Drug and Alcohol Dependence 236 (2022) 109476

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Drug and Alcohol Dependence

journal homepage: www.elsevier.com/locate/drugalcdep

A Bayesian learning model to predict the risk for cannabis use disorder
Rajapaksha Mudalige Dhanushka S. Rajapaksha a, Francesca Filbey b, Swati Biswas a, *,
Pankaj Choudhary a, *
a
Department of Mathematical Sciences, University of Texas at Dallas, Richardson, TX, USA
b
School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA

A R T I C L E I N F O A B S T R A C T

Keywords: Background: The prevalence of cannabis use disorder (CUD) has been increasing recently and is expected to
Cannabis use disorder increase further due to the rising trend of cannabis legalization. To help stem this public health concern, a model
Prediction model is needed that predicts for an adolescent or young adult cannabis user their personalized risk of developing CUD
Bayesian methods
in adulthood. However, there exists no such model that is built using nationally representative longitudinal data.
Machine learning
Methods: We use a novel Bayesian learning approach and data from Add Health (n = 8712), a nationally
Model validation
representative longitudinal study, to build logistic regression models using four different regularization priors:
lasso, ridge, horseshoe, and t. The models are compared by their prediction performance on unseen data via 5-
fold-cross-validation (CV). We assess model discrimination using the area under the curve (AUC) and calibration
by comparing the expected (E) and observed (O) number of CUD cases. We also externally validate the final
model on independent test data from Add Health (n = 570).
Results: Our final model is based on lasso prior and has seven predictors: biological sex; scores on personality
traits of neuroticism, openness, and conscientiousness; and measures of adverse childhood experiences, de­
linquency, and peer cannabis use. It has good discrimination and calibration performance as reflected by its
respective AUC and E/O of 0.69 and 0.95 based on 5-fold CV and 0.71 and 1.10 on validation data.
Conclusion: This externally validated model may help in identifying adolescent or young adult cannabis users at
high risk of developing CUD in adulthood.

1. Introduction Statistical Manual of Mental Disorders (DSM-IV) (Marel et al., 2019).

Substance use disorders (SUDs) constitute a serious public health
issue in the US (SAMHSA, 2016). In 2019, among persons aged 12 or
older, 20.4 million (7.4%) met the clinical diagnostic criteria for a past
year SUD of alcohol or any illicit drugs (SAMHSA, 2020). Cannabis is the
most commonly used illicit substance in the world (NIDA, 2019). In the
US, several states have legalized medical and/or recreational use of
cannabis (Bridgeman and Abazia, 2017; Hasin et al., 2017). These new
regulations may be partly responsible for a recent increase in cannabis
use and its adverse consequences (NCDAS, 2018).
Cannabis use among adolescents and young adults has also increased
in recent years (Schulenberg et al., 2021). In 2019, 43% of college stu­
dents consumed cannabis, which was the highest rate of cannabis con­
sumption in that group since 1983 (NCDAS, 2018). It is estimated that
around 34% of cannabis users develop cannabis use disorder (CUD)
during their lifetime based on the 4th edition of the Diagnostic and
Another study using DSM-5 criteria found that the lifetime probability of
transition from cannabis use to CUD is 27% (Feingold et al., 2020).
Furthermore, people who use cannabis are more likely to be poly­
substance users (NCDAS, 2018). Given that SUD is a chronic brain dis­
order associated with long-term, negative consequences (Heilig et al.,
2021), the need to identify adolescent and young adult substance users
who are at risk of developing CUD/SUD in future has become more
important than ever.
Several risk factors are known to be associated with substance use
and SUDs in general and CUD in particular. These include male sex,
substance initiation at an early age, early exposure to traumatic events,
family and peer substance use, mood related risk factors such as
depression and anxiety, personality traits such as impulsivity, conduct
disorder symptoms such as delinquent behavior, and attention deficit
hyperactivity disorder (ADHD) (Beaton et al., 2014; Douglas et al., 2010;
Gray and Squeglia, 2018; Ketcherside et al., 2016; Koh et al., 2017; Lowe

* Correspondence to: 800 W Campbell Rd, FO 35, Richardson, TX 75025, USA.

