Testing the cannabis gateway hypothesis in a national sample of Spanish adolescents

Please cite this article as: A. García-Pérez, G. Aonso-Diego, S. Weidberg, R. Secades-Villa, Testing the cannabis
gateway hypothesis in a national sample of Spanish adolescents, Addictive Behaviors Addictive Behaviors (2023),
doi: https://doi.org/10.1016/j.addbeh.2023.107751

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Background. The gateway hypothesis holds that the use of legal substances (i.e.,
tobacco and alcohol) increases the risk of initiating in cannabis use which, in turn, increases
the chances of using other illegal substances. The validity of this hypothesis has been the
subject of intense debate in recent years, finding sequences with a different order.
Moreover, this pattern has been scarcely studied in Spain, where characteristics related to
cannabis use are meaningfully different to other countries. This study aims to examine the
gateway effects of cannabis towards other legal and illegal substances in Spanish
adolescents. Material and methods. Data were obtained from the Ministry of Health in
Spain, through a representative survey of addictive behaviors of 36,984 Spanish
adolescents (Mage=15.7, SD=1.2, 51.4% females). Results. Lifetime cannabis use increased
the likelihood of later legal substance use, both tobacco (OR = 2.0; 95%CI 1.81, 2.22) and
alcohol (OR = 1.93; 95%CI 1.61, 2.31), as well as illegal substances (OR = 5.36; 95%CI
4.80, 5.98) and polysubstance (OR = 18.24; 95%CI 14.63, 22.73). Early age of cannabis
use onset significantly increased the likelihood of subsequent legal and illegal substance
use (ORs between 1.82 and 2.65). Conclusions. These findings confirm and expand the
available evidence on cannabis as a gateway substance. These results can help to drive
preventive strategies for substance use in Spanish adolescents.
Keywords: cannabis, substances, gateway, adolescents, Spanish

