Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-10T08:14:28.314Z Has data issue: false hasContentIssue false
  • English
  • Français

Association Between Interleukin-6 and Neurocognitive Performance as a Function of Self-Reported Lifetime Marijuana Use in a Community Based Sample of African American Adults

Published online by Cambridge University Press:  22 September 2014

Larry Keen II  and
Arlener D. Turner
Larry Keen II*
Affiliation:
Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida
Arlener D. Turner
Affiliation:
Center of Excellence on Disparities in HIV and Aging, Rush University Medical Center, Chicago, Illinois
*
Correspondence and reprint requests to: Larry Keen, Jr., Clinical and Health Psychology, University of Florida, 2251 Center Drive, Room 3140, Gainesville, FL 32608. E-mail: larrydkeenii@phhp.ufl.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

The purpose of the current study was to determine if self-reported lifetime marijuana use moderates the relationship between interleukin-6 (IL-6) and neurocognitive performance. Participants included 161 African American adults (50.3% women), with a mean age of 45.24 (SD=11.34). Serum was drawn upon entry into the study and participants completed a demographic questionnaire, which included drug use history, and a battery of neuropsychological tests. Using multiple regression analyses and adjusting for demographic covariates, the interaction term comprised of IL-6 and self-reported lifetime marijuana use was significantly associated with poorer performance on the Written (β=−.116; SE=.059; p=.049) and Oral trials (β=−.143; SE=.062; p=.022) of the Symbol Digit Modalities Test, as well as the Trail Making Test trial A (β=.157; SE=.071; p=.028). Current findings support previous literature, which presents the inverse relationship between IL-6 and neurocognitive dysfunction. The potential protective properties of marijuana use in African Americans, who are at increased risk for inflammatory diseases, are discussed. (JINS, 2014, 20, 773–783)

Keywords

Proinflammatory cytokineCannabisExecutive functionPsychomotor speedInflammationCognition
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 20 , Issue 8 , September 2014 , pp. 773 - 783
Copyright
Copyright © The International Neuropsychological Society 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Albayram, O., Alferink, J., Pitsch, J., Piyanova, A., Neitzert, K., Poppensieker, K., & Bilkei-Gorzo, A. (2011). Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging. Proceedings of the National Academy of Sciences of the United States of America, 108(27), 11256–11261. doi: 10.1073/pnas.1016442108 CrossRefGoogle ScholarPubMed
Baker, D., Pryce, G., Giovannoni, G., & Thompson, A.J. (2003). The therapeutic potential of cannabis. The Lancet Neurology, 2(5), 291–298. doi: 10.1016/s1474-4422(03)00381-8 CrossRefGoogle ScholarPubMed
Baldwin, G.C., Tashkin, D.P., Buckley, D.M., Park, A.N., Dubinett, S.M., & Roth, M.D. (1997). Marijuana and cocaine impair alveolar macrophage function and cytokine production. American Journal of Respiratory and Critical Care Medicine, 156(5), 1606–1613. doi: 10.1164/ajrccm.156.5.9704146 CrossRefGoogle ScholarPubMed
Barichello, T., Ceretta, R.A., Generoso, J.S., Moreira, A.P., Simoes, L.R., Comim, C.M., & Teixeira, A.L. (2012). Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis. European Journal of Pharmacology, 697(1-3), 158–164. doi: 10.1016/j.ejphar.2012.09.053 CrossRefGoogle ScholarPubMed