E-mail addresses: swati.biswas@utdallas.edu (S. Biswas), pankaj@utdallas.edu (P. Choudhary).

https://doi.org/10.1016/j.drugalcdep.2022.109476
Received 28 December 2021; Received in revised form 19 April 2022; Accepted 23 April 2022
Available online 29 April 2022
0376-8716/© 2022 Elsevier B.V. All rights reserved.
R.M.D.S. Rajapaksha et al.
et al., 2020; Meier et al., 2016; Rajapaksha et al., 2020; Tomko et al.,
2019; Verdejo-García et al., 2008; Zhang-James et al., 2020).
With a vast literature available on risk factors for SUD, a natural and
practically important next step is to build risk prediction models for
SUD. Indeed, such models have been developed for several diseases and
disorders, including depression, ADHD, and mental illness (Bernardini
et al., 2017; Cattelani et al., 2019; Caye et al., 2019; Chowdhury et al.,
2018; D’Agostino et al., 2008; Gail et al., 1989). Although some studies
have developed simple cumulative risk indices and/or risk scores for
SUD outcomes (Hayatbakhsh et al., 2009; Meier et al., 2016), efforts to
build risk prediction models to predict an SUD outcome are a recent
development. Rajapaksha et al. (2020) proposed a preliminary model
for predicting CUD by applying statistical and machine learning (ML)
techniques. Another recent study applied ML techniques to a longitu­
dinal dataset and predicted SUD (Jing et al., 2020). A few other studies
also used ML techniques to predict substance use outcomes (Hu et al.,
2020; Nasir et al., 2021; Zhang-James et al., 2020; Zoboroski et al.,
2021).
However, all these studies have a common and major limitation of
being based on data from a limited geographic location or high-risk
population (Hayatbakhsh et al., 2009; Hu et al., 2020; Jing et al.,
2020; Nasir et al., 2021; Rajapaksha et al., 2020; Zhang-James et al.,
2020). Therefore, these models are not generalizable to a larger or
nationwide population of substance users and thus may not be suitable
for risk assessment in clinical practice. Moreover, some studies have
focused only on certain specific types of predictors rather than consid­
ering a comprehensive set of risk factors and hence are not suitable for
risk prediction as such. Another crucial aspect of any risk prediction
model is the use of longitudinal data so that one can ensure that the risk
factors have been measured before the development of the outcome
rather their measurements being effects of the outcome. Although some
studies used longitudinal data, they did not consider the effect of the
longitudinal trajectory of risk factors and used their cross-sectional
summaries (Hayatbakhsh et al., 2009; Hu et al., 2020; Jing et al.,
2020; Meier et al., 2016). Finally, and perhaps most importantly, none
of these tools has been independently validated on external data.
Given the large number of potential risk factors for SUD, for practical
utility it is important to ensure that a risk prediction model is parsi­
monious. This may be achieved using regularization methods as they
shrink (penalize) regression coefficients towards zero, thereby avoiding
overfitting and improving prediction accuracy on future unseen data
(Park and Casella, 2008; Tibshirani, 1996, 2011). Regularization is
accomplished by adding a penalty term to the negative log-likelihood
function that we need to minimize to fit a model. For example, the
penalty term under lasso (ridge) regularization is the sum of absolute
values (squares) of the slope coefficients multiplied by a non-negative
penalty parameter. This parameter is chosen optimally through
cross-validation.
Such regularization can be achieved through Bayesian learning
methods in a more flexible way. In classical framework, the penalty
parameter has to be estimated separately from the regression co­
efficients. While in Bayesian framework, the penalty parameter is part of
the whole model, which contains not only the regression coefficients but
other parameters as well (e.g., variance parameters). All parameters
have priors (e.g., in Bayesian lasso, regression coefficients have Laplace
priors) and thus regularization takes place within the model building
process in an integrated manner (Van Erp et al., 2019). Furthermore,
Bayesian regularization methods naturally quantify the uncertainty in
estimates through posterior distributions, which is not so straightfor­
ward for their classical counterparts (Carvalho et al., 2010; O’Hara and
Sillanpaa, 2009; Park and Casella, 2008; Van Erp et al., 2019). Despite
these advantages, there is no study in the SUD literature that has used
Bayesian learning methods for risk prediction.
In this study, we built Bayesian risk prediction models to predict the
risk of developing CUD in adulthood based on risk factors (which may
vary over time) measured in adolescence and young adulthood. We used
2
Drug and Alcohol Dependence 236 (2022) 109476
nationally representative longitudinal data from National Longitudinal
Study on Adolescent Health (Add Health) (Harris et al., 2009). A
comprehensive set of potential predictors, including demographic,
behavioral, personality, and cognitive characteristics of individuals, was
considered. The final model was independently validated on an external
test data, also obtained from Add Health. This study has been approved
by the Institutional Review Board of the University of Texas at Dallas.
2. Methods
2.1. Participants
Add Health used a multistage stratified cluster sampling design to
ensure that the sample reflected the adolescent population of the United
