Skip to main content

A Systematic Review of the Neurocognitive Effects of Cannabis Use in Older Adults

Abstract

Purpose of Review

Older adults currently represent the fastest growing demographic of cannabis users, yet few studies have investigated the effects of cannabis use on cognitive functioning in aging. We conducted a systematic review of the recent literature examining cognitive outcomes associated with cannabis use in older adults, with and without neurocognitive disorders, to clarify the potential neuroprotective benefits or risks of cognitive decline in this population.

Recent Findings

We identified 26 studies examining cognitive outcomes associated with medical and recreational use of cannabis in healthy aging, dementia, Parkinson’s disease, multiple sclerosis, HIV, and pain populations. Although variability in the cannabis products used, outcomes assessed, and study quality limits the conclusions that can be made, modest reductions in cognitive performance were generally detected with higher doses and heavier lifetime use.

Summary

This review highlights the need for additional high-quality research using standardized, validated assessments of cannabis exposure and cognitive outcomes. Reliable measures and longitudinal data are necessary to better characterize the effects of cannabis use on cognitive aging, as well as differential effects of recreational and medical cannabis.

This is a preview of subscription content, access via your institution.

Fig. 1

References

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

    No studies of major importance were identified; the highest quality studies included in this review either did not directly address cognitive outcomes or did not focus on older adults.

    1. 1.

      • Lloyd SL, Striley CW. Marijuana use among adults 50 years or older in the 21st century. Gerontol Geriatr Med. 2018;4:233372141878166 This paper reviews the epidemiological literature from 2000 to 2017 on marijuana use among older adults, and shows that adults ages 65 and older have had the greatest increase in marijuana use over time.

      Article  Google Scholar 

    2. 2.

      Han BH, Sherman S, Mauro PM, Martins SS, Rotenberg J, Palamar JJ. Demographic trends among older cannabis users in the United States, 2006-13: cannabis use among older adults. Addiction. 2017;112:516–25.

      PubMed  Article  Google Scholar 

    3. 3.

      Han BH, Palamar JJ. Marijuana use by middle-aged and older adults in the United States, 2015–2016. Drug Alcohol Depend. 2018;191:374–81.

      PubMed  PubMed Central  Article  Google Scholar 

    4. 4.

      Colliver JD, Compton WM, Gfroerer JC, Condon T. Projecting drug use among aging baby boomers in 2020. Ann Epidemiol. 2006;16:257–65.

      PubMed  Article  Google Scholar 

    5. 5.

      Boehnke KF, Gangopadhyay S, Clauw DJ, Haffajee RL. Qualifying conditions of medical cannabis license holders in the United States. Health Aff Proj Hope. 2019;38:295–302.

      Article  Google Scholar 

    6. 6.

      Crane NA, Schuster RM, Fusar-Poli P, Gonzalez R. Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences. Neuropsychol Rev. 2013;23:117–37.

      PubMed  Article  Google Scholar 

    7. 7.

      Gorey C, Kuhns L, Smaragdi E, Kroon E, Cousijn J. Age-related differences in the impact of cannabis use on the brain and cognition: a systematic review. Eur Arch Psychiatry Clin Neurosci. 2019;269:37–58.

      PubMed  PubMed Central  Article  Google Scholar 

    8. 8.

      • Nader DA, Sanchez ZM. Effects of regular cannabis use on neurocognition, brain structure, and function: a systematic review of findings in adults. Am J Drug Alcohol Abuse. 2018;44:4–18 This systematic review examines recent studies on the effects of regular cannabis use on cognition, brain structure, and function in adults, which show that regular cannabis use is associated with mild cognitive and brain changes in adults. This review highlights important questions that remain regarding whether or not these changes are consequent to or precede the onset of cannabis use.

      PubMed  Article  Google Scholar 

    9. 9.