Berg, E.A. (1948). A simple objective technique for measuring flexibility in thinking. Journal of General Psychology, 39, 15–22. doi: 10.1080/00221309.1948.9918159 CrossRefGoogle ScholarPubMed
Black, P.H. (2003). The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain, Behavior, and Immunity, 17(5), 350–364.CrossRefGoogle ScholarPubMed
Block, R.I., & Ghoneim, M.M. (1993). Effects of chronic marijuana use on human cognition. Psychopharmacology, 110(1-2), 219–228.CrossRefGoogle ScholarPubMed
Bolla, K.I., Brown, K., Eldreth, D., Tate, K., & Cadet, J.L. (2002). Dose-related neurocognitive effects of marijuana use. Neurology, 59(9), 1337–1343.CrossRefGoogle ScholarPubMed
Cabral, G.A., & Griffin-Thomas, L. (2008). Cannabinoids as therapeutic agents for ablating neuroinflammatory disease. Endocrine, Metabolic & Immune Disorders Drug Targets, 8(3), 159–172.CrossRefGoogle ScholarPubMed
Cabral, G.A., & Griffin-Thomas, L. (2009). Emerging role of the cannabinoid receptor CB2 in immune regulation: Therapeutic prospects for neuroinflammation. Expert Reviews in Molecular Medicine, 11, e3. doi: 10.1017/S1462399409000957 CrossRefGoogle ScholarPubMed
Campbell, V.A., & Gowran, A. (2007). Alzheimer's disease; taking the edge off with cannabinoids? British Journal of Pharmacology, 152(5), 655–662. doi: 10.1038/sj.bjp.0707446 CrossRefGoogle ScholarPubMed
Canvin, J.M., & el-Gabalawy, H.S. (1999). Anti-inflammatory therapy. Physical Medicine and Rehabilitation Clinics of North America, 10(2), 301–317.CrossRefGoogle ScholarPubMed
Chang, Y.H., Lee, S.T., & Lin, W.W. (2001). Effects of cannabinoids on LPS-stimulated inflammatory mediator release from macrophages: Involvement of eicosanoids. Journal of Cellular Biochemistry, 81(4), 715–723.CrossRefGoogle ScholarPubMed
Cotto, J., Davis, E., Dowling, G., Elcano, J., Staton, A., & Weiss, S. (2010). Gender effects on drug use, abuse, and dependence: A special analysis of results from the National Survey on Drug Use and Health. Gender Medicine, 7, 402–413.CrossRefGoogle ScholarPubMed
Crean, R.D., Crane, N.A., & Mason, B.J. (2011). An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. Journal of Addiction Medicine, 5(1), 1–8. doi: 10.1097/ADM.0b013e31820c23fa CrossRefGoogle ScholarPubMed
Curran, H.V., Brignell, C., Fletcher, S., Middleton, P., & Henry, J. (2002). Cognitive and subjective dose-response effects of acute oral Delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology, 164(1), 61–70. doi: 10.1007/s00213-002-1169-0 CrossRefGoogle ScholarPubMed
Durst, R., Danenberg, H., Gallily, R., Mechoulam, R., Meir, K., Grad, E., & Lotan, C. (2007). Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. American Journal of Physiology: Heart and Circulatory Physiology, 293(6), H3602–H3607. doi: 10.1152/ajpheart.00098.2007 Google ScholarPubMed
Flory, K., Lynam, D., Milich, R., Leukefeld, C., & Clayton, R. (2002). The relations among personality, symptoms of alcohol and marijuana abuse, and symptoms of comorbid psychopathology: Results from a community sample. Experimental and Clinical Psychopharmacology, 10(4), 425–434. doi: 10.1037//1064-1297.10.4.425 CrossRefGoogle ScholarPubMed
Glass, C.K., Saijo, K., Winner, B., Marchetto, M.C., & Gage, F.H. (2010). Mechanisms underlying inflammation in neurodegeneration. Cell, 140(6), 918–934. doi: 10.1016/j.cell.2010.02.016 CrossRefGoogle ScholarPubMed
Golden, C. (1978). Stroop Color and Word Test: A manual for clinical and experimental uses. Chicago, IL: Stoelting Company.Google Scholar
Gonzalez, R. (2007). Acute and non-acute effects of cannabis on brain functioning and neuropsychological performance. Neuropsychology Review, 17(3), 347–361. doi: 10.1007/s11065-007-9036-8 CrossRefGoogle ScholarPubMed