States in terms of urbanicity, region, school size, school type (public/
private), and ethnicity (Harris et al., 2009). Adolescents were first
enrolled when they were in grades 7–12 during the 1994–95 school year
(wave I). They were followed up in 1996 (wave II), 2001–2002 (wave
III), and 2008 (wave IV). The most recent wave (wave V) was in
2016–18, however, information regarding SUDs was not collected in this
wave. So, we used data up to wave IV during which the participants were
adults aged 24–32.
2.2. Data preparation
Our response variable is a binary measure of lifetime diagnosis of
CUD, which was measured only in wave IV. For model building, we
included only those participants who started using cannabis during any
of the first three waves, participated in wave IV, and have survey
weights available. Diagnosis of CUD was derived from Add Health items
that were originally based on DSM-IV for lifetime diagnosis of cannabis
use dependence. Specifically, each item had dichotomous (Yes/No) re­
sponses indicating whether or not one engaged in a certain substance
dependence behavior corresponding to each of the diagnostic criteria
outlined in DSM-IV for cannabis dependence, such as tolerance, with­
drawal, etc. An answer of “yes” to three or more questions within a 12-
month period was indicative of CUD. This is a widely used criterion to
measure CUD (Feingold et al., 2020). Potential participants were
excluded if they developed CUD but did not provide an age of CUD onset
or had inconsistency between their reported status of ever use cannabis
and age of first cannabis use across different waves. There were 9491
participants after applying these inclusion and exclusion criteria.
Add Health administered several age-specific questionnaires con­
taining more than 1000 items. We constructed around 50 potential
predictors from these questionnaires based on literature review. Some
predictors were cross-sectional, measured in a single wave, while the
others were longitudinal, measured across multiple waves. We consid­
ered two ways of summarizing longitudinal predictors for inclusion in
the CUD model: (1) using random effects obtained by fitting a separate
linear mixed effects model (LMM) for each predictor relating the pre­
dictor to age of participants at different waves (see Supplementary
Materials), and (2) taking the average/maximum exposure over
different waves (Chen et al., 2015; Dandis et al., 2020).
2.3. Initial variable processing
While most of the predictors came from waves I to III, the following
two types came from wave IV. One retrospectively measured adverse
childhood experiences (ACEs), which occurred before age 18 and were
used to create the ACE scale. The other measured personality traits that
are believed to remain relatively stable over time (Caspi et al., 2005;
Damian et al., 2019). Further, although CUD was measured in wave IV, a
person could have developed CUD for the first time before wave IV.
Hence, for each CUD case, we only considered the portion of their data
that were recorded before their age of CUD onset. Thus, it was effec­
tively ensured that all predictors were measured before the outcome.
R.M.D.S. Rajapaksha et al.
Some predictors had substantial missing data. Therefore, an initial
variable filtering process was implemented to identify potentially
important predictors while maximizing the number of participants with
complete data. As complex survey design must be accounted for even in
this initial variable filtering, we fitted survey multiple logistic regression
models using varying sample sizes (corresponding to different pro­
portions of missing values) and considered a variable to be potentially
important if its p-value was less than 0.3 in at least one of the models.
This process identified 15 predictors (see Table 1) and 8712 participants
with complete data on them. All quantitative predictors were scaled/
transformed to lie within [0,1] by diving by their maximum possible
value (all except TV hours) or their maximum value observed in the data
(TV hours). This helps in ensuring portability of the model to data
wherein predictors are measured in different scales. This final data set is
used as the training data.
2.4. Statistical methods
2.4.1. Variable selection and Bayesian learning models
We used a Bayesian learning approach within the framework of lo­
gistic regression models with random effects. This involves specifying
priors for the unknown model parameters. The priors on regression
coefficients serve to regularize them (Gelman et al., 2014). We used four
different regularization priors: lasso, ridge, horseshoe, and t (Van Erp
et al., 2019). All models incorporated the complex survey sampling
design by weighting each participant’s data with their survey weight in
the likelihood and including the stratification variable region as a fixed
covariate and the clustering variable school as a random effect (see
Supplementary Materials for details).
As priors for regression coefficients are continuous, they do not
automatically provide variable selection. Therefore, we used two
methods for variable selection after fitting the full models with 15 pre­
dictors: credible interval and probability thresholding (Li and Lin, 2010;
Van Erp et al., 2019). Briefly, in the first method, a predictor is selected if
a credible interval for its regression coefficient excludes 0. The level of
the interval is varied, e.g., 70%, 80%, 95%, etc. As the level increases,
