Gateway drug theory
||It has been suggested that Tobacco and other drugs be merged into this article. (Discuss) Proposed since June 2016.|
Gateway drug theory (alternatively, stepping-stone theory, escalation hypothesis, or progression hypothesis) is a comprehensive catchphrase for the medical theory that the use of a psychoactive drug can be coupled to an increased probability of the use of further drugs. Possible causes are biological alterations in the brain due to the earlier drug and similar attitudes of users across different drugs (common liability to addiction). Scientific investigation of the possible causes is considered important for health policy concerning education and law making.
Sequence of first-time use
The concept of gateway drug is based on observations that the sequence of first-time use of different drugs is not random but shows trends. On the basis of established techniques of longitudinal studies such trends can be described precisely in terms of statistical probability. As to the interpretation of the observed trends, it is important to note the difference between sequence and causation. Both may – but need not – be coupled, a question which is subject of further research, e.g., by physiological experiments.
Examples of trends
From a sample of 6,624 persons who had not used other illegal drugs before their cannabis consumption the overall probability of later use of further illegal drugs was estimated to be 44.7%. Subgroup analyses showed that personal and social conditions, such as gender, age, marital status, mental disorders, family history of substance abuse, Ethnicity, Urbanicity, and educational attainment influenced the height of probability.
In a sample of 27,461 persons who showed no signs of alcohol use disorder (AUD) before their cannabis consumption a second examination three years later revealed a five times higher rate (500%) of AUD compared to a control group that had not consumed cannabis. In another sample of 2,121 persons who already had AUD at the first examination the rate of persistence of AUD three years later was 74% higher in the group of Cannabis consumers than in the group of non-consumers.
A study of drug use of 14,577 US 12th graders showed that alcohol consumption was associated with an increased probability of later use of tobacco, cannabis, and other illegal drugs.
Because a sequence of first-time use can only indicate the possibility – but not the fact – of an underlying causal relation, different theories concerning the observed trends were developed. The scientific discussion (state of 2016) is dominated by two concepts, which appear to cover almost all possible causal connections if appropriately combined. These are the theories of biological alterations in the brain due to an earlier drug use and the theory of similar attitudes across different drugs.
Alterations in the brain
In animals it is relatively simple - compared to humans in clinical studies - to determine if the consumption of a certain drug increases the later attraction of another drug. In rats, cannabis consumption – earlier in life – increased the self-administration of heroin (results based on 11 male rats), morphine (study based on 12 male rats) and also nicotine (34 rats). There were direct indications that the alteration consisted of lasting anatomical changes in the reward system of the brain. The importance of these findings for the reward system in the human brain in relation to the liability to the use of further drugs has been pointed out in several reviews.
In mice nicotine increased the probability of later consumption of cocaine and the experiments permitted concrete conclusions on the underlying molecular biological alteration in the brain. The biological changes in mice correspond to the epidemiological observations in humans that nicotine consumption is coupled to an increased probability of later use of cannabis and cocaine.
According to the concept of similar attitudes across different drugs (common liability to addiction) several personal and environmental factors can lead to a generally increased interest in various drugs. The sequence of first-time use would then depend on the given social and economic conditions. The concept received support from a large-scale genetic analysis that showed a genetic basis for the connection of the prevalence of cigarette smoking and cannabis use during the life of a person.
The results of a twin study presented indications that familial genetic and familial environmental factors do not fully explain these associations, and are possibly only relevant for sequences of some drugs. In 219, same-sex Dutch twin pairs one co-twin had reported cannabis use before the age of 18 whereas the other had not. In the cannabis group the lifetime prevalence of later reported use of party drugs was four times higher and the lifetime prevalence of later reported use of hard drugs was seven times higher than in the non-cannabis group. The authors concluded that at least family influences – both genetic and social ones – could not explain the differences. The study noted that - besides a potential causal role of cannabis use - non shared environment factors could play a role in the association such as differing peer affiliations that preceded the cannabis use. 
While the phrase gateway drug was first popularized by anti-drug activists such as Robert DuPont in the 1980s, the underlying ideas had already been discussed since the 1930s by using the phrases stepping-stone theory, escalation hypothesis, or progression hypothesis.
- Vanyukov MM, Tarter RE, Kirillova GP, et al. (June 2012). "Common liability to addiction and "gateway hypothesis": theoretical, empirical and evolutionary perspective". Drug Alcohol Depend (Review). 123 Suppl 1: S3–17. PMC . PMID 22261179. doi:10.1016/j.drugalcdep.2011.12.018.
