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Cannabis use and cannabis use disorders among individuals with

mental illness

Shaul Lev-Rana,b,c,d,, Bernard Le Foll c,e, f ,g, Kwame McKenzie a,b,g,h,Tony P. Georgeg, i , j, Jrgen Rehmb, k

aSocial Aetiology of Mental Illness (SAMI) CIHR Training Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

bSocial and Epidemiological Research Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

cAddictions Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

dAddiction Medicine Services, Department of Psychiatry, Sheba Medical Center, Tel Hashomer, Israel

eTranslational Addiction Research Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

fDepartments of Family and Community Medicine, Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada

gDepartment of Psychiatry, University of Toronto, Toronto, Ontario, Canada

hSocial Equity and Health Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

iSchizophrenia Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

jDivision of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto, Ontario, CanadakDalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

Abstract

Background: National epidemiological surveys have reported increased rates of cannabis use and cannabis use disorders (CUDs) among

individuals with mental illness. However, this subject has not been sufficiently investigated, particularly given limitations in diagnostic tools

used and lack of data pertaining to frequency of cannabis used.

Objectives: To examine the prevalence of cannabis use and CUDs among individuals with a wide range of mental illness.

Method: We analyzed data on 43,070 respondents age 18 and above from the National Epidemiologic Survey on Alcohol and Related

Conditions, a nationally representative survey conducted from 2001 to 2002. Main outcome measures included rates of cannabis use byfrequency (at least weekly and less than weekly use) and DSM-IV CUDs according to the number and type of axis I and axis II psychiatric

diagnoses, assessed by the Alcohol Use Disorders and Associated Disabilities Interview Schedule-IV. We estimated the proportion of cannabis

used by individuals with mental illness using reported daily dose and frequency of cannabis used by individuals with and without mentalillness.

Results: Rates of weekly cannabis use, less than weekly cannabis use and CUDs among individuals with 12-month mental illness were 4.4%,

5.4% and 4.0%, respectively, compared to 0.6%, 1.1% and 0.4%, respectively, among individuals without any 12-month mental illness

(Pb0.0001 for all comparisons). The odds ratio for cannabis use among individuals with 12-month mental illness vs. respondents without

any mental illness was 2.5, and the odds of having a CUD among individuals with 12-month mental illness were 3.2, after adjusting for

sociodemographic variables and additional substance use disorders. Cannabis use and CUDs were particularly associated with bipolar

disorder, substance use disorders and specific (anti-social, dependant and histrionic) personality disorders. Persons with a mental illness in the

past 12 months represented 72% of all cannabis users and we estimated they consumed 83% of all cannabis consumed by this nationally

representative sample.

Conclusions: The current study provides further evidence of the strong association between cannabis use and a broad range of primary

mental illness. This emphasizes the importance of proper screening for frequent cannabis use and CUDs among individuals with primary

mental illness and focusing prevention and treatment efforts on this population.

2013 Elsevier Inc. All rights reserved.

1. Introduction

Cannabis is the most widely used illicit substance

worldwide [13]. Globally, the number of people who

have used cannabis at least once is estimated to be between

Available online at www.sciencedirect.com

Comprehensive Psychiatry xx (2013) xxxxxxwww.elsevier.com/locate/comppsych

Corresponding author. Centre for Addiction and Mental Health,

Toronto, ON, Canada M5N2N5. Tel.: +1 416 535 8501; fax: +1 416 260

4156.

E-mail address: [email protected] (S. Lev-Ran).

0010-440X/$ see front matter 2013 Elsevier Inc. All rights reserved.

http://dx.doi.org/10.1016/j.comppsych.2012.12.021
http://www.sciencedirect.com/science/journal/0010440Xhttp://dx.doi.org/10.1016/j.comppsych.2012.12.021http://dx.doi.org/10.1016/j.comppsych.2012.12.021http://dx.doi.org/10.1016/j.comppsych.2012.12.021mailto:[email protected]://dx.doi.org/10.1016/j.comppsych.2012.12.021http://dx.doi.org/10.1016/j.comppsych.2012.12.021mailto:[email protected]://dx.doi.org/10.1016/j.comppsych.2012.12.021http://dx.doi.org/10.1016/j.comppsych.2012.12.021http://dx.doi.org/10.1016/j.comppsych.2012.12.021http://www.sciencedirect.com/science/journal/0010440X

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125 and 203 million [3], and lifetime prevalence of cannabis

use among young adults in the United States (US) has been

reported to be around 50% [4]. Among past-year cannabis

users, prevalence of cannabis use disorders (CUDs) has been

estimated to be more than 35% [5].

Previous large national epidemiological surveys have

reported increased rates of cannabis use and CUDs among

individuals with mental illness. Population-based data collect-

ed in the early 1980s by the Epidemiologic Catchment Area

(ECA) study showed that roughly 50% of individuals with

DSM-III psychiatric disorders meet criteria for lifetime

diagnosis of CUDs [6]. The National Comorbidity Survey

(NCS) conducted in the early 1990s reported that 90% of

individuals with cannabis dependence have lifetime DSM-III

psychiatric disorders and that cannabis dependence signifi-

cantly increased the odds for a mood (OR=2.2) or anxiety

(OR=2.6) disorder [7]. Additional longitudinal reports have

explored the association between cannabis use and specific

psychiatric disorders. Buckner and colleagues [8] reported that

the odds of cannabis dependence among individuals withsocial anxiety disorder were almost 5 times more than among

individuals without social anxiety disorder. Hayatbakhsh and

colleagues [9] reported that individuals with externalizing

behaviors during childhood and adolescence had a signifi-

cantly increased risk (OR=2.5) of having a CUD in young

adulthood. Wittchen and colleagues [10] reported that in

longitudinal analyses, non-cannabis substance use disorders

(SUDs) and mood and anxiety disorders were associated with

increased risk of cannabis use and CUDs.

Nevertheless, many of these reports have not used

assessment tools which clearly differentiate primary psychi-

atric disorders and substance-induced disorders. This isparticularly important when exploring the association

between mental illness and cannabis use, as it is the only

way to conclude whether specific psychiatric disorders (such

as mood and anxiety disorders) are associated with higher

rates of cannabis use even when cannabis-induced psychiat-

ric disorders are ruled out. In addition, though previous

research implies that the association between mental health

problems and cannabis use is particularly affected by the

frequency of cannabis use [3,11], most reports on rates of

cannabis use among individuals with mental illness have

clustered all cannabis users into one category, without

reporting separately on different frequencies of cannabis

use and CUDs. Finally, previous reports have not reporteddifferentially on rates of cannabis use and CUDs across a

wide range of axis I and axis II psychiatric disorders.

The aim of this study was to analyze rates of cannabis use

and CUDs among individuals with a wide range of concurrent

primary mental illness, ruling out substance-induced psychi-

atric disorders. Though there is currently no standard for

high and low frequencies of cannabis use, we focused

differentially on individuals using cannabis less than once per

week and those using cannabis at least weekly. This was

based on several studies using these categories of frