Abstract
Cannabis and other illicit drugs are often used or abused comorbidly. Two competing theories to explain this comorbidity are (i) the phenotypic causation (gateway) model and (ii) the correlated liabilities model. We used data from 1191 male and 934 female same-sex twin pairs to test 13 genetically informative models of comorbidity. Models were fit separately for use and abuse/dependence in both sexes. The correlated liabilities model provided a good fit to the data for cannabis and other illicit drug use, as well as abuse/dependence. The relationship between the use or abuse of cannabis and other illicit drugs is not entirely phenotypic, as depicted by the random multiformity of cannabis model, which is an adaptation of the gateway model. The comorbidity appears to arise from correlated genetic and environmental influences. There is some evidence for a model in which high-risk cannabis users may be at increased risk for other illicit drug use. For abuse/dependence, a model with causal pathways between the liability for cannabis and other illicit drug abuse/dependence also fits well. Overall, our results suggest that the use and abuse/dependence of cannabis and other illicit drugs are strongly linked via common risk factors that jointly influence their individual liabilities.
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Adler, I., and Kandel, D. B. (1981). Cross-cultural perspectives on developmental stages in adolescent drug use. J. Stud. Alcohol 42:701-715.
Akaike, H. (1987). Factor analysis and AIC. Psychometrika 52: 317-332.
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, D.C.: American Psychiatric Association.
Blaze-Temple, D., and Lo, S. K. (1992). Stages of drug use: A community survey of Perth teenagers. Br. J. Addict. 87:215-225.
Brook, J. S., Brook, D. W., De La, R. M., Duque, L. F., Rodriguez, E., Montoya, I. D., and Whiteman, M. (1998). Pathways to marijuana use among adolescents: Cultural/ecological, family, peer, and personality influences. J. Am. Acad. Child Adolesc. Psychiatry 37:759-766.
Brook, J. S., Hamburg, B. A., Balka, E. B., and Wynn, P. S. (1992). Sequences of drug involvement in African-American and Puerto Rican adolescents. Psychol. Rep. 71:179-182.
Cadoret, R. J., Yates, W. R., Troughton, E., Woodworth, G., and Stewart, M. A. (1995). Adoption study demonstrating two genetic pathways to drug abuse. Arch. Gen. Psychiatry 52:42-52.
Carmelli, D., Swan, G. E., Robinette, D., and Fabsitz, R. (1992). Genetic influence on smoking: A study of male twins. N. Engl. J. Med. 327:829-833.
Catalano, R. F., Hawkins, J. D., Wells, E. A., Miller, J., and Brewer, D. (1990). Evaluation of the effectiveness of adolescent drug abuse treatment, assessment of risks for relapse, and promising approaches for relapse prevention. Int. J. Addict. 25:1085-1140.
Dohrenwend, B. P. (2000). The role of adversity and stress in psychopathology: Some evidence and its implications for theory and research. J. Health Soc. Behav. 41:1-19.
Donovan, J. E., and Jessor, R. (1983). Problem drinking and the dimension of involvement with drugs: A Guttman scalogram analysis of adolescent drug use. Am. J. Public Health 73:543-552.
Donovan, J. E., and Jessor, R. (1985). Structure of problem behavior in adolescence and young adulthood. J. Consult Clin. Psychol. 53:890-904.
Ellickson, P. L., Hays, R. D., and Bell, R. M. (1992). Stepping through the drug use sequence: Longitudinal scalogram analysis of initiation and regular use. J. Abnorm. Psychol. 101:441-451.
Farrell, A. D., Danish, S. J., and Howard, C. W. (1992). Relationship between drug use and other problem behaviors in urban adolescents. J. Consult Clin. Psychol. 60:705-712.
Fergusson, D. M., and Horwood, L. J. (2000). Does cannabis use encourage other forms of illicit drug use? Addiction 95:505-520.
Fergusson, D. M., Swain-Campbell, N. R., and Horwood, L. J. (2002). Deviant peer affiliations, crime and substance use: A fixed effects regression analysis. J. Abnorm. Child Psychol. 30:419-430.
Fu, Q., Heath, A. C., Bucholz, K. K., Nelson, E., Goldberg, J., Lyons, M. J., True, W. R., Jacob, T., Tsuang, M. T., and Eisen, S. A. (2002). Shared genetic risk of major depression, alcohol dependence, and marijuana dependence: Contribution of antisocial personality disorder in men. Arch. Gen. Psychiatry 59:1125-1132.
Golub, A., and Johnson, B. D. (1994). The shifting importance of alcohol and marijuana as gateway substances among serious drug abusers. J. Stud. Alcohol 55:607-614.
Hawkins, J. D., Abbott, R., Catalano, R. F., and Gillmore, M. R. (1991). Assessing effectiveness of drug abuse prevention: Implementation issues relevant to long-term effects and replication. NIDA Res. Monogr. 107:195-212.
Hawkins, J. D., Catalano, R. F., and Miller, J. Y. (1992). Risk and protective factors for alcohol and other drug problems in adolescence and early adulthood: Implications for substance abuse prevention. Psychol Bull. 112:64-105.
Heath, A. C., Madden, P. A., Slutske, W. S., and Martin, N. G. (1995). Personality and the inheritance of smoking behavior: A genetic perspective. Behav. Genet. 25:103-117.
Hopfer, C. J., Stallings, M. C., Hewitt, J. K., and Crowley, T. J. (2003). Family transmission of marijuana use, abuse, and dependence. J. Am. Acad. Child Adolesc. Psychiatry 42:834-841.
Huba, G. J., Wingard, J. A., and Bentler, P. M. (1981). A comparison of two latent variable causal models for adolescent drug use. J. Pers. Soc. Psychol. 40:180-193.
Jang, K. L., Livesley, W. J., and Vernon, P. A. (1997). Genderspecific etiological differences in alcohol and drug problems: A behavioural genetic analysis. Addiction 92:1265-1276.
Jessor, R. (1987). Problem-behavior theory, psychosocial development, and adolescent problem drinking. Br. J. Addict. 82: 331-342.
Jessor, R., and Jessor, S. L. (1977). Problem Behavior and Psychosocial Development: A Longitudinal Study of Youth. New York: Academic Press.
Johnson, J. G., Cohen, P., Dohrenwend, B. P., Link, B. G., and Brook, J. S. (1999). A longitudinal investigation of social causation and social selection processes involved in the association between socioeconomic status and psychiatric disorders. J. Abnorm. Psychol. 108:490-499.
Kandel, D. (2002). Stages and Pathways of Drug Involvement. New York: Cambridge University Press.
Kandel, D. B., Adler, I., and Sudit, M. (1981). The epidemiology of adolescent drug use in France and Israel. Am. J. Public Health 71:256-265.
Kandel, D. B., Huang, F. Y., and Davies, M. (2001). Comorbidity between patterns of substance use dependence and psychiatric syndromes. Drug Alcohol Depend. 64:233-241.
Kandel, D. B., and Yamaguchi, K. (1985). Developmental patterns of the use of legal, illegal, and medically prescribed psychotropic drugs from adolescence to young adulthood. NIDA Res. Monogr. 56:193-235.
Kandel, D. B., Yamaguchi, K., and Chen, K. (1992). Stages of progression in drug involvement from adolescence to adulthood: Further evidence for the gateway theory. J. Stud. Alcohol 53:447-457.
Karkowski, L. M., Prescott, C. A., and Kendler, K. S. (2000). Multivariate assessment of factors influencing illicit substance use in twins from female-female pairs. Am. J. Med. Genet. 96:665-670.
Kendler, K. S., Jacobson, K. C., Prescott, C. A., and Neale, M. C. (2003). Specificity of genetic and environmental risk factors for use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates in male twins. Am. J. Psychiatry 160:687-695.
Kendler, K. S., Karkowski, L. M., Neale, M. C., and Prescott, C. A. (2000). Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins. Arch. Gen. Psychiatry 57:261-269.