the interval becomes wider, it includes 0 more often, and hence fewer
Table 1
Summary of predictors that passed initial variable filtering.
Predictor Description
Biological sex 0 =Female, 1 =Male
Race 1 =White, 2 = Black/African American, 3 = American
Indian/Native American, 4 =Asian, 5 =other
ACE scale Number of adverse childhood experiences that occurred
before age 18.
Neuroticism scale Measure of general tendency to experience negative
feelings. A higher value implies a greater tendency.
Conscientiousness scale Measure of forward planning, organization, and ability to
carry out tasks. A higher value implies greater
conscientiousness.
Agreeableness scale Measure of compassion, eagerness to cooperate, and
tendency to avoid conflict. A higher value implies more
agreeableness.
Openness scale Measure of openness to new experiences and
imaginativeness. A higher value implies more openness.
Anxiety scale Number of times experienced anxiety symptoms.
Depression scale Number of times experienced depression symptoms.
Delinquency scale Number of times involved in delinquent activities. A
higher value implies a greater involvement.
Violence victimization Number of times experienced violent incidents.
scale
Peer alcohol use Number of best friends (out of 3 best friends) who drink
alcohol at least once a month.
Peer cannabis use Number of best friends (out of 3 best friends) who use
cannabis at least once a month.
Peer smoking Number of best friends (out of 3 best friends) who smoke
at least 1 cigarette a day.
TV hours Number of hours per week watched television.
3
Drug and Alcohol Dependence 236 (2022) 109476
predictors are selected. The second method excludes a variable if the
posterior probability that its regression coefficient is within ± 1 poste­
rior standard deviation (SD) of 0 exceeds a certain threshold. The
threshold is varied such as 0.3, 0.4, 0.5, etc. A higher threshold leads to
fewer variables meeting the exclusion requirement and hence to fewer
excluded variables. By applying these variable selection methods with
different levels/thresholds and different regularization priors, we ob­
tained a total of 40 competing models. Each model provides a predicted
probability of CUD for an individual (see Supplementary Materials for its
calculation).
2.4.2. Using prediction accuracy to obtain the best model
To identify the best among the competing models, we compared their
prediction accuracy on unseen data via 5-fold cross-validation (CV)
(James et al., 2013) and Bayesian leave one out (LOO) cross-validation
(Vehtari et al., 2017). These approaches provide a good assessment of
model performance on unseen data by protecting against overfitting.
The model discrimination is assessed by area under the receiver oper­
ating characteristic curve (AUC) based on 5-fold CV and the Bayesian
LOO estimate. Higher AUC and LOO indicate better prediction accuracy.
To evaluate model calibration, we compared the expected number of
cases (E) based on 5-fold CV with the observed (O) number of cases. The
closer the E/O value is to 1, the better is the model performance.
2.4.3. External validation
To externally validate the final proposed model, we utilized an in­
dependent test dataset. It consisted of Add Health participants whose
survey weights were missing and hence were not included in the training
data. We calculated their risk of developing CUD using the final model
and compared with their actual CUD status. Then we calculated AUC
and E/O.
More information about statistical methods is available in Supple­
mentary Materials. The models were fitted using the statistical software
system R (R Core Team, 2019) with the following packages: RStan (Stan
Development Team, 2020) for Bayesian inference, lme4 (Bates et al.,
2015) to summarize longitudinal predictors using random effects, sur­
vey (Lumley, 2004) for initial variable filtering, loo for cross-validation
(Vehtari et al., 2020), and pROC (Robin et al., 2011) for AUC.
3. Results
3.1. Sample characteristics
In our final dataset (n = 8712), the unweighted and weighted
prevalence of lifetime CUD are 7.51% and 7.84%, respectively. As seen
in Table 2, compared to controls (i.e., the non-CUD participants), the
cases are more likely to be males (61% vs 50%); and on average expe­
rienced more ACEs (0.29 vs 0.25) and reported higher neuroticism (0.56
vs 0.52) and openness (0.76 vs 0.73) but lower conscientiousness (0.70
vs 0.73). Table 3 presents sample characteristics for longitudinal pre­
dictors across the waves in which they were measured. Generally,
depressive symptoms, peer alcohol use, peer cannabis use, and peer
smoking increased over time while delinquent activities and violence
victimization decreased. For all the predictors, the average score of a
predictor was at least as high for cases as for controls.
3.2. Results from Bayesian learning models
As described in the Methods section, we applied four shrinkage
priors and performed variable selection among 15 predictors that passed
the initial filtering using credible interval and thresholding methods.
Interestingly, the model with highest prediction accuracy for each prior
contained the same seven predictors: biological sex, ACE, conscien­
tiousness, neuroticism, openness, delinquency, and peer cannabis use.
Next, we fitted models with the same priors but with data on only these
seven predictors, resulting in a slightly larger sample size of 8753 due to
R.M.D.S. Rajapaksha et al. Drug and Alcohol Dependence 236 (2022) 109476