In its classical formulation, the gateway hypothesis holds that substance use is
sequenced in different stages (Kandel, 1975, 2003; Kandel et al., 1992, 2006). Specifically,
the initiation of substance use begins with the consumption of alcohol and tobacco,
followed by cannabis use, which in turns, leads to the consumption of other illegal
substances. In this context, cannabis plays an important role since it plays a mediator stage
between the consumption of legal and other drugs. Thus, several studies have concluded
that cannabis use is frequently associated with a significantly increased risk of initiating in
other illegal substances (Choo et al., 2008; Degenhardt et al., 2009; Deza, 2015; Fergusson
et al., 2006, 2015; Fergusson & Horwood, 2000; Jorgensen & Wells, 2021; Lessem et al.,
2006; Taylor et al., 2017; Van Ours, 2003; Wilson et al., 2021), increasing subsequent use
of other illegal substances among 3.5 to 140 times (Fergusson & Horwood, 2000).
Furthermore, these findings are consistent when adjusting for several confounders, such as
socio-economic status, family functioning, personality traits, other drug use, etc.
(Fergusson et al., 2006; Kandel et al., 1986; Lessem et al., 2006).
Despite this evidence, the role of cannabis as a “gateway drug” has been the subject
of intense debate (Jorgensen & Wells, 2021; Melberg et al., 2010; Morral et al., 2002;
Vanyukov et al., 2003, 2012). For instance, Degenhardt et al. (2010) found that this
sequence is altered depending on the context and prevalence of use, in such a way that this
sequence is altered. In this sense, research has recently been conducted that underlines
potential gateway violations, so that in countries with low rates of cannabis use, such as
Japan, most people use other illegal substances before cannabis. Similarly, several studies
have found that a small part of the population use cannabis before other legal substances
(i.e., tobacco and alcohol), and that cannabis use may increase subsequent use of legal
substances (Mayet et al., 2016; Patton et al., 2005; Reed et al., 2021). The reversal of the
classical sequence has important implications in terms of prevention, given that preventive
efforts should be targeted at cannabis use and not just at legal substances. Several
explanations have tried to account for this phenomenon, highlighting biological as well as
psychological factors, such as the common liability model of vulnerability to addictions
(Vanyukov et al., 2003; 2012).
On the other hand, the cannabis gateway hypothesis has been rarely studied outside
the United States. However, it should be noted that although the literature in the European
Union (EU) is scarce, most studies find a cannabis gateway effect (Degenhardt et al., 2010;
Duarte et al., 2000; Lynskey et al., 2006; Mayet et al., 2016; Melberg et al., 2010; Van
Ours, 2003). Degenhardt et al. (2010) clarified that the prevalence of each drug use in a
country might impact on the order of the gateway sequence. Moreover, Melberg et al.
(2010) only found the cannabis gateway effect in a subgroup they called “troubled youths”
(i.e., younger age at onset of substance use, higher rates of substance use and more
interpersonal problems). On the other hand, Lynskey et al. (2006) emphasized that their
results (i.e., cannabis as a gateway drug) are free of familial influences (either genetic or
environmental) by using a twin design. All studies mentioned found that cannabis use
increases the risk of using other substances, although there are several individual and
contextual factors that may mediate these associations. Therefore, the lack of studies in the EU and the complexity of this phenomenon underline the need to study in depth the role of
cannabis as a gateway and the conditions that affect this relationship.
Studying this hypothesis specifically in Spain has scientific and political interest
since the lifetime prevalence of cannabis use in Spain is 37.5%, only below France and
Denmark in the EU (EMCDDA, 2021). Moreover, the two previous studies in the Spanish
population, although they found a cannabis gateway effect, present data from 20 years ago7 (Degenhardt et al., 2010; Duarte et al., 2000), and Spanish lifetime prevalence of cannabis
use has almost doubled in the last 20 years (National Drugs Plan (PNSD), 2022). Finally,
9there is currently an intense political debate on the legalization of the sale and recreational
consumption of cannabis in Spain and other countries of the EU (Proposición de Ley
Integral Del Cannabis, 2021; EMCDDA, 2021). Examining the role of cannabis as a
gateway substance is a crucial step in understanding the etiology of substance use disorders
that would help the development of more effective preventive and treatment interventions.
It would also help policymakers to make correct decisions regarding the legal status of
cannabis use (Aonso-Diego et al., 2022). For example, if cannabis proves to be a clear
gateway to the use of other substances, increasing efforts to restrict cannabis use could be a key strategy to reduce other substance use.18 The objective of this study was three-fold: 1) to describe the sequences of cannabis
use with legal and illegal substances; 2) to estimate the likelihood of using any legal and
illicit drug after cannabis use among a representative national sample of Spanish adolescents, and 3) to analyze the predictive effect of the age of cannabis use onset on
subsequent substance use.

2. Material and method

2.1. Participants and procedure
The current study used data from the Survey on Substance Use in Secondary
Education in Spain (ESTUDES). The inclusion criteria for being eligible to complete this
survey were: a) being between 14 and 18 years old; b) to be studying at 3rd and 4th year of
secondary education (14 – 16 years old), 1st and 2nd year of baccalaureate level (16 – 18
years old), or 1st and 2nd year of basic and intermediate vocational training (16 – 18 years
old); c) to be in the classroom when the survey was conducted. Therefore, those
participants who were not present, who are out of school, or who are 18 years old and are attending university are not included in this survey. This survey is standardized, self-administered, anonymous, and in paper-and-pencil format. The duration of the assessment was between 45 and 60 minutes. Further details of the ESTUDES survey procedures are
available elsewhere (National Drugs Plan (PNSD), 2018b).
A total of 38,010 adolescents completed the survey. The present study used a
subsample of 36,984 adolescents who completed the cannabis prevalence questions.
Sociodemographic and substance use data of the sample is displayed in Table 1. The
sample belonged to 917 educational centers (68.4% public schools), representing the entire
national territory. Before conducting the survey, the school informed the families about the objectives and characteristics of the study. Previously published studies confirm the
suitability of the ESTUDES survey for conducting epidemiological research on adolescent substance use (Alarcó-Rosales et al., 2019; Belzunegui-Eraso et al., 2020; Weidberg et al.,2022).