Kendler, K. S., Karkowski, L., and Prescott, C. A. (1999). Hallucinogen, opiate, sedative and stimulant use and abuse in a population-based sample of female twins. Acta Psychiatr. Scand. 99:368-376.
Kendler, K. S., Neale, M. C., Kessler, R. C., Heath, A. C., and Eaves, L. J. (1992). A population-based twin study of major depression in women: The impact of varying definitions of illness. Arch. Gen. Psychiatry 49:257-266.
Kendler, K. S., and Prescott, C. A. (1998). Cocaine use, abuse and dependence in a population-based sample of female twins. Br. J. Psychiatry 173:345-350.
Kendler, K. S., and Prescott, C. A. (1999). A population-based twin study of lifetime major depression in men and women. Arc. Gen. Psychiatry 56:39-44.
Klein, D. N., and Riso, L. P. (1994). Psychiatric disorders: Problems of boundaries and comorbidity. In Costello, C. G. (ed), Basic issues in psychopathology (pp. 19-86). New York: Guilford.
Krueger, R. F., Hicks, B. M., Patrick, C. J., Carlson, S. R., Iacono, W. G., and McGue, M. (2002). Etiologic connections among substance dependence, antisocial behavior, and personality: Modeling the externalizing spectrum. J. Abnorm. Psychol. 111:411-424.
Luke, D. A., Ribisi, K. M., Walton, M. A., and Davidson, W. S. (2002). Assessing the diversity of personal beliefs about addiction: Development of the addiction belief inventory. Subst. Use Misuse. 37:89-120.
Lynskey, M. T., Heath, A. C., Bucholz, K. K., Slutske, W. S., Madden, P. A., Nelson, E. C., Statham, D. J., and Martin, N. G. (2003). Escalation of drug use in early-onset cannabis users vs co-twin controls. JAMA 289:427-433.
Lynskey, M. T., Heath, A. C., Nelson, E. C., Bucholz, K. K., Madden, P. A., Slutske, W. S., Statham, D. J., and Martin, N. G. (2002). Genetic and environmental contributions to cannabis dependence in a national young adult twin sample. Psychol. Med. 32:195-207.
Merikangas, K. R., Stolar, M., Stevens, D. E., Goulet, J., Preisig, M. A., Fenton, B., Zhang, H., O'Malley, S. S., and Rounsaville, B. J. (1998). Familial transmission of substance use disorders. Arch. Gen. Psychiatry 55:973-979.
Merrill, J. C., Kleber, H. D., Shwartz, M., Liu, H., and Lewis, S. R. (1999). Cigarettes, alcohol, marijuana, other risk behaviors, and American youth. Drug Alcohol Depend. 56:205-212.
Metten, P., and Crabbe, J. C. (1994). Common genetic determinants of severity of acute withdrawal from ethanol, pentobarbital and diazepam in inbred mice. Behav. Pharmacol. 5:533-547.
Mills, C. J., and Noyes, H. L. (1984). Patterns and correlates of initial and subsequent drug use among adolescents. J. Consult Clin. Psychol. 52:231-243.
Morral, A. R., McCaffrey, D. F., and Paddock, S. M. (2002a). Reassessing the marijuana gateway effect. Addiction 97:1493-1504.
Morral, A. R., McCaffrey, D. F., and Paddock, S. M. (2002b). Evidence does not favor marijuana gateway effects over a common-factor interpretation of drug use initiation: Responses to Anthony, Kenkel & Mathios and Lynskey. Addiction 97:1509-1510.
Neale, M. C. (1990). Statistical modeling with Mx. Department of Psychiatry, Richmond, VA: Virginia Commonwealth University.
Neale, M. C., and Kendler, K. S. (1995). Models of comorbidity for multifactorial disorders. Am. J. Hum. Genet. 57:935-953.
Pickens, R. W., Svikis, D. S., McGue, M., and LaBuda, M. C. (1995). Common genetic mechanisms in alcohol, drug, and mental disorder comorbidity. Drug Alcohol Depend. 39:129-138.
Prescott, C. A., and Kendler, K. S. (1995). Genetic and environmental influences on alcohol and tobacco dependence among women. NIAAA Res. Monogr. 30:59-87.