Gorelick, P.B. (2010). Role of inflammation in cognitive impairment: Results of observational epidemiological studies and clinical trials. Annals of the New York Academy of Sciences, 1207, 155–162. doi: 10.1111/j.1749-6632.2010.05726.x CrossRefGoogle Scholar
Gowran, A., Noonan, J., & Campbell, V.A. (2011). The multiplicity of action of cannabinoids: Implications for treating neurodegeneration. CNS Neuroscience & Therapeutics, 17(6), 637–644. doi: 10.1111/j.1755-5949.2010.00195.x CrossRefGoogle ScholarPubMed
Grant, D.A., & Berg, E.A. (1948). A behavioral analysis of degree of reinforcement and ease of shifting to new responses in a Weigl-type card-sorting problem. Journal of Experimental Psychology, 38(4), 404–411.CrossRefGoogle Scholar
Grant, I., Gonzalez, R., Carey, C.L., Natarajan, L., & Wolfson, T. (2003). Non-acute (residual) neurocognitive effects of cannabis use: A meta-analytic study. Journal of the International Neuropsychological Society, 9(5), 679–689. doi: 10.1017/s1355617703950016 CrossRefGoogle ScholarPubMed
Grant, J.E., Chamberlain, S.R., Schreiber, L., & Odlaug, B.L. (2012). Neuropsychological deficits associated with cannabis use in young adults. Drug and Alcohol Dependence, 121(1-2), 159–162. doi: 10.1016/j.drugalcdep.2011.08.015 CrossRefGoogle ScholarPubMed
Greineisen, W.E., & Turner, H. (2010). Immunoactive effects of cannabinoids: Considerations for the therapeutic use of cannabinoid receptor agonists and antagonists. International Immunopharmacology, 10(5), 547–555. doi: 10.1016/j.intimp.2010.02.012 CrossRefGoogle ScholarPubMed
Hayes, A.F., & Matthes, J. (2009). Computational procedures for probing interactions in OLS and logistic regression: SPSS and SAS implementations. Behavior Research Methods, 41(3), 924–936. doi: 10.3758/BRM.41.3.924 CrossRefGoogle ScholarPubMed
Hazekamp, A., & Franjo, G. (2010). Review on clinical studies with cannabis and cannabinoids 2005–2009. Canabinoids 5 (Special Issue), 1–21.Google Scholar
Heaton, R.K., & PARStaff (2003). Wisconsin Card Sorting Test: Computer version 4. Odessa, FL: Psychological Assessment Resources, Inc.Google Scholar
Hezode, C., Roudot-Thoraval, F., Nguyen, S., Grenard, P., Julien, B., Zafrani, E.S., & Mallat, A. (2005). Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology, 42(1), 63–71. doi: 10.1002/hep.20733 CrossRefGoogle ScholarPubMed
Ishida, J.H., Peters, M.G., Jin, C., Louie, K., Tan, V., Bacchetti, P., & Terrault, N.A. (2008). Influence of cannabis use on severity of hepatitis C disease. Clinical Gastroenterology and Hepatology, 6(1), 69–75. doi: 10.1016/j.cgh.2007.10.021 CrossRefGoogle ScholarPubMed
Iversen, L. (2003). Cannabis and the brain. Brain, 126(Pt 6), 1252–1270.CrossRefGoogle ScholarPubMed
Jackson, S.J., Diemel, L.T., Pryce, G., & Baker, D. (2005). Cannabinoids and neuroprotection in CNS inflammatory disease. Journal of the Neurological Sciences, 233(1-2), 21–25. doi: 10.1016/j.jns.2005.03.002 CrossRefGoogle ScholarPubMed
Jordanova, V., Stewart, R., Davies, E., Sherwood, R., & Prince, M. (2007). Markers of inflammation and cognitive decline in an African-Caribbean population. International Journal of Geriatric Psychiatry, 22(10), 966–973. doi: 10.1002/gps.1772 CrossRefGoogle Scholar
Keen, L. Jr., Pereira, D., & Latimer, W. (2014). Self-reported lifetime marijuana use and interleukin-6 levels in middle-aged African Americans. Drug and Alcohol Dependence, 140, 156–160.CrossRefGoogle ScholarPubMed