      Broyd SJ, van Hell HH, Beale C, Yücel M, Solowij N. Acute and chronic effects of cannabinoids on human cognition—a systematic review. Biol Psychiatry. 2016;79:557–67.

      CAS  Article  Google Scholar 

    10. 10.

      Harada CN, Natelson Love MC, Triebel KL. Normal cognitive aging. Clin Geriatr Med. 2013;29:737–52.

      PubMed  PubMed Central  Article  Google Scholar 

    11. 11.

      Corsonello A, Pedone C, Incalzi RA. Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions. Curr Med Chem. 2010;17:571–84.

      CAS  PubMed  Article  Google Scholar 

    12. 12.

      van den Elsen GAH, AIA A, 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.

      PubMed  Article  CAS  Google Scholar 

    13. 13.

      Suliman NA, Taib CNM, Moklas MAM, Basir R. Delta-9-tetrahydrocannabinol (∆9-THC) induce neurogenesis and improve cognitive performances of male Sprague Dawley rats. Neurotox Res. 2018;33:402–11.

      CAS  PubMed  Article  Google Scholar 

    14. 14.

      Martin-Moreno AM, Brera B, Spuch C, Carro E, Garcia-Garcia L, Delgado M, et al. Prolonged oral cannabinoid administration prevents neuroinflammation, lowers beta-amyloid levels and improves cognitive performance in Tg APP 2576 mice. J Neuroinflammation. 2012;9:8.

      CAS  PubMed  PubMed Central  Article  Google Scholar 

    15. 15.

      Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML. Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci. 2005;25:1904–13.

      CAS  PubMed  PubMed Central  Article  Google Scholar 

    16. 16.

      Bilkei-Gorzo A, Albayram O, Draffehn A, Michel K, Piyanova A, Oppenheimer H, et al. A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nat Med. 2017;23:782–7.

      CAS  PubMed  Article  Google Scholar 

    17. 17.

      Sarne Y, Toledano R, Rachmany L, Sasson E, Doron R. Reversal of age-related cognitive impairments in mice by an extremely low dose of tetrahydrocannabinol. Neurobiol Aging. 2018;61:177–86.

      CAS  PubMed  Article  Google Scholar 

    18. 18.

      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;24:1000–3.

      PubMed  PubMed Central  Article  Google Scholar 

    19. 19.

      Liu CS, Chau SA, Ruthirakuhan M, Lanctôt KL, Herrmann N. Cannabinoids for the treatment of agitation and aggression in Alzheimer’s disease. CNS Drugs. 2015;29:615–23.

      CAS  PubMed  Article  Google Scholar 

    20. 20.

      Weier M, Hall W. The use of cannabinoids in treating dementia. Curr Neurol Neurosci Rep. 2017;17:1–9. https://doi.org/10.1007/s11910-017-0766-6.

      CAS  Article  Google Scholar 

    21. 21.

      • Hillen JB, Soulsby N, Alderman C, Caughey GE. Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia: a systematic review. Ther Adv Drug Saf. 2019;10:204209861984699 This systematic review comprehensively examines the evidence of the effectiveness and safety of cannabinoids in the treatment of neuropsychiatric symptoms of dementia. This paper highlights limitations in the current evidence base and provides recommendations for conducting future trials.

      Article  Google Scholar 

    22. 22.

      Chandra S, Radwan MM, Majumdar CG, Church JC, Freeman TP, ElSohly MA. New trends in cannabis potency in USA and Europe during the last decade (2008–2017). Eur Arch Psychiatry Clin Neurosci. 2019;269:5–15.

      PubMed  Article  Google Scholar 

    23. 23.

      Sexton M, Cuttler C, Mischley LK. A survey of cannabis acute effects and withdrawal symptoms: differential responses across user types and age. J Altern Complement Med. 2019;25:326–35.

      PubMed  PubMed Central  Article  Google Scholar 

    24. 24.

