Association Between Lifetime Marijuana Use and Cognitive Function in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study | Adolescent Medicine | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Johnston  LD, O’Malley  PM, Bachman  JG, Schulenberg  JE. Monitoring the future: national results on drug use: 2012 overview: key findings on adolescent drug use. Ann Arbor: Institute for Social Research, The University of Michigan. Published February 2013. Accessed March 21, 2013.
Solowij  N.  Cannabis and Cognitive Functioning. New York, NY: Cambridge University Press; 1998.
Grant  I, Gonzalez  R, Carey  CL, Natarajan  L, Wolfson  T.  Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study.  J Int Neuropsychol Soc. 2003;9(5):679-689.PubMedGoogle ScholarCrossref
Solowij  N, Stephens  RS, Roffman  RA,  et al; Marijuana Treatment Project Research Group.  Cognitive functioning of long-term heavy cannabis users seeking treatment.  JAMA. 2002;287(9):1123-1131.PubMedGoogle ScholarCrossref
Meier  MH, Caspi  A, Ambler  A,  et al.  Persistent cannabis users show neuropsychological decline from childhood to midlife.  Proc Natl Acad Sci U S A. 2012;109(40):E2657-E2664.PubMedGoogle ScholarCrossref
Gonzalez  R, Martin  EM, Grant  I. Marijuana. In: Kalechstein  A, van Gorp  WG, eds.  Neuropsychology and Substance Use: State-of-the-Art and Future Directions. New York, NY: Taylor & Francis; 2007:139-170.
Friedman  GD, Cutter  GR, Donahue  RP,  et al.  CARDIA: study design, recruitment, and some characteristics of the examined subjects.  J Clin Epidemiol. 1988;41(11):1105-1116.PubMedGoogle ScholarCrossref
Pletcher  MJ, Vittinghoff  E, Kalhan  R,  et al.  Association between marijuana exposure and pulmonary function over 20 years.  JAMA. 2012;307(2):173-181.PubMedGoogle ScholarCrossref
Reis  JP, Loria  CM, Launer  LJ,  et al.  Cardiovascular health through young adulthood and cognitive functioning in midlife.  Ann Neurol. 2013;73(2):170-179.PubMedGoogle ScholarCrossref
Delis  DC, Kramer  JH, Kaplan  E, Ober  BA.  California Verbal Learning Test: Adult Version Manual. San Antonio, TX: The Psychological Corporation; 1987.
Wechsler  D.  Administration and Scoring Manual for the Wechsler Adult Intelligence Scale–III. London, England: Psychological Corporation; 2008.
MacLeod  CM.  Half a century of research on the Stroop effect: an integrative review.  Psychol Bull. 1991;109(2):163-203.PubMedGoogle ScholarCrossref
Stroop  JR.  Studies of interference in serial verbal reactions.  J Exp Psychol. 1935;18:643-662.Google ScholarCrossref
Auer  R, Vittinghoff  E, Kiefe  C,  et al.  Change in physical activity after smoking cessation: the Coronary Artery Risk Development in Young Adults (CARDIA) study.  Addiction. 2014;109(7):1172-1183.PubMedGoogle ScholarCrossref
Pletcher  MJ, Varosy  P, Kiefe  CI, Lewis  CE, Sidney  S, Hulley  SB.  Alcohol consumption, binge drinking, and early coronary calcification: findings from the Coronary Artery Risk Development in Young Adults (CARDIA) study.  Am J Epidemiol. 2005;161(5):423-433.PubMedGoogle ScholarCrossref
Kertesz  SG, Khodneva  Y, Richman  J,  et al.  Trajectories of drug use and mortality outcomes among adults followed over 18 years.  J Gen Intern Med. 2012;27(7):808-816.PubMedGoogle ScholarCrossref
Kertesz  SG, Pletcher  MJ, Safford  M,  et al.  Illicit drug use in young adults and subsequent decline in general health: the Coronary Artery Risk Development in Young Adults (CARDIA) study.  Drug Alcohol Depend. 2007;88(2-3):224-233.PubMedGoogle ScholarCrossref
Jacobs  DR  Jr, Hahn  LP, Haskell  WL, Pirie  P, Sidney  S.  Validity and reliability of short physical activity history: CARDIA and the Minnesota Heart Health Program.  J Cardiopulm Rehabil Prev. 1989;9(11):448-459.Google ScholarCrossref
Radloff  LS.  The CES-D scale: a self-report depression scale for research in the general population.  Appl Psychol Meas.1977;1(3):385-401. doi:10.1177/014662167700100306.Google Scholar
Yaffe  K, Vittinghoff  E, Pletcher  MJ,  et al.  Early adult to midlife cardiovascular risk factors and cognitive function.  Circulation. 2014;129(15):1560-1567.PubMedGoogle ScholarCrossref
Kasprowicz  AL, Manuck  SB, Malkoff  SB, Krantz  DS.  Individual differences in behaviorally evoked cardiovascular response: temporal stability and hemodynamic patterning.  Psychophysiology. 1990;27(6):605-619.PubMedGoogle ScholarCrossref
Zhu  N, Jacobs  DR, Meyer  KA,  et al.  Cognitive function in a middle aged cohort is related to higher quality dietary pattern 5 and 25 years earlier: the CARDIA study.  J Nutr Health Aging. 2015;19(1):33-38.PubMedGoogle ScholarCrossref
Waldstein  SR, Bachen  EA, Manuck  SB.  Active coping and cardiovascular reactivity: a multiplicity of influences.  Psychosom Med. 1997;59(6):620-625.PubMedGoogle ScholarCrossref
Gardner  RM.  The reverse affect test: a new interference task.  Percept Mot Skills. 1985;60(2):384-386.PubMedGoogle ScholarCrossref
Hernán  MA, Brumback  B, Robins  JM.  Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men.  Epidemiology. 2000;11(5):561-570.PubMedGoogle ScholarCrossref
Manrique-Garcia  E, Zammit  S, Dalman  C, Hemmingsson  T, Andreasson  S, Allebeck  P.  Cannabis, schizophrenia and other non-affective psychoses: 35 years of follow-up of a population-based cohort.  Psychol Med. 2012;42(6):1321-1328.PubMedGoogle ScholarCrossref
McLoughlin  BC, Pushpa-Rajah  JA, Gillies  D,  et al.  Cannabis and schizophrenia.  Cochrane Database Syst Rev. 2014;10:CD004837.PubMedGoogle Scholar
Hancox  RJ, Poulton  R, Ely  M,  et al.  Effects of cannabis on lung function: a population-based cohort study.  Eur Respir J. 2010;35(1):42-47.PubMedGoogle ScholarCrossref
Bild  DE, Jacobs  DR  Jr, Sidney  S, Haskell  WL, Anderssen  N, Oberman  A.  Physical activity in young black and white women: the CARDIA study.  Ann Epidemiol. 1993;3(6):636-644.PubMedGoogle ScholarCrossref
National Institute on Alcohol Abuse and Alcoholism. Helping patients who drink too much: a clinician's guide. Updated 2005. Accessed September 25, 2013.
Radloff  LS, Locke  BZ. The community mental health assessment survey and the CES-D scale. In: Weissman  MM, Myers  JK, Ross  CE, eds.  Community Surveys of Psychiatric Disorders. New Brunswick, NJ: Rutgers University Press; 1986:177-189.
Pope  HG  Jr, Yurgelun-Todd  D.  The residual cognitive effects of heavy marijuana use in college students.  JAMA. 1996;275(7):521-527.PubMedGoogle ScholarCrossref
Fried  P, Watkinson  B, James  D, Gray  R.  Current and former marijuana use: preliminary findings of a longitudinal study of effects on IQ in young adults.  CMAJ. 2002;166(7):887-891.PubMedGoogle Scholar
Levine  DA, Galecki  AT, Langa  KM,  et al.  Trajectory of cognitive decline after incident stroke.  JAMA. 2015;314(1):41-51.PubMedGoogle ScholarCrossref
Jager  G, Ramsey  NF.  Long-term consequences of adolescent cannabis exposure on the development of cognition, brain structure and function: an overview of animal and human research.  Curr Drug Abuse Rev. 2008;1(2):114-123.PubMedGoogle ScholarCrossref
Batalla  A, Bhattacharyya  S, Yücel  M,  et al.  Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings.  PLoS One. 2013;8(2):e55821.PubMedGoogle ScholarCrossref
Jager  G, Van Hell  HH, De Win  MM,  et al.  Effects of frequent cannabis use on hippocampal activity during an associative memory task.  Eur Neuropsychopharmacol. 2007;17(4):289-297.PubMedGoogle ScholarCrossref
Lorenzetti  V, Solowij  N, Fornito  A, Lubman  DI, Yucel  M.  The association between regular cannabis exposure and alterations of human brain morphology: an updated review of the literature.  Curr Pharm Des. 2014;20(13):2138-2167.PubMedGoogle ScholarCrossref
Yücel  M, Solowij  N, Respondek  C,  et al.  Regional brain abnormalities associated with long-term heavy cannabis use.  Arch Gen Psychiatry. 2008;65(6):694-701.PubMedGoogle ScholarCrossref
Tzilos  GK, Cintron  CB, Wood  JB,  et al.  Lack of hippocampal volume change in long-term heavy cannabis users.  Am J Addict. 2005;14(1):64-72.PubMedGoogle ScholarCrossref
van der Pol  P, Liebregts  N, de Graaf  R, Korf  DJ, van den Brink  W, van Laar  M.  Validation of self-reported cannabis dose and potency: an ecological study.  Addiction. 2013;108(10):1801-1808.PubMedGoogle ScholarCrossref
Rogeberg  O.  Correlations between cannabis use and IQ change in the Dunedin cohort are consistent with confounding from socioeconomic status.  Proc Natl Acad Sci U S A. 2013;110(11):4251-4254.PubMedGoogle ScholarCrossref
Moffitt  TE, Meier  MH, Caspi  A, Poulton  R.  Reply to Rogeberg and Daly: no evidence that socioeconomic status or personality differences confound the association between cannabis use and IQ decline.  Proc Natl Acad Sci U S A. 2013;110(11):E980-E982.PubMedGoogle ScholarCrossref
Pacula  RL, Sevigny  EL.  Natural experiments in a complex and dynamic environment: the need for a measured assessment of the evidence.  J Policy Anal Manage. 2014;33(1):232-235.PubMedGoogle ScholarCrossref
Volkow  ND, Baler  RD, Compton  WM, Weiss  SR.  Adverse health effects of marijuana use.  N Engl J Med. 2014;370(23):2219-2227.PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    Chronic Marijuana Use and Respiratory and Dental Disease
    Alan Herman, PhD | Freelance public health researcher
    Respiratory and dental diseases are other cautions in regard to chronic marijuana use. The inhalation of particulates in marijuana smoke, even with the use of a water pipe, makes the marijuana user, like the tobacco user, at risk for these diseases (Moore et al.,2005; Thomson, et al., 2008). The use pattern may be less marijuana cigarettes smoked than tobacco cigarettes, but the effects of using either drug is the same. The marijuana user, unlike the tobacco cigarette user, and sometimes a person uses both drugs, draws the smoke to get the THC 'high' effect and fills and holds the smoke in the mouth, bronchial tubes and lungs increasing the risks of these diseases, in the same way multiple tobacco cigarettes smoked and less smoke retention creates the same risks (Aldington et al.,2007).