Table 2 neuroticism and openness, lower conscientiousness, and larger propor­

Summary of cross-sectional predictors: percentage for categorical predictors and tion of friends using cannabis. The AUC of this model was 0.69 and its E/
mean (standard deviation) for continuous predictors. The p-values are based on O was 0.953. These indicate good discrimination ability and calibration
chi-square test of association in case of categorical predictors and on univariate performance of the model.
logistic regression models in case of continuous predictors.
Predictor Total (n = Cases (n Controls (n = p-
8712) = 654) 8058) value 3.3. External validation results
Biological sex 0.001
Male % 50.85 61.16 50.01 Next, we applied the final model to the independent validation
Female % 49.15 38.84 49.99 dataset (n = 570). The prevalence of lifetime CUD in this sample was
7.19%, comparable to 7.51% in the training data. The AUC was 0.71 and
Race 0.507 the E/O was 1.10. Thus, although the model slightly overpredicted the
White % 70.14 71.87 70
Black/ African American % 20.14 20.34 20.13
number of cases, its discrimination ability was good, and it was well
American Indian/ Native 2.03 1.99 2.04 calibrated. Table 6 shows the E/O for the five risk quintile groups, two
American % levels of biological sex, and the groups obtained using median as cutoff
Asian % 5.75 4.13 5.88 for each risk factor. We see that the E/O value is quite close to 1 for the
Other % 1.93 1.68 1.95
two highest risk quintile groups, male sex, below median neuroticism,
ACE scale 0.25 0.29 0.25 (0.19) 0.001
(0.19) (0.20) above median openness, and all delinquency, conscientiousness, and
Neuroticism scale 0.53 0.56 0.52 (0.14) < ACE groups, indicating that the model performed very well for these
(0.14) (0.14) 0.001 groups. For the remaining groups also, the E/O generally does not
Conscientiousness scale 0.73 0.70 0.73 (0.14) < deviate too far from 1 (except the risk quintile group 3 consisting of
(0.14) (0.14) 0.001
Agreeableness scale 0.76 0.76 0.76 (0.12) 0.876
moderate risk individuals).
(0.12) (0.12)
Openness scale 0.73 0.76 0.73 (0.12) 0.001 4. Discussion
(0.12) (0.13)
TV hours 0.16 0.17 0.16 (0.15) 0.229
(0.15) (0.15)
Substance use disorders constitute a growing public health problem
in the US, incurring enormous societal costs (NIDA, 2017, 2019; WHO,
2020). Increasing legalization of cannabis usage is likely to exacerbate
fewer missing observations. this trend. Thus, there is an urgent need to develop prediction models to
As delinquency and peer cannabis use are longitudinal predictors, we identify adolescents and young adults who are at high risk of developing
explored the possibility of including them in the model simply as CUD in future so that early intervention and preventive measures may
average or maximum over the waves in which they were measured be provided. In this study, we built such a model using nationally
rather than as random effects. We found that the average provided better representative longitudinal data. To our knowledge, this is the first such
prediction performance for delinquency (Table 4). As average is also risk prediction model for any SUD. This model was obtained by applying
simpler for practical implementation, we use it in the final model. On the state-of-the-art regularization methods under the framework of Bayesian