2.2. Measures
Sociodemographic variables included sex (i.e., man and woman), age, Subjective
Social Status (SSS), nationality, grade repetition, and current level of education (i.e.,
secondary education, baccalaureate, and vocational training). Regarding substance use,
ESTUDES questions included lifetime alcohol, tobacco, cannabis, and other illegal
substance use (i.e., cocaine, amphetamines, methamphetamine, MDMA, heroine, other
non-prescription opioids (e.g., morphine), GHB, LSD, ketamine, magic mushrooms, and
inhalants). An example of the type of drug use prevalence questions used is the following:
Have you ever used heroin? Response options: Yes/No. Age of substance use onset was
determined by asking respondents about the age at which they first used each of the
substances. Illegal polysubstance consisted of lifetime prevalence use of more than one
illegal substance rather than cannabis.

2.3. Data analysis
Odds ratios (ORs) were calculated by dividing the odds of the first groups by the
odds of the second groups. Specifically, the formula is (a / b) / (c / d), where a is the
number of participants who used lifetime cannabis and subsequently used other substances,
b the number of participants who used lifetime cannabis and did not use any other
substances, c the number of participants who did not use lifetime cannabis and used other
substances, and d the number of participants who did not use cannabis nor other substances.
The correspondent 95% confidence interval (95% CI) was calculated for each OR.
A set of binary logistic regressions were conducted to examine the relationship
between age of cannabis use onset and the progression to the use of each of the other
substances (i.e., tobacco, alcohol, illegal substances, and polydrug) from cannabis use.
Additionally, ORs were estimated as a function of sex and SSS. The statistical package
used was SPSS (version 24, Inc., Chicago, IL).

3. Results

3.1. Sequence of cannabis use

Among dual users (i.e., users of cannabis and other substances), it was more common
to use legal substances before cannabis (alcohol 73.2%; tobacco 54.9%), with a small
number of participants starting to use cannabis before these legal substances (alcohol 5.9%,
tobacco 6.7%). On the other hand, it was more frequent for adolescents to start using
cannabis before any other illegal drug (61.1%) than the other way around (10.5%).
There were no differences in these patterns by sex, except for those who started using
cannabis before tobacco, which was higher in males (8.7%) than in females (4.7%). With
respect to SSS, it appears that people with low SSS, compared to adolescents with high SSS, were more likely to initiate cannabis use before alcohol (9.1% vs 6.1%), and less
likely to initiate illicit drug use before cannabis (4.9% vs 15.9%). All this information is
presented in Table S1.
3.2. Probability of using any legal or illicit drug after cannabis use
Figure 1 depicts that the initial use of cannabis duplicated the probability of
subsequent tobacco use. Similarly, the odds of progressing from cannabis to alcohol were
1.93. On the other hand, the likelihood of initiating in at least one illegal drug after
cannabis use was 5.36, while the probability raised to 18.24 in the case of polysubstance use.
There were only sex differences in the likelihood of initiating tobacco use after
cannabis use (ORmale = 2.58 vs ORfemale = 1.77; Wald test = 11.57 [1], p = .001); although
both point in the same direction, the probability was higher in males. No further differences
were found according to sex or SSS. The specific ORs by group can be found in Table S2.
3.3. Age of cannabis use onset and substance use
Early age of cannabis use onset significantly increased the likelihood of progression
from cannabis to other legal and illegal substances (see Table 2). Findings show that
starting to use cannabis one year before nearly doubles the odds of progressing to other
illegal substances, while more than doubles the probabilities of progressing to legal
There were differences only in SSS regarding the odds of progressing to tobacco.
Although all groups pointed in the same direction, adolescents with high SSS were less
likely to progress to tobacco for each year of earlier initiation of cannabis use in
comparison with adolescents with low and medium SSS (ORhigh = 1.75 vs ORmedium = 2.19,
ORlow = 2.55; Wald test = 4.40 [1], p = .030). On the other hand, no further differences
were found according to sex or SSS. The specific ORs by group can be found in Table S3.

4. Discussion
In a large, nationally representative sample of Spanish adolescents, we found that
cannabis use duplicated the probabilities of tobacco and alcohol use and increased more
than five times the likelihood of later use of other illegal drugs. Further, early cannabis use
increased the probability of progression to other, both legal and illegal, substances. Finally,
most of the adolescents followed the classic gateway sequence, using legal substances
before cannabis, and cannabis before illegal substances. These sequences were stable across
both sex and social status.
Our results, in line with previous findings, showed that the use of cannabis increases
the probability of progressing to legal (Agrawal et al., 2006; Badiani et al., 2015; Mayet et
al., 2016; Patton et al., 2005; Ramo et al., 2012; Secades-Villa et al., 2015) and illegal
drugs (Choo et al., 2008; Deza, 2015; Fergusson et al., 2006; Jorgensen & Wells, 2021; Lessem et al., 2006; Taylor et al., 2017; Van Ours, 2003; Wilson et al., 2021). Cannabis use
may precede other legal and illicit drug use because this substance can alter dopamine
levels in the mesolimbic dopamine reward pathway (Agrawal et al., 2004, 2016; R. H.C.
Palmer et al., 2013; Rohan H.C. Palmer et al., 2012; Young et al., 2006) and produce
biochemical changes in the brain that could increase individual responsiveness to other
substances (Ellgren et al., 2007; Leri et al., 2003; Schenk, 2002). Cannabis use can also be
a pleasant experience and reduce the discomfort of cannabis users, and these reinforcing
subjective feelings can be generalized and trigger other substance use (Baggio et al., 2015;
Fergusson et al., 2003, 2006; Fergusson & Horwood, 1997). This mechanism fits with the
findings from Secades-Villa et al. (2015), since the classical gateway hypothesis is more
intense in individuals with psychopathological disorders, where substance use produces
stronger positive and negative reinforcement. In addition, cannabis use produces negative
affect (Dorard et al., 2008), which in turn can increase the likelihood of initiating other
drugs to cope with these problems (Hurd et al., 2014). Finally, cannabis users are exposed
to a social context that influences both favorable attitudes towards other substance use and
its availability, since both the distribution channels of cannabis and the places where
cannabis is smoked frequently overlaps with the distribution and consumption context of
other substances (Agrawal et al., 2008; Dishion & Owen, 2002; Fergusson et al., 2006;
Fergusson & Horwood, 1997; Kuntsche, 2004; Mayet et al., 2010; Patton et al., 2005;
Wagner & Anthony, 2002).
Our results are compatible with the common liability theory (Mayet et al., 2016;
Morral et al., 2002; Van Leeuwen et al., 2011; Vanyukov et al., 2012) describe that
variation in liability to drug use can be explained by common genetic and individual factors
that increase the risk of multiple substance use, regardless of the order of initiation. For
example, some externalized transdiagnostic factors such as impulsivity, non-compliance
with rules or aggressiveness have been related to substance use in general (Eaton et al.,
2015); while other factors such as abnormal perception of reality, hopelessness, anxiety, depression, and suicide attempts were associated with cannabis use in particular (Moreno-
Mansilla et al., 2021). In any case, at the clinical level, this perspective highlights the importance of focusing on the application of interventions that modify transdiagnostic
variables that transcend the use of specific substances (Kim & Hodgins, 2018).
We also found that early cannabis use increases the likelihood of progressing to both
legal (Agrawal et al., 2006; Kokkevi et al., 2006; Mayet et al., 2016; Scholes-Balog et al.,
2016) and illegal substances (Agrawal et al., 2004; Fergusson et al., 2006; Gundy &
Rebellon, 2010; Lynskey et al., 2006; Morral et al., 2002; Secades-Villa et al., 2015). This
finding can be explained by the same mechanisms detailed above (e.g., common liability),
although it is important to emphasize that early access to the contexts where cannabis is