- D. B. Kandel (Ed.): Stages and Pathways of Drug Involvement: Examining the Gateway Hypothesis, Cambridge University Press, 2002, ISBN 978-0-521-78969-1, pp. 3-10.
- Secades-Villa, R; Garcia-Rodríguez, O; Jin, C. J.; Wang, S; Blanco, C (2015). "Probability and predictors of the cannabis gateway effect: A national study". International Journal of Drug Policy. 26 (2): 135–142. PMC . PMID 25168081. doi:10.1016/j.drugpo.2014.07.011.
- Weinberger, A. H.; Platt, J; Goodwin, R. D. (2016). "Is cannabis use associated with an increased risk of onset and persistence of alcohol use disorders? A three-year prospective study among adults in the United States". Drug and Alcohol Dependence. 161: 363–7. PMID 26875671. doi:10.1016/j.drugalcdep.2016.01.014.
- Kirby, T; Barry, A. E. (2012). "Alcohol as a gateway drug: A study of US 12th graders" (PDF). Journal of School Health. 82 (8): 371–9. PMID 22712674. doi:10.1111/j.1746-1561.2012.00712.x.
- Morral, A. R.; McCaffrey, D. F.; Paddock, S. M. (2002). "Reassessing the marijuana gateway effect". Addiction (Abingdon, England). 97 (12): 1493–1504. PMID 12472629. doi:10.1046/j.1360-0443.2002.00280.x. (Review).
- Fergusson, D. M.; Boden, J. M.; Horwood, L. J. (2006). "Cannabis use and other illicit drug use: Testing the cannabis gateway hypothesis". Addiction. 101 (4): 556–569. PMID 16548935. doi:10.1111/j.1360-0443.2005.01322.x.
- Ellgren, M; Spano, S. M.; Hurd, Y. L. (2007). "Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats". Neuropsychopharmacology. 32 (3): 607–615. PMID 16823391. doi:10.1038/sj.npp.1301127.
- Cadoni, C; Pisanu, A; Solinas, M; Acquas, E; Di Chiara, G (2001). "Behavioural sensitization after repeated exposure to Delta 9-tetrahydrocannabinol and cross-sensitization with morphine". Psychopharmacology. 158 (3): 259–266. PMID 11713615. doi:10.1007/s002130100875.
- Panlilio, L. V.; Zanettini, C; Barnes, C; Solinas, M; Goldberg, S. R. (2013). "Prior Exposure to THC Increases the Addictive Effects of Nicotine in Rats". Neuropsychopharmacology. 38 (7): 1198–1208. PMC . PMID 23314220. doi:10.1038/npp.2013.16.
- Parsons LH, Hurd YL (2015). "Endocannabinoid signalling in reward and addiction". Nature Reviews. Neuroscience. 16 (10): 579–94. PMC . PMID 26373473. doi:10.1038/nrn4004. (Review).
- Covey DP, Wenzel JM, Cheer JF (2015). "Cannabinoid modulation of drug reward and the implications of marijuana legalization". Brain Research. 1628 (Pt A): 233–43. PMC . PMID 25463025. doi:10.1016/j.brainres.2014.11.034., PDF (Review).
- Renard J, Rushlow WJ, Laviolette SR (2016). "What Can Rats Tell Us about Adolescent Cannabis Exposure? Insights from Preclinical Research". Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 61 (6): 328–34. PMC . PMID 27254841. doi:10.1177/0706743716645288., PDF (Review).
- E. R. Kandel; D. B. Kandel (2014). "A Molecular Basis for Nicotine as a Gateway Drug". New England Journal of Medicine. 371 (10): 932–943. PMC . PMID 25184865. doi:10.1056/NEJMsa1405092.
- Keyes, K. M.; Hamilton, A; Kandel, D. B. (2016). "Birth Cohorts Analysis of Adolescent Cigarette Smoking and Subsequent Marijuana and Cocaine Use". American Journal of Public Health. 106 (6): 1143–9. PMID 27077359. doi:10.2105/AJPH.2016.303128.