      Kolla NJ, van der Maas M, Toplak ME, Erickson PG, Mann RE, Seeley J, et al. Adult attention deficit hyperactivity disorder symptom profiles and concurrent problems with alcohol and cannabis: sex differences in a representative, population survey. BMC Psychiatry. 2016;16:50.

      PubMed  PubMed Central  Article  CAS  Google Scholar 

    25. 25.

      Auer R, Vittinghoff E, Yaffe K, et al. Association between lifetime marijuana use and cognitive function in middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. JAMA Intern Med. 2016;176:352–61.

      PubMed  PubMed Central  Article  Google Scholar 

    26. 26.

      McKetin R, Parasu P, Cherbuin N, Eramudugolla R, Anstey KJ. A longitudinal examination of the relationship between cannabis use and cognitive function in mid-life adults. Drug Alcohol Depend. 2016;169:134–40.

      PubMed  Article  Google Scholar 

    27. 27.

      Burggren AC, Siddarth P, Mahmood Z, London ED, Harrison TM, Merrill DA, et al. Subregional hippocampal thickness abnormalities in older adults with a history of heavy cannabis use. Cannabis Cannabinoid Res. 2018;3:242–51.

      PubMed  PubMed Central  Article  Google Scholar 

    28. 28.

      Thayer RE, YorkWilliams SL, Hutchison KE, Bryan AD. Preliminary results from a pilot study examining brain structure in older adult cannabis users and nonusers. Psychiatry Res Neuroimaging. 2019;285:58–63.

      PubMed  PubMed Central  Article  Google Scholar 

    29. 29.

      Ahmed AI, van den Elsen GA, Colbers A, van der Marck MA, Burger DM, Feuth TB, et al. Safety and pharmacokinetics of oral delta-9-tetrahydrocannabinol in healthy older subjects: a randomized controlled trial. Eur Neuropsychopharmacol. 2014;24:1475–82.

      CAS  PubMed  Article  Google Scholar 

    30. 30.

      Ahmad R, Goffin K, Van den Stock J, De Winter FL, Cleeren E, Bormans G, et al. In vivo type 1 cannabinoid receptor availability in Alzheimer’s disease. Eur Neuropsychopharmacol. 2014;24:242–50.

      CAS  PubMed  Article  Google Scholar 

    31. 31.

      Altamura C, Ventriglia M, Martini MG, Montesano D, Errante Y, Piscitelli F, et al. Elevation of plasma 2-arachidonoylglycerol levels in Alzheimer’s disease patients as a potential protective mechanism against neurodegenerative decline. J Alzheimers Dis. 2015;46:497–506.

      CAS  PubMed  Article  Google Scholar 

    32. 32.

      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;51:15–9.

      CAS  PubMed  Article  Google Scholar 

    33. 33.

      van den Elsen GAH, Ahmed AIA, Verkes RJ, Feuth T, van der Marck MA, Olde Rikkert MGM. Tetrahydrocannabinol in behavioral disturbances in dementia: a crossover randomized controlled trial. Am J Geriatr Psychiatry. 2015;23:1214–24.

      PubMed  Article  Google Scholar 

    34. 34.

      Herrmann N, Ruthirakuhan M, Gallagher D, Verhoeff NPLG, Kiss A, Black SE, et al. Randomized placebo-controlled trial of nabilone for agitation in Alzheimer’s disease. Am J Geriatr Psychiatry. 2019;27(11):1161–73 S1064748119303550.

      PubMed  Article  Google Scholar 

    35. 35.

      van den Elsen GAH, Ahmed AIA, Verkes R-J, Kramers C, Feuth T, Rosenberg PB, et al. Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: a randomized controlled trial. Neurology. 2015;84:2338–46.

      PubMed  PubMed Central  Article  CAS  Google Scholar 

    36. 36.

      Balash Y, Bar-Lev Schleider L, Korczyn AD, Shabtai H, Knaani J, Rosenberg A, et al. Medical cannabis in Parkinson disease: real-life patientsʼ experience. Clin Neuropharmacol. 2017;40:268–72.