obtained contributes to early initiation of other substances that are acquired in the same
context. In addition, one possibility, given the age range of our sample (i.e., 14-18 years), is
that an early onset of cannabis use is related not to a higher lifetime risk of illicit substance
use, but to an earlier onset of such use (Lynskey et al., 2006).
In the current sample, most people followed the classic gateway sequence. Only a few
adolescents used cannabis before legal substances (6%), and illegal substances before
cannabis (10%). These results are consistent with the study by Degenhardt et al. (2010), such that in countries with a high prevalence of cannabis use, as is the case of Spain (30%
lifetime in adolescents), the percentage of cannabis gateway violations is low. However,
although there is not a high percentage of cannabis gateway violations, this percentage seems to have increased as the prevalence of cannabis use in Spain has increased (Aonso-Diego et al., 2022). Changes in other factors such as attitudes and the availability/accessibility of each substance may have affected the substance use sequences.
The different hypotheses on the explanatory mechanisms of the gateway hypothesis
imply different legal and preventive actions (Fergusson et al., 2006). While biological and
behavioral factors encourage the restriction of cannabis use, environmental factors would
point to cannabis legalization for recreational use in order to remove cannabis from the
context in which other illegal substances are obtained. Nevertheless, the legalization of
cannabis for recreational use implies a decrease in their risk perception and greater
accessibility and availability, and this could lead to an increase in cannabis use (Budney &
Borodovsky, 2017; Isorna et al., 2022; Mennis et al., 2023; Sandhu et al., 2019). Another
way is to harden legal regulation, since it could be closely associated with a reduction in
cannabis demand by increasing its cost (Collins et al., 2014), understood comprehensively,
in terms of economic, social, and time costs. Actions undertaken in this way will probably
decrease both legal and illegal substance use. In any case, the fact that cannabis use
increases the probability of consuming legal substances, but to a lesser extent than illegal
substances, suggests that both individual and contextual factors act on the observed results.
Interventions should therefore take into account both lines of action. In addition, preventive
actions should focus on delaying the age of initiation of cannabis use, since this would
reduce the probability of initiation in other substances.
In the Spanish context, there are some specific preventive recommendations that
should be highlighted. In Spain, there is a very low perceived risk for cannabis use (47.8%
of adolescents believe that occasional cannabis use implies few or no health problems), and
they also perceive high accessibility to cannabis, as 61.1% believe that they could obtain
cannabis easily or very easily (PNSD, 2022). In this sense, both educational campaigns
(aimed at increasing the perceived risk for cannabis use, denormalizing cannabis use, and
providing healthy leisure time alternatives that can compete with drug use) and
environmental actions (increasing control over cannabis trafficking, increasing control and
sanctions of cannabis use on public roads -cannabis use is legal in Spain at a private level-,
controlling the sale and consumption of cannabis in nightlife spaces, or regulating the sale
and advertising of cannabis products that do not contain THC) may be developed in order
to reduce cannabis use and, therefore, the subsequent use of other substances (Becoña,
2021; PNSD, 2018a).
This study is not exempt of limitations common to most large-scale surveys. First,
this is a cross-sectional study, so no causal conclusions can be obtained. Second, those
adolescents who initiated in cannabis use at the same time as other legal and illegal
substances were excluded from the analysis. Third, our study was based on retrospective
reports, which may be subject to recall bias. Finally, those individuals who dropped-out
educational system are not included, which could alter the results found.