Rhee, S. H., Hewitt, J. K., Corley, R. P., and Stallings, M. C. (2003). The validity of analyses testing the etiology of comorbidity between two disorders: Comparisons of disorder prevalence in families. Behav. Genet. 33(3):257-69.
Slutske, W. S., Heath, A. C., Madden, P. A., Bucholz, K. K., Statham, D. J., and Martin, N. G. (2002). Personality and the genetic risk for alcohol dependence. J. Abnorm. Psychol. 111:124-133.
Spitzer, R. L., Williams, J. B., and Gibbon, J. (1997). Structured Clinical Interview for DSM-III-R: Patient Version (SCID-P). New York: New York State Psychiatric Institute.
Swan, G. E., Carmelli, D., and Cardon, L. R. (1996). The consumption of tobacco, alcohol, and coffee in Caucasian male twins: A multivariate genetic analysis. J. Subst. Abuse 8:19-31.
Tsuang, M. T., Bar, J. L., Harley, R. M., and Lyons, M. J. (2001). The Harvard Twin Study of Substance Abuse: What we have learned. Harv. Rev. Psychiatry 9:267-279.
Tsuang, M. T., Lyons, M. J., Meyer, J. M., Doyle, T., Eisen, S. A., Goldberg, J., True, W., Lin, N., Toomey, R., and Eaves, L. (1998). Co-occurrence of abuse of different drugs in men: The role of drug-specific and shared vulnerabilities. Arch. Gen. Psychiatry 55:967-972.
van den Bree, M. B., Johnson, E. O., Neale, M. C., and Pickens, R. W. (1998). Genetic and environmental influences on drug use and abuse/dependence in male and female twins. Drug Alcohol Depend. 52:231-241.
Voss, H. L., and Clayton, R. R. (1987). Stages in involvement with drugs. Pediatrician 14:25-31.
Wagner, F. A., and Anthony, J. C. (2002). Into the world of illegal drug use: Exposure opportunity and other mechanisms linking the use of alcohol, tobacco, marijuana, and cocaine. Am. J. Epidemiol. 155:918-925.
Williams, L. J., and Holahan, P. J. (2002). Parsimony-based fit indices for multiple-indicator models: Do they work? Struct. Equation Model. 1:161-189.
Willner, P. (2001). A view through the gateway: Expectancies as a possible pathway from alcohol to cannabis. Addiction 96:691-703.
Yamaguchi, K., and Kandel, D. B. (1984). Patterns of drug use from adolescence to young adulthood. III. Predictors of progression. Am. J. Public Health 74:673-681.
Young, S. E., Corley, R. P., Stallings, M. C., Rhee, S. H., Crowley, T. J., and Hewitt, J. K. (2002).Substance use, abuse and dependence in adolescence: Prevalence, symptom profiles and correlates. Drug Alcohol Depend. 68:309-322.
Young, S. E., Stallings, M. C., Corley, R. P., Krauter, K. S., and Hewitt, J. K. (2000). Genetic and environmental influences on behavioral disinhibition. Am. J. Med. Genet. 96:684-695.
Yu, J., and Williford, W. R. (1992). The age of alcohol onset and alcohol, cigarette, and marijuana use patterns: An analysis of drug use progression of young adults in New York State. Int. J. Addict. 27:1313-1323.
Zuckerman, M. (1983). Sensation seeking: The initial motive for drug use. In E. H. Gottheil, K. A. Druley, T. E. Skolada, and H. M. Waxman (eds.), Etiological Aspects of Alcohol and Drug Abuse (pp. 202-220). Springfield, IL: Charles C. Thomas.
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Agrawal, A., Neale, M.C., Prescott, C.A. et al. Cannabis and Other Illicit Drugs: Comorbid Use and Abuse/Dependence in Males and Females. Behav Genet 34, 217–228 (2004). https://doi.org/10.1023/B:BEGE.0000017868.07829.45
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DOI: https://doi.org/10.1023/B:BEGE.0000017868.07829.45