      PubMed  Article  Google Scholar 

    37. 37.

      Kindred JH, Li K, Ketelhut NB, Proessl F, Fling BW, Honce JM, et al. Cannabis use in people with Parkinson’s disease and multiple sclerosis: a web-based investigation. Complement Ther Med. 2017;33:99–104.

      PubMed  Article  Google Scholar 

    38. 38.

      Chagas MH, Zuardi AW, Tumas V, Pena-Pereira MA, Sobreira ET, Bergamaschi MM, et al. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. J Psychopharmacol. 2014;28:1088–98.

      PubMed  Article  CAS  Google Scholar 

    39. 39.

      Kindred JH, Honce JM, Kwak JJ, Rudroff T. Multiple sclerosis, cannabis use, and clinical disability: a preliminary [18 F]-fluorodeoxyglucose positron emission tomography study. Cannabis Cannabinoid Res. 2018;3:213–8.

      CAS  PubMed  PubMed Central  Article  Google Scholar 

    40. 40.

      Castelli L, Prosperini L, Pozzilli C. Balance worsening associated with nabiximols in multiple sclerosis. Mult Scler J. 2019;25:113–7.

      CAS  Article  Google Scholar 

    41. 41.

      Ball S, Vickery J, Hobart J, et al. The cannabinoid use in progressive inflammatory brain disease (CUPID) trial: a randomised double-blind placebo-controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis. Health Technol Assess. 2015;19:1–188.

      Article  Google Scholar 

    42. 42.

      Schouten J, Su T, Wit FW, et al. Determinants of reduced cognitive performance in HIV-1-infected middle-aged men on combination antiretroviral therapy. Aids. 2016;30:1027–38.

      CAS  PubMed  Article  Google Scholar 

    43. 43.

      De Francesco D, Underwood J, Bagkeris E, et al. Depression, lifestyle factors and cognitive function in people living with HIV and comparable HIV-negative controls. HIV Med. 2019;20:274–85.

      PubMed  PubMed Central  Article  Google Scholar 

    44. 44.

      Saloner R, Campbell LM, Serrano V, Montoya JL, Pasipanodya E, Paolillo EW, et al. Neurocognitive SuperAging in older adults living with HIV: demographic, neuromedical and everyday functioning correlates. J Int Neuropsychol Soc. 2019;25:507–19.

      PubMed  PubMed Central  Article  Google Scholar 

    45. 45.

      Okafor CN, Plankey MW, Li M, Chen X, Surkan PJ, Shoptaw S, et al. Association of marijuana use with changes in cognitive processing speed and flexibility for 17 years in HIV-seropositive and HIV-seronegative men. Subst Use Misuse. 2019;54:525–37.

      PubMed  PubMed Central  Article  Google Scholar 

    46. 46.

      Zaki P, Blake A, Wolt A, et al. The use of medical cannabis in cancer patients. J Pain Manag. 2017;10:353–62.

      Google Scholar 

    47. 47.

      Bar-Sela G, Tauber D, Mitnik I, Sheinman-Yuffe H, Bishara-Frolova T, Aharon-Peretz J. Cannabis-related cognitive impairment: a prospective evaluation of possible influences on patients with cancer during chemotherapy treatment as a pilot study. Anti-Cancer Drugs. 2019;30:91–7.

      CAS  PubMed  Article  Google Scholar 

    48. 48.

      Wallace MS, Marcotte TD, Umlauf A, Gouaux B, Atkinson JH. Efficacy of inhaled cannabis on painful diabetic neuropathy. J Pain. 2015;16:616–27.

      CAS  PubMed  PubMed Central  Article  Google Scholar 

    49. 49.

      Bilkei-Gorzo A. The endocannabinoid system in normal and pathological brain ageing. Philos Trans R Soc Lond Ser B Biol Sci. 2012;367:3326–41.