    Aldington, S., Williams M., Nowitz, M., Weatherall, M., Pritchard, A., McNaughton, A., Robinson, G., Beasley, R. (2007), Effects of cannabis on pulmonary structure, function and symptoms Thorax, 62:12 1058-1063.

    Moore, B. A., Augustson, E. M., Moser, R. P., & Budney, A. J. (2005). Respiratory Effects of Marijuana and Tobacco Use in a U.S. Sample. Journal of General Internal Medicine, 20(1), 33–37.

    Thomson W, Poulton R, Broadbent JM, et al. (2008) Cannabis Smoking and Periodontal Disease Among Young Adults. JAMA, 299(5):525-531.
    Original Investigation
    March 2016

    Association Between Lifetime Marijuana Use and Cognitive Function in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

    Author Affiliations
    • 1Department of Epidemiology and Biostatistics, University of California–San Francisco
    • 2Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland
    • 3Department of Psychiatry and Neurology, University of California–San Francisco
    • 4Center for Surgical Medical and Acute Care Research, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama
    • 5Department of Medicine, University of Alabama at Birmingham School of Medicine
    • 6Department of Internal Medicine, University of Michigan Medical School, Ann Arbor
    • 7Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan
    • 8Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor
    • 9Department of Neurology and Stroke Program, University of Michigan, Ann Arbor
    • 10Department of Psychiatry, University of Geneva, Geneva, Switzerland
    • 11Kaiser Permanente Division of Research, Oakland, California
    • 12Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis
    JAMA Intern Med. 2016;176(3):352-361. doi:10.1001/jamainternmed.2015.7841

    Importance  Marijuana use is increasingly common in the United States. It is unclear whether it has long-term effects on memory and other domains of cognitive function.

    Objective  To study the association between cumulative lifetime exposure to marijuana use and cognitive performance in middle age.

    Design, Setting, and Participants  We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 black and white men and women aged 18 to 30 years at baseline from March 25, 1985, to June 7, 1986 (year 0), and followed up over 25 years from June 7, 1986, to August 31, 2011, to estimate cumulative years of exposure to marijuana (1 year = 365 days of marijuana use) using repeated measures and to assess associations with cognitive function at year 25. Linear regression was used to adjust for demographic factors, cardiovascular risk factors, tobacco smoking, use of alcohol and illicit drugs, physical activity, depression, and results of the mirror star tracing test (a measure of cognitive function) at year 2. Data analysis was conducted from June 7, 1986, to August 31, 2011.

    Main Outcomes and Measures  Three domains of cognitive function were assessed at year 25 using the Rey Auditory Verbal Learning Test (verbal memory), the Digit Symbol Substitution Test (processing speed), and the Stroop Interference Test (executive function).

    Results  Among 3385 participants with cognitive function measurements at the year 25 visit, 2852 (84.3%) reported past marijuana use, but only 392 (11.6%) continued to use marijuana into middle age. Current use of marijuana was associated with worse verbal memory and processing speed; cumulative lifetime exposure was associated with worse performance in all 3 domains of cognitive function. After excluding current users and adjusting for potential confounders, cumulative lifetime exposure to marijuana remained significantly associated with worse verbal memory. For each 5 years of past exposure, verbal memory was 0.13 standardized units lower (95% CI, −0.24 to −0.02; P = .02), corresponding to a mean of 1 of 2 participants remembering 1 word fewer from a list of 15 words for every 5 years of use. After adjustment, we found no associations with lower executive function (–0.03 [95% CI, −0.12 to 0.07]; P = .56) or processing speed (–0.04 [95% CI, −0.16 to 0.08]; P = .51).

    Conclusions and Relevance  Past exposure to marijuana is associated with worse verbal memory but does not appear to affect other domains of cognitive function.