3 5. Conclusions

Despite the previous limitations, this study expands the available evidence on
cannabis as a double gateway drug, finding that cannabis use markedly increases the
likelihood of subsequently using other legal and illegal substances. We hope these findings
can be helpful for the development of preventive and treatment interventions in Spain.

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Table 1
Characteristics of the sample
Variables Total Sample (n = 36,984) Demographics
Age (years) a 15.7 ± 1.2
Sex (% women) 51.6 (19,055)
Nationality (% Spanish) 90.6 (33,511)

Subjective Social Status
Low 4.1 (1,487)
Medium 82.4 (30,110)
High 13.5 (4,930)
Education level Secondary education 55.8 (20,625)
Baccalaureate course 36.6 (13,542)
Vocational training 7.6 (2,817)
Grade repetition 22.8 (8,398)
Drug use Lifetime prevalence
Tobacco 39.3 (14,500)
Alcohol 76.4 (28,251)
Cannabis 29.2 (10,816)
Other illegal substances 7.3 (2,707)
Other illegal polysubstance 3.6 (1,318)
Age of onset
Tobacco 14.2 ± 1.6Alcohol 14.0 ± 1.5 Cannabis 14.9 ± 1.4

Other illegal substances 14.8 ± 2.1
Note.a mean ± standard deviation; b% (n)

Table 2
Relationship between age of cannabis use onset and subsequent substance use

B OR 95%CI

Tobacco .753 2.124 1.940, 2.325
Alcohol .979 2.663 2.191, 3.236
Illegal substance .616 1.851 1.757, 1.949
Illegal polysubstance .601 1.824 1.723, 1.931

Note. OR = odds ratio; CI = confidence interval.

Table S1
Use patterns among adolescents who use cannabis


Variables N (%) Male Female Low Medium High

Tobacco users (n = 8909)
Cannabis ->Tobacco 593 (6.7%) 378 (8.7%) 215 (4.7%) 28 (6.5%) 458 (6.5%) 98 (7.4%)
Tobacco -> Cannabis 4,889 (54.9%) 2,160 (49.8%) 2,729 (59.7%) 227 (52.7%) 3,872 (54.6%) 761 (57.5%)
Alcohol users (n = 7321)
Cannabis -> Alcohol 594 (5.9%) 380 (7.4%) 214 (4.4%) 44 (9.1%) 452 (5.7%) 91 (6.1%)
Alcohol -> Cannabis 7,321 (73.2%) 3,600 (70.5%) 3,721 (76.0%) 313 (64.4%) 5,874 (73.9%) 1,082 (72.8%)
Illegal substance users (n = 1539)
Cannabis -> Illegal substance 941 (61.1%) 572 (61.7%) 369 (60.3%) 77 (74.8%) 691 (61.3%) 164 (55.6%)

Illegal substance -> Cannabis 162 (10.5%) 97 (10.5%) 65 (10.6%) 5 (4.9%) 107 (9.5%) 47 (15.9%)
Polysubstance users (n = 779)
Cannabis ->Polysubstance 617 (79.2%) 385 (79.9%) 232 (78.1%) 54 (91.5%) 438 (80.4%) 119 (71.7%)
Polysubstance -> Cannabis 162 (20.8%) 97 (20.1%) 65 (21.9%) 5 (8.5%) 107 (19.6%) 47 (28.3%)
Note. SSS = subjective social status.

Author disclosures

Role of funding sources
This research was supported by a Predoctoral Grant from the National Agency of
Research of the Spanish Ministry of Science, Innovation, and Universities (FPU17/00659).
Spanish Ministry of Science, Innovation, and Universities had no role in the study design,
collection, analysis, or interpretation of the data, writing the manuscript, or the decision to
submit the paper for publication.
Ángel García-Pérez: conceptualization, formal analysis, writing – original draft. Gema
Aonso-Diego: formal analysis, writing – original draft. Sara Weidberg: formal analysis,
writing – review & editing. Roberto Secades-Villa: conceptualization, writing – review &
Declaration of Competing Interest
The authors have no conflicts of interest to declare.
The authors thank the Spanish National Drug Plan (Ministry of Health, Social Services
and Equality) for providing the survey data.

Declaration of Competing Interest
The authors have no conflicts of interest to declare.

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