005;49(2):211-9.
26. Tolon RM, et al. The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages. Brain Res. 2009;1283:148-54.
27. Vilela FC, Giusti-Paiva A. Cannabinoid receptor agonist disrupts behavioral and neuroendocrine responses during lactation. Behav Brain Res. 2014;263:190-7.
28. Rodriguez-Arias M, et al. CB1 cannabinoid receptor-mediated aggressive behavior. Neuropharmacology. 2013;75:172-80.
29. Lanctot KL, Herrmann N, Mazzotta P. Role of serotonin in the behavioral and psychological symptoms of dementia. J Neuropsychiatry Clin Neurosci. 2001;13(1):5-21.
30. Lanctot KL, et al. GABAergic function in Alzheimer's disease: evidence for dysfunction and potential as a therapeutic target for the treatment of behavioural and psychological symptoms of dementia. Can J Psychiatry. 2004;49(7):439-53.
31. Tanaka Y, et al. Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease. Ann Nucl Med. 2003;17(7):567-73.
32. Pinto T, Lanctot KL, Herrmann N. Revisiting the cholinergic hypothesis of behavioral and psychological symptoms in dementia of the Alzheimer's type. Ageing Res Rev. 2011;10(4):404-12.
33. Chami L, Checler F. BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and beta-amyloid production in Alzheimer's disease. Mol Neurodegener. 2012;7:52.
34. Aso E, et al. CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AbetaPP/PS1 mice. J Alzheimers Dis. 2013;35(4):847-58.
35. Esposito G, et al. The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells. J Mol Med (Berl). 2006;84(3):253-8.
36. Volicer L, et al. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 1997;12(9):913-9.
37. Walther S, et al. Randomized, controlled crossover trial of dronabinol, 2.5 mg, for agitation in 2 patients with dementia. J Clin Psychopharmacol. 2011;31(2):256-8.
38. Mahlberg R, Walther S. Actigraphy in agitated patients with dementia. Monitoring treatment outcomes. Z Gerontol Geriatr. 2007;40(3):178-84.
39. Walther S, et al. Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology. 2006;185(4):524-8.
40. Woodward MR, et al. Dronabinol for the treatment of agitation and aggressive behavior in acutely hospitalized severely demented patients with noncognitive behavioral symptoms. Am J Geriatr Psychiatry. 2014;22(4):415-9.
41. Passmore MJ. The cannabinoid receptor agonist nabilone for the treatment of dementia-related agitation. Int J Geriatr Psychiatry. 2008;23(1):116-7.
42. Cheer JF, et al. Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. J Neurosci. 2004;24(18):4393-400.
43. Pistis M, et al. Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biol Psychiatry. 2004;56(2):86-94.
44. Kirilly E, Hunyady L, Bagdy G. Opposing local effects of endocannabinoids on the activity of noradrenergic neurons and release of noradrenaline: relevance for their role in depression and in the actions of CB(1) receptor antagonists. J Neural Transm. 2013;120(1):177-86.
45. Haj-Dahmane S, Shen RY. Modulation of the serotonin system by endocannabinoid signaling. Neuropharmacology. 2011;61(3):414-20.
46. Best AR, Regehr WG. Serotonin evokes endocannabinoid release and retrogradely suppresses excitatory synapses. J Neurosci. 2008;28(25):6508-15.
47. Sigel E, et al. The major central endocannabinoid directly acts at GABA(A) receptors. Proc Natl Acad Sci USA. 2011;108(44):18150-5.
48. Spivak CE, Lupica CR, Oz M. The endocannabinoid anandamide inhibits the function of alpha4beta2 nicotinic acetylcholine receptors. Mol Pharmacol. 2007;72(4):1024-32.
49. Uriguen L, et al. Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB1 receptors. Neuropharmacology. 2004;46(7):966-73.
50. Steiner MA, et al. Impaired cannabinoid receptor type 1 signaling interferes with stress-coping behavior in mice. Pharmacogenomics J. 2008;8(3):196-208.
51. Aso E, et al. BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice. J Neurochem. 2008;105(2):565-72.
52. Parker KJ, Schatzberg AF, Lyons DM. Neuroendocrine aspects of hypercortisolism in major depression. Horm Behav. 2003;43(1):60-6.
53. Arborelius L, et al. The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol. 1999;160(1):1-12.
54. Gregus A, et al. Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats. Behav Brain Res. 2005;156(1):105-14.
55. Vermeiren Y, et al. Brain region-specific monoaminergic correlates of neuropsychiatric symptoms in Alzheimer's disease. J Alzheimers Dis. 2014;41(3):819-33.
56. Casarejos MJ, et al. Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy. J Alzheimers Dis. 2013;35(3):525-39.
57. Palmer AM, et al. Presynaptic serotonergic dysfunction in patients with Alzheimer's disease. J Neurochem. 1987;48(1):8-15.
58. Procter AW, et al. Serotonergic pathology is not widespread in Alzheimer patients without prominent aggressive symptoms. Neurochem Res. 1992;17(9):917-22.
59. Lai MK, et al. Reduced serotonin 5-HT1A receptor binding in the temporal cortex correlates with aggressive behavior in Alzheimer disease. Brain Res. 2003;974(1-2):82-7.
60. Lanctot KL, et al. Central serotonergic activity is related to the aggressive behaviors of Alzheimer's disease. Neuropsychopharmacology. 2002;27(4):646-54.
61. Mintzer J, et al. Fenfluramine challenge test as a marker of serotonin activity in patients with Alzheimer's dementia and agitation. Biol Psychiatry. 1998;44(9):918-21.