- Degenhardt, L; Dierker, L; Chiu, W. T.; Medina-Mora, M. E.; Neumark, Y; Sampson, N; Alonso, J; Angermeyer, M; Anthony, J. C.; Bruffaerts, R; De Girolamo, G; De Graaf, R; Gureje, O; Karam, A. N.; Kostyuchenko, S; Lee, S; Lépine, J. P.; Levinson, D; Nakamura, Y; Posada-Villa, J; Stein, D; Wells, J. E.; Kessler, R. C. (2010). "Evaluating the drug use "gateway" theory using cross-national data: Consistency and associations of the order of initiation of drug use among participants in the WHO World Mental Health Surveys". Drug and Alcohol Dependence. 108 (1–2): 84–97. PMC . PMID 20060657. doi:10.1016/j.drugalcdep.2009.12.001.
- Stringer, S; Minică, C. C.; Verweij, K. J.; Mbarek, H; Bernard, M; Derringer, J; Van Eijk, K. R.; Isen, J. D.; Loukola, A; MacIejewski, D. F.; Mihailov, E; Van Der Most, P. J.; Sánchez-Mora, C; Roos, L; Sherva, R; Walters, R; Ware, J. J.; Abdellaoui, A; Bigdeli, T. B.; Branje, S. J.; Brown, S. A.; Bruinenberg, M; Casas, M; Esko, T; Garcia-Martinez, I; Gordon, S. D.; Harris, J. M.; Hartman, C. A.; Henders, A. K.; et al. (2016). "Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium". Translational Psychiatry. 6 (3): e769. PMC . PMID 27023175. doi:10.1038/tp.2016.36.
- Lynskey, M. T.; Vink, J. M.; Boomsma, D. I. (2006). "Early onset cannabis use and progression to other drug use in a sample of Dutch twins". Behavior Genetics. 36 (2): 195–200. PMID 16402286. doi:10.1007/s10519-005-9023-x., PDF
- Agrawal A, Lynskey MT (2014). "Cannabis controversies: how genetics can inform the study of comorbidity". Addiction (Abingdon, England). 109 (3): 360–70. PMC . PMID 24438181. doi:10.1111/add.12436. (Review).
- D. B. Kandel (Ed.): Stages and Pathways of Drug Involvement: Examining the Gateway Hypothesis, Cambridge University Press, 2002, ISBN 978-0-521-78969-1, p. 4.
- Erich Goode: Marijuana use and the progression to dangarous drugs, in: Miller, Loren, ed. (1974). Marijuana Effects on Human Behavior. Burlington: Elsevier Science. pp. 303–338. ISBN 978-1-4832-5811-9.
- Kandel, D (1975). "Stages in adolescent involvement in drug use". Science. 190 (4217): 912–914. PMID 1188374. doi:10.1126/science.1188374.
- Yamaguchi, K; Kandel, D. B. (1984). "Patterns of drug use from adolescence to young adulthood: II. Sequences of progression". American Journal of Public Health. 74 (7): 668–672. PMC . PMID 6742252. doi:10.2105/ajph.74.7.668.
- Kandel, D; Yamaguchi, K (1993). "From beer to crack: Developmental patterns of drug involvement". American Journal of Public Health. 83 (6): 851–855. PMC . PMID 8498623. doi:10.2105/ajph.83.6.851.
- D. B. Kandel (Ed.): Stages and Pathways of Drug Involvement: Examining the Gateway Hypothesis, Cambridge University Press, 2002, ISBN 978-0-521-78969-1.
- Wayne Hall, Rosalie Liccardo Pacula: Is cannabis a gateway drug? In: Same authors: Cannabis Use and Dependence. Public Health and Public Policy, Cambridge University Press, Cambridge, UK, New York, USA, 2003, ISBN 978-0-521-80024-2, chapt. 10, pp. 104–114.
Lay scientific books
- Mark A.R. Kleiman, Jonathan P. Caulkins, Angela Hawken: Is marijuana a "gateway drug"? In: Same authors: Drugs and Drug Policy. What Everyone Needs to Know, Oxford University Press, 2011, ISBN 978-0-19-983138-8, chapt. 4, question 8, pp. 81–83.
State of research before 1974
- Goode, Erich (1974). "Marijuana use and the progression to dangarous drugs". In Miller, Loren. Marijuana Effects on Human Behavior. Burlington: Elsevier Science. pp. 303–338. ISBN 978-1-4832-5811-9.
- Is marijuana a gateway drug?, website of the National Institute on Drug Abuse at the National Institutes of Health.
- Virginia Gewin: Smoking stokes cocaine cravings: Molecular mechanism found for controversial 'gateway drug' hypothesis, Nature News, November 2, 2011.
- Video: Eric Kandel and Denise Kandel: E-Cigarettes May Promote Illicit Drug Use and Addiction, Columbia University, January 16, 2015.