Killestein, J., Uitdehaag, B.M., & Polman, C.H. (2004). Cannabinoids in multiple sclerosis: Do they have a therapeutic role? Drugs, 64(1), 1–11.CrossRefGoogle ScholarPubMed
Klein, T.W. (2005). Cannabinoid-based drugs as anti-inflammatory therapeutics. Nature Reviews: Immunology, 5(5), 400–411. doi: 10.1038/nri1602 Google ScholarPubMed
Klein, T.W., Friedman, H., & Specter, S. (1998). Marijuana, immunity and infection. Journal of Neuroimmunology, 83(1-2), 102–115.CrossRefGoogle ScholarPubMed
Kozela, E., Pietr, M., Juknat, A., Rimmerman, N., Levy, R., & Vogel, Z. (2010). Cannabinoids Delta(9)-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-kappaB and interferon-beta/STAT proinflammatory pathways in BV-2 microglial cells. Journal of Biological Chemistry, 285(3), 1616–1626. doi: 10.1074/jbc.M109.069294 CrossRefGoogle ScholarPubMed
Krabbe, K.S., Pedersen, M., & Bruunsgaard, H. (2004). Inflammatory mediators in the elderly. Experimental Gerontology, 39(5), 687–699. doi: 10.1016/j.exger.2004.01.009 CrossRefGoogle ScholarPubMed
Marchalant, Y., Brothers, H.M., & Wenk, G.L. (2008). Inflammation and aging: Can endocannabinoids help? Biomedicine and Pharmacotherapy, 62(4), 212–217. doi: 10.1016/j.biopha.2008.02.004 CrossRefGoogle ScholarPubMed
Marchetti, B., & Abbracchio, M.P. (2005). To be or not to be (inflamed)--is that the question in anti-inflammatory drug therapy of neurodegenerative disorders? Trends in Pharmacological Sciences, 26(10), 517–525. doi: 10.1016/j.tips.2005.08.007 CrossRefGoogle ScholarPubMed
Marioni, R.E., Deary, I.J., Murray, G.D., Lowe, G.D., Strachan, M.W., Luciano, M., & Price, J.F. (2011). Genetic associations between fibrinogen and cognitive performance in three Scottish cohorts. Behavior Genetics, 41(5), 691–699. doi: 10.1007/s10519-011-9449-2 CrossRefGoogle ScholarPubMed
Marsland, A.L., Petersen, K.L., Sathanoori, R., Muldoon, M.F., Neumann, S.A., Ryan, C., & Manuck, S.B. (2006). Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers. Psychosomatic Medicine, 68(6), 895–903. doi: 10.1097/01.psy.0000238451.22174.92 CrossRefGoogle ScholarPubMed
McDade, T.W., Hawkley, L.C., & Cacioppo, J.T. (2006). Psychosocial and behavioral predictors of inflammation in middle-aged and older adults: The Chicago health, aging, and social relations study. Psychosomatic Medicine, 68(3), 376–381. doi: 10.1097/01.psy.0000221371.43607.64 CrossRefGoogle Scholar
Monnet-Tschudi, F., Hazekamp, A., Perret, N., Zurich, M.G., Mangin, P., Giroud, C., & Honegger, P. (2008). Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures. Toxicology and Applied Pharmacology, 228(1), 8–16. doi: 10.1016/j.taap.2007.11.007 CrossRefGoogle ScholarPubMed
Mukhopadhyay, P., Rajesh, M., Horvath, B., Batkai, S., Park, O., Tanchian, G., & Pacher, P. (2011). Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radical Biology and Medicine, 50(10), 1368–1381. doi: 10.1016/j.freeradbiomed.2011.02.021 CrossRefGoogle ScholarPubMed
NIDA. (2012). Drug facts. Retrieved from http://www.drugabuse.gov/ Google Scholar
O’Connor, M.F., Motivals, S., Valandares, E., Olmstead, R., & Irwin, M. (2007). Sex differences in monocyte expression of IL-6: Role of autonomic mechanisms. American Journal of Physiology - Integrity and Comparitive Physiology, 293, R145–R151.CrossRefGoogle ScholarPubMed
Pattij, T., Wiskerke, J., & Schoffelmeer, A.N. (2008). Cannabinoid modulation of executive functions. European Journal of Pharmacology, 585(2-3), 458–463. doi: 10.1016/j.ejphar.2008.02.099 CrossRefGoogle ScholarPubMed