62. Haring M, et al. Identification of the cannabinoid receptor type 1 in serotonergic cells of raphe nuclei in mice. Neuroscience. 2007;146(3):1212-9.
63. Egertova M, Cravatt BF, Elphick MR. Comparative analysis of fatty acid amide hydrolase and cb(1) cannabinoid receptor expression in the mouse brain: evidence of a widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling. Neuroscience. 2003;119(2):481-96.
64. Alexander G, et al. Increased aggression in males in transgenic Tg2576 mouse model of Alzheimer's disease. Behav Brain Res. 2011;216(1):77-83.
65. Pugh PL, et al. Non-cognitive behaviours in an APP/PS1 transgenic model of Alzheimer's disease. Behav Brain Res. 2007;178(1):18-28.
66. Ramakers IH, et al. Anxiety is related to Alzheimer cerebrospinal fluid markers in subjects with mild cognitive impairment. Psychol Med. 2013;43(5):911-20.
67. Wu J, et al. Activation of the CB2 receptor system reverses amyloid-induced memory deficiency. Neurobiol Aging. 2013;34(3):791-804.
68. Martin-Moreno AM, et al. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers beta-amyloid levels and improves cognitive performance in Tg APP 2576 mice. J Neuroinflamm. 2012;9:8.
69. Guadagna S, et al. Tau phosphorylation in human brain: relationship to behavioral disturbance in dementia. Neurobiol Aging. 2012;33(12):2798-806.
70. Holmes C, Butchart J. Systemic inflammation and Alzheimer's disease. Biochem Soc Trans. 2011;39(4):898-901.
71. Sastre M, Klockgether T, Heneka MT. Contribution of inflammatory processes to Alzheimer's disease: molecular mechanisms. Int J Dev Neurosci. 2006;24(2-3):167-76.
72. Puffenbarger RA, Boothe AC, Cabral GA. Cannabinoids inhibit LPS-inducible cytokine mRNA expression in rat microglial cells. Glia. 2000;29(1):58-69.
73. Facchinetti F, et al. Cannabinoids ablate release of TNFalpha in rat microglial cells stimulated with lypopolysaccharide. Glia. 2003;41(2):161-8.
74. van der Stelt M, et al. Endocannabinoids and beta-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels. Cell Mol Life Sci. 2006;63(12):1410-24.
75. Farkas S, et al. [(1)(2)(5)I]SD-7015 reveals fine modalities of CB(1) cannabinoid receptor density in the prefrontal cortex during progression of Alzheimer's disease. Neurochem Int. 2012;60(3):286-91.
76. Robson PJ. Therapeutic potential of cannabinoid medicines. Drug Test Anal. 2014;6(1-2):24-30.
77. Zogopoulos P, et al. The role of endocannabinoids in pain modulation. Fundam Clin Pharmacol. 2013;27(1):64-80.
78. Wiley JL, et al. CB1 cannabinoid receptor-mediated modulation of food intake in mice. Br J Pharmacol. 2005;145(3):293-300.
79. Whyte LS, et al. Cannabinoids and bone: endocannabinoids modulate human osteoclast function in vitro. Br J Pharmacol. 2012;165(8):2584-97.
80. Burston JJ, Woodhams SG. Endocannabinoid system and pain: an introduction. Proc Nutr Soc. 2014;73(1):106-17.
81. Ballard C, Corbett A. Agitation and aggression in people with Alzheimer's disease. Curr Opin Psychiatry. 2013;26(3):252-9.
82. Husebo BS, et al. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ. 2011;343:d4065.
83. Bestard JA, Toth CC. An open-label comparison of nabilone and gabapentin as adjuvant therapy or monotherapy in the management of neuropathic pain in patients with peripheral neuropathy. Pain Pract. 2011;11(4):353-68.
84. Skrabek RQ, et al. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008;9(2):164-73.
85. Wissel J, et al. Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain: a double-blind placebo-controlled cross-over trial. J Neurol. 2006;253(10):1337-41.
86. Fattore L, Fratta W. Beyond THC: the new generation of cannabinoid designer drugs. Front Behav Neurosci. 2011;5:60.
87. Hudson S, Ramsey J. The emergence and analysis of synthetic cannabinoids. Drug Test Anal. 2011;3(7-8):466-78.
88. Vardakou I, Pistos C, Spiliopoulou C. Spice drugs as a new trend: mode of action, identification and legislation. Toxicol Lett. 2010;197(3):157-62.
89. Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011;72(5):735-44.
90. CADTH Rapid Response Reports, in Nabilone for non-chemotherapy associated nausea and weight loss due to medical conditions: a review of the clinical effectiveness and guidelines. 2014, Canadian Agency for Drugs and Technologies in Health Copyright (c). Ottawa: 2014 Canadian Agency for Drugs and Technologies in Health.
91. Lemberger L, Rowe H. Clinical pharmacology of nabilone, a cannabinol derivative. Clin Pharmacol Ther. 1975;18(06):720-6.
92. Whiting PF, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313(24):2456-73.
93. Smith PH, et al. Marijuana withdrawal and aggression among a representative sample of US marijuana users. Drug Alcohol Depend. 2013;132(1-2):63-8.
94. Budney AJ, et al. Marijuana abstinence effects in marijuana smokers maintained in their home environment. Arch Gen Psychiatry. 2001;58(10):917-24.
95. Guindon J, Hohmann AG. Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain. Br J Pharmacol. 2008;153(2):319-34.
96. Han S, et al. Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists. J Med Chem. 2013;56(21):8224-56.
97. Lee JH, et al. Intact cannabinoid CB1 receptors in the Alzheimer's disease cortex. Neurochem Int. 2010;57(8):985-9.