other hand, for peer cannabis use, the random effect provided better learning. It uses only seven predictors and validated well on external test
performance and hence was retained. Next, as the model performance data. For comparison, we also tried unregularized Bayesian models, but
was practically identical for all four priors (see Table 4), we chose the they had larger number of predictors and lower prediction accuracy than
lasso model because it is the most popular among the models considered. the proposed model.
Lastly, the stratification variable region was dropped from the final The risk factors identified in our model are consistent with the
model as it did not increase prediction accuracy and the simpler model is
easier to use in practice. Table 4
The results of our final model are presented in Table 5. It shows Comparison of prediction performance of Bayesian learning models using the
posterior means of regression coefficients (β) and odds ratios (OR) for random effects (RE) and average for delinquency scale.
predictors in the model and their 95% credible intervals. For continuous Model AUC E/O LOO
cross-sectional predictors in the model, which are scaled to lie between
Lasso model RE for delinquency 0.66 0.952 -2233.5
0 and 1, it also shows posterior means and 95% credible intervals for
average for delinquency 0.69 0.953 -2192.4
odds ratios on original scale (OR*), which are given by exp(β/M), where Ridge model RE for delinquency 0.66 0.950 -2233.9
M is the maximum possible value for the predictor (used for scaling). For average for delinquency 0.69 0.952 -2192.5
a longitudinal predictor, obtaining odds ratio on the original scale is not t model RE for delinquency 0.66 0.951 -2233.5
straightforward as its maximum possible value varies across waves. A average for delinquency 0.69 0.952 -2192.4
Horseshoe model RE for delinquency 0.66 0.952 -2233.7
higher likelihood of CUD was associated with male sex, greater adverse average for delinquency 0.69 0.955 -2192.8
childhood experiences and involvement in delinquent activities, higher

Table 3
Summary of longitudinal predictors: Mean (standard deviation) across different waves. The p-values are based on a logistic regression model with SUD status as
response and random effects associated with the longitudinal predictor as covariates.
Wave 1 Wave 2 Wave 3

Variable Overall Cases Controls Overall Cases Controls Overall Cases Controls p-value

Anxiety scale 0.15 (0.10) 0.16 (0.11) 0.15 (0.10) 0.15 (0.10) 0.16 (0.10) 0.15 (0.100 0.006
Depression scale 0.27 (0.09) 0.29 (0.10) 0.27 (0.09) 0.28 (0.09) 0.28 (0.09) 0.28 (0.09) 0.30 (0.11) 0.33 (0.11) 0.30 (0.11) 0.008
Delinquency scale 0.12 (0.13) 0.16 (0.14) 0.12 (0.13) 0.09 (0.11) 0.12 (0.13) 0.08 (0.11) 0.03 (0.06) 0.05 (0.07) 0.03 (0.06) < 0.001
Violence victimization scale 0.05 (0.07) 0.06 (0.08) 0.05 (0.07) 0.02 (0.06) 0.03 (0.07) 0.02 (0.06) 0.02 (0.06) 0.02 (0.06) 0.02 (0.05) 0.002
Peer alcohol use 0.45 (0.40) 0.48 (0.41) 0.45 (0.40) 0.47 (0.40) 0.47 (0.40) 0.46 (0.40) 0.66 (0.39) 0.72 (0.36) 0.65 (0.39) 0.01
Peer cannabis use 0.28 (0.36) 0.34 (0.39) 0.28 (0.36) 0.33 (0.37) 0.4 (0.40) 0.32 (0.37) <0.001
Peer smoking 0.34 (0.38) 0.36 (0.39) 0.33 (0.37) 0.37 (0.39) 0.42 (0.40) 0.37 (0.39) <0.001