Quickfall, J., & Crockford, D. (2006). Brain neuroimaging in cannabis use: A review. Journal of Neuropsychiatry and Clinical Neurosciences, 18(3), 318–332. doi: 10.1176/appi.neuropsych.18.3.318 CrossRefGoogle ScholarPubMed
Raber, J., Sorg, O., Horn, T.F., Yu, N., Koob, G.F., Campbell, I.L., & Bloom, F.E. (1998). Inflammatory cytokines: Putative regulators of neuronal and neuro-endocrine function. Brain Research: Brain Research Reviews, 26(2-3), 320–326.CrossRefGoogle ScholarPubMed
Rafnsson, S.B., Deary, I.J., Smith, F.B., Whiteman, M.C., Rumley, A., Lowe, G.D., & Fowkes, F.G. (2007). Cognitive decline and markers of inflammation and hemostasis: The Edinburgh Artery Study. Journal of the American Geriatrics Society, 55(5), 700–707. doi: 10.1111/j.1532-5415.2007.01158.x CrossRefGoogle Scholar
Reiss, C.S. (2010). Cannabinoids and viral infections. Pharmaceuticals (Basel), 3(6), 1873–1886. doi: 10.3390/ph3061873 CrossRefGoogle ScholarPubMed
Reitan, R.M. (1958). Validity of the Trail Making Test as an indicator of organic brain damage. Perceptual and Motor Skills, 8, 271–276.CrossRefGoogle Scholar
Richardson, G.A., Ryan, C., Willford, J., Day, N.L., & Goldschmidt, L. (2002). Prenatal alcohol and marijuana exposure: Effects on neuropsychological outcomes at 10 years. Neurotoxicology and Teratology, 24(3), 309–320.CrossRefGoogle ScholarPubMed
Rom, S., & Persidsky, Y. (2013). Cannabinoid receptor 2: Potential role in immunomodulation and neuroinflammation. Journal of Neuroimmune Pharmacology, 8(3), 608–620. doi: 10.1007/s11481-013-9445-9 CrossRefGoogle ScholarPubMed
Rubino, T., Realini, N., Braida, D., Guidi, S., Capurro, V., Vigano, D., & Parolaro, D. (2009). Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus, 19(8), 763–772. doi: 10.1002/hipo.20554 CrossRefGoogle ScholarPubMed
Sartori, A.C., Vance, D.E., Slater, L.Z., & Crowe, M. (2012). The impact of inflammation on cognitive function in older adults: Implications for healthcare practice and research. Journal of Neuroscience Nursing, 44(4), 206–217. doi: 10.1097/JNN.0b013e3182527690 CrossRefGoogle Scholar
Sinha, R. (2001). How does stress increase risk of drug abuse and relapse? Psychopharmacology, 158(4), 343–359. doi: 10.1007/s002130100917 CrossRefGoogle ScholarPubMed
Smith, A. (1982). Symbol Digit Modalities (SDMT). Manual (revised). Los Angeles, CA: Western Psychological Services.Google Scholar
Tapert, S.F., Granholm, E., Leedy, N.G., & Brown, S.A. (2002). Substance use and withdrawal: Neuropsychological functioning over 8 years in youth. Journal of the International Neuropsychological Society, 8(7), 873–883.CrossRefGoogle ScholarPubMed
Teunissen, C.E., van Boxtel, M.P., Bosma, H., Bosmans, E., Delanghe, J., De Bruijn, C., & de Vente, J. (2003). Inflammation markers in relation to cognition in a healthy aging population. Journal of Neuroimmunology, 134(1-2), 142–150.CrossRefGoogle Scholar
Weckowicz, T.E., & Janssen, D.V. (1973). Cognitive functions, personality traits, and social values in heavy marijuana smokers and nonsmoker controls. Journal of Abnormal Psychology, 81(3), 264–269.CrossRefGoogle ScholarPubMed
Wilson, C.J., Cohen, H.J., & Pieper, C.F. (2003). Cross-linked fibrin degradation products (D-dimer), plasma cytokines, and cognitive decline in community-dwelling elderly persons. Journal of the American Geriatrics Society, 51(10), 1374–1381.CrossRefGoogle ScholarPubMed
Wrona, D. (2006). Neural-immune interactions: An integrative view of the bidirectional relationship between the brain and immune systems. Journal of Neuroimmunology, 172(1-2), 38–58. doi: 10.1016/j.jneuroim.2005.10.017 CrossRefGoogle ScholarPubMed