      CAS  Article  Google Scholar 

    50. 50.

      Gershon RC, Wagster MV, Hendrie HC, Fox NA, Cook KF, Nowinski CJ. NIH toolbox for assessment of neurological and behavioral function. Neurology. 2013;80:S2–6.

      PubMed  PubMed Central  Article  Google Scholar 

    51. 51.

      Corrada MM, Brookmeyer R, Paganini-Hill A, Berlau D, Kawas CH. Dementia incidence continues to increase with age in the oldest old the 90+ study. Ann Neurol. 2010;67:114–21.

      PubMed  PubMed Central  Article  Google Scholar 

    52. 52.

      Jorm AF, Jolley D. The incidence of dementia: a meta-analysis. Neurology. 1998;51:728–33.

      CAS  PubMed  Article  Google Scholar 

    53. 53.

      Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology. 2013;80:1778–83.

      PubMed  PubMed Central  Article  Google Scholar 

    54. 54.

      Cassano T, Calcagnini S, Pace L, Marco FD, Romano A, Gaetani S. Cannabinoid receptor 2 signaling in neurodegenerative disorders: From pathogenesis to a promising therapeutic target. Front Neurosci. 2017. https://doi.org/10.3389/fnins.2017.00030.

    55. 55.

      Bedse G, Romano A, Lavecchia AM, Cassano T, Gaetani S. The role of endocannabinoid signaling in the molecular mechanisms of neurodegeneration in Alzheimer’s disease. J Alzheimers Dis. 2015;43:1115–36.

      CAS  PubMed  Article  Google Scholar 

    56. 56.

      Aso E, Ferrer I. Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic. Front Pharmacol. 2014. https://doi.org/10.3389/fphar.2014.00037.

    57. 57.

      Talarico G, Trebbastoni A, Bruno G, de Lena C. Modulation of the cannabinoid system: a new perspective for the treatment of the Alzheimer’s disease. Curr Neuropharmacol. 2019;17:176–83.

      CAS  PubMed  Article  Google Scholar 

    58. 58.

      Aso E, Sánchez-Pla A, Vegas-Lozano E, Maldonado R, Ferrer I. Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 mice. J Alzheimers Dis JAD. 2015;43:977–91.

      CAS  PubMed  Article  Google Scholar 

    59. 59.

      Casarejos MJ, Perucho J, Gomez A, Muñoz MP, Fernandez-Estevez M, Sagredo O, et al. Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy. J Alzheimers Dis JAD. 2013;35:525–39.

      CAS  PubMed  Article  Google Scholar 

    60. 60.

      Koppel J, Bradshaw H, Goldberg TE, Khalili H, Marambaud P, Walker MJ, et al. Endocannabinoids in Alzheimer’s disease and their impact on normative cognitive performance: a case-control and cohort study. Lipids Health Dis. 2009;8:2.

      PubMed  PubMed Central  Article  CAS  Google Scholar 

    61. 61.

      de Lau LML, Breteler MMB. Epidemiology of Parkinson’s disease. Lancet Neurol. 2006;5:525–35.

      Article  Google Scholar 

    62. 62.

      Hely MA, Reid WGJ, Adena MA, Halliday GM, Morris JGL. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord Off J Mov Disord Soc. 2008;23:837–44.

      Article  Google Scholar 

    63. 63.

      Buter TC, van den Hout A, Matthews FE, Larsen JP, Brayne C, Aarsland D. Dementia and survival in Parkinson disease: a 12-year population study. Neurology. 2008;70:1017–22.

      CAS  PubMed  Article  Google Scholar 

    64. 64.

      Babayeva M, Assefa H, Basu P, Chumki S, Loewy Z. Marijuana compounds: a nonconventional approach to Parkinson’s disease therapy. Park Dis. 2016. https://doi.org/10.1155/2016/1279042.

    65. 65.

      Buhmann C, Mainka T, Ebersbach G, Gandor F. Evidence for the use of cannabinoids in Parkinson’s disease. J Neural Transm. 2019;126:913–24.

      PubMed  Article  Google Scholar 

    66. 66.

      Mendes T, Ginó S, Ribeiro F, Guerreiro M, de Sousa G, Ritchie K, et al. Memory complaints in healthy young and elderly adults: reliability of memory reporting. Aging Ment Health. 2008;12:177–82.

      PubMed  Article  Google Scholar 

    67. 67.

      Reid LM, MacLullich AMJ. Subjective memory complaints and cognitive impairment in older people. Dement Geriatr Cogn Disord. 2006;22:471–85.

      PubMed  Article  Google Scholar 

    68. 68.

      Nielsen S, Germanos R, Weier M, Pollard J, Degenhardt L, Hall W, et al. The use of cannabis and cannabinoids in treating symptoms of multiple sclerosis: a systematic review of reviews. Curr Neurol Neurosci Rep. 2018;18:8.

      PubMed  Article  CAS  Google Scholar 

    69. 69.

      Yadav V, Bever C, Bowen J, Bowling A, Weinstock-Guttman B, Cameron M, et al. Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2014;82:1083–92.

      PubMed  PubMed Central  Article  Google Scholar 

    70. 70.

      Rice J, Cameron M. Cannabinoids for treatment of MS symptoms: state of the evidence. Curr Neurol Neurosci Rep. 2017;18:1–10. https://doi.org/10.1007/s11910-018-0859-x.

      CAS  Article  Google Scholar 

    71. 71.

      Benedict RH, DeLuca J, Phillips G, LaRocca N, Hudson LD, Rudick R. Validity of the symbol digit modalities test as a cognition performance outcome measure for multiple sclerosis. Mult Scler J. 2017;23:721–33.

      Article  Google Scholar 

    72. 72.

      Alford K, Vera JH. Cognitive impairment in people living with HIV in the ART era: a review. Br Med Bull. 2018;127:55–68.

      CAS  PubMed  Article  Google Scholar 

    73. 73.

      Skalski LM, Towe SL, Sikkema KJ, Meade CS. The impact of marijuana use on memory in HIV- infected patients: a comprehensive review of the HIV and marijuana literatures. Curr Drug Abuse Rev. 2016;9:126–41.

      CAS  PubMed  Article  Google Scholar 

    74. 74.

      Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313:2456.

      CAS  PubMed  Article  Google Scholar 

    75. 75.

      Colizzi M, Bhattacharyya S. Does cannabis composition matter? Differential effects of delta-9-tetrahydrocannabinol and cannabidiol on human cognition. Curr Addict Rep. 2017;4:62–74.

      PubMed  PubMed Central  Article  Google Scholar 

    Download references

    Author information

    Affiliations

    Authors

    Corresponding author

    Correspondence to Andreana Benitez.

    Ethics declarations

    Conflict of Interest

    The authors declare that they have no conflicts of interest.

    Human and Animal Rights and Informed Consent

    This article does not contain any studies with human or animal subjects performed by any of the authors.

    Additional information

    Publisher’s Note

    Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

    This article is part of the Topical Collection on Cannabis

    Electronic supplementary material

    ESM 1

    (DOCX 29.3 kb)

    Rights and permissions

    Reprints and Permissions

    About this article

    Verify currency and authenticity via CrossMark

    Cite this article

    Scott, E.P., Brennan, E. & Benitez, A. A Systematic Review of the Neurocognitive Effects of Cannabis Use in Older Adults. Curr Addict Rep 6, 443–455 (2019). https://doi.org/10.1007/s40429-019-00285-9

    Download citation

    Keywords

    • Cannabis
    • Marijuana
    • Aging
    • Cognition
    • Neuropsychological
    • Neurodegenerative disease