4
R.M.D.S. Rajapaksha et al. Drug and Alcohol Dependence 236 (2022) 109476

Table 5
Final Bayesian learning model using lasso prior: Posterior means of regression coefficients, posterior means of odds ratios (OR), 95% credible intervals for OR, posterior
means of odds ratio (OR*) on original scale (only for continuous cross-sectional variables), and 95% credible intervals for OR* .
Variable Posterior mean of coefficient Posterior mean of OR Credible Interval for OR Posterior mean for OR* Credible interval for OR*

Intercept -4.68
Biological sex 0.33 1.40 (1.17,1.66)
ACE scale 0.51 1.71 (1.08,2.56) 1.06 (1.01,1.11)
Conscientiousness scale -1.14 0.34 (0.17,0.58) 0.94 (0.92,0.97)
Neuroticism scale 1.72 5.86 (3.01,10.49) 1.09 (1.06,1.12)
Openness scale 1.68 5.71 (2.66,10.89) 1.09 (1.05,1.13)
Delinquency scale 3.84 50.07 (22.43,98.38)
Peer cannabis use 0.67 2.01 (1.24,3.06)

socioeconomic position during childhood (Walsh et al., 2019). Our final

Table 6
model contained the ACE scale, which measures several dimensions of
Expected (E) and observed (O) number of CUD cases for external validation data.
social inequality, including childhood maltreatment, parental separa­
n E O E/O tion and divorce, and household criminality and incarnation.
Risk quintile groups There are few limitations in this study. Add Health data are relatively
Group 1 114 3.66 3 1.22 old and do not capture recent changes in the cannabis access landscape
Group 2 114 5.25 6 0.88
due to the introduction of new cannabis-based products and methods of
Group 3 114 6.80 3 2.27
Group 4 114 9.44 9 1.05 use (Knapp et al., 2019; Spindle et al., 2019). Moreover, Add Health did
Group 5 114 20.14 20 1.01 not measure neurocognitive and neuro-imaging data that may be
Biological sex important in predicting SUD. Unfortunately, to our knowledge, there is
Male 293 27.89 29 0.96 no other publicly available dataset wherein the participants are na­
Female 277 17.40 12 1.45
ACE scale
tionally representative, have been longitudinally followed from ado­
Below median 318 21.12 19 1.11 lescence/youth to adulthood, and have clinical measures of SUD and its
Above median 252 24.17 22 1.10 potential risk factors measured. Nonetheless, the known personal factors
Conscientiousness scale that make one susceptible to SUD are likely to remain important even
Below median 335 29.87 28 1.07
with the increasing prevalence of cannabis use (Afuseh et al., 2020; CDC,
Above median 235 15.43 13 1.19
Neuroticism scale 2020). As newer and more comprehensive data become available,
Below median 289 18.65 18 1.04 potentially including neurocognitive and neuro-imaging data as well, it
Above median 281 26.64 23 1.16 will be important to build new models using them and compare with the
Openness scale proposed model.
Below median 366 25.06 19 1.32
Also, some participants had missing data in one or more waves
Above median 204 20.23 22 0.92
Delinquency scale (Supplementary Table 1 shows percentage of missing values for each
Below median 286 14.32 13 1.10 predictor). Although this contributed to the overall amount of missing
Above median 284 30.97 28 1.11 data for cross-sectional predictors, a longitudinal predictor could be
Peer cannabis use
included for a participant provided there was at least one wave in which
Below median 285 15.67 19 0.82
Above median 285 29.62 22 1.35 the predictor was measured. We did not attempt to impute missing data
because variables related to substance use are not amenable to impu­
tation, e.g., the variable past 12 months alcohol days is undefined (and
literature. In particular, it is known that males are more likely to develop missing) for a non-user of alcohol and should not be imputed). More­
CUD than females (Hayatbakhsh et al., 2009; Jing et al., 2020; Meier over, there were no predictors that had a strong relationship with CUD
et al., 2016). In line with our finding that peer cannabis use increases the (based on univariate analyses) and also had a large proportion of missing
likelihood of CUD, a recent study reported that peer substance use in­ data except for past 12 months alcohol use. This variable had 7.85%
creases the likelihood of becoming a user of cannabis and other sub­ missing values and about half of them could not be imputed due to the
stances (Lowe et al., 2020). Three of our seven predictors are related to above- mentioned reason. Nonetheless, we tried adding this predictor to
personality traits, which have been previously identified as important in the final model and found that it did not increase the predictive accuracy
predicting substance use and dependence (Rajapaksha et al., 2020; of the model.
Zoboroski et al., 2021). A recent study identified several We included personality and ACE related variables from wave IV.
delinquency-related activities to be important in predicting SUD (Jing Even though the ACEs were measured in wave IV, they are retrospective
et al., 2020). Moreover, individuals with more delinquent behavior are measures that occurred before age 18 (much before wave IV). Moreover,
more likely to start using substances at a young age and to develop drug for someone with age of CUD onset less than 18, we counted only those
use disorders (Koh et al., 2017; Richmond-Rakerd et al., 2016). Previous ACEs that occurred before the CUD onset age. With personality traits,
studies have also identified childhood adverse events as an important such chronological ordering could not be ensured. However, there is
predictor for predicting substance use and dependence outcomes evidence from the literature that the personality traits included in this
(Hayatbakhsh et al., 2009; Moss et al., 2020). Some seemingly important study are relatively stable over time (Caspi et al., 2005; Damian et al.,
predictors such as personal substance use and socio-demographics got 2019).
excluded during our initial variable filtering or variable selection steps. These limitations are, however, outweighed by the various strengths
It is possible that their effects are partially captured by the variables in of the study, with the final product being a novel and methodologically
the final model. rigorous Bayesian learning model for CUD risk prediction in adulthood
The relationship between social inequality and substance use is based on risk factors from adolescence and young adulthood. Moreover,
currently of great scientific interest. Add Health has risk factors such as the model validated well on external data. Its discrimination and cali­
childhood welfare status, neighborhood status, etc., which are measures bration performance on external data compared favorably with those of
of social inequality, but these did not pass our initial variable filtering. the widely used risk prediction models for various diseases/disorders
Nonetheless, there is evidence that ACEs are highly associated with low (Chowdhury et al., 2018; Costantino et al., 1999; Min et al., 2014;

5
R.M.D.S. Rajapaksha et al.
Spiegelman et al., 1994). Although future validation studies are
important for building more confidence, the model is ready to be
considered for potential adoption in practice. To aid in this task, an R
package is under construction (relevant steps are provided in Supple­
mentary Materials). The model can help in identifying adolescent or
young adult cannabis users who are at high risk of developing CUD in
adulthood. Such users may then be provided with appropriate inter­
vention and prevention measures to help them divert from the path
towards CUD. The model may be also helpful in medical settings where
patients are considering using medical cannabis in consultation with
clinicians.
Role of funding sources
This work was funded by the University of Texas at Dallas SPIRe seed
grant. The sponsor had no role in the study design, collection, analysis or
interpretation of data, writing the manuscript and the decision to submit
this manuscript for publication.
CRediT authorship contribution statement
SB, PKC, and RMDR conceived the study. RMDR carried out all data
pre-processing and analyses. SB and PKC supervised RMDR throughout
the entire project. FF provided subject matter expertise in designing the
study and interpreting the results. All authors participated in inter­
preting the results and writing manuscript. All authors have read and
approved the final version of the manuscript.
Acknowledgement
The data used in this work are from Add Health, a program project
directed by Kathleen Mullan Harris and designed by J. Richard Udry,
Peter S. Bearman, and Kathleen Mullan Harris at the University of North
Carolina at Chapel Hill and funded by grant P01-HD31921 from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, with cooperative funding from 23 other federal agencies
and foundations. Information on how to obtain the Add Health data files
is available on the Add Health website (http://www.cpc.unc.edu/addh
ealth). No direct support was received from grant P01-HD31921 for
this analysis. The authors thank Thanthirige Lakshika Ruberu for help­
ing with initial exploration of the data.
Declaration of competing interest
None.
Appendix A. Supporting information
Supplementary data associated with this article can be found in the
online version at doi:10.1016/j.drugalcdep.2022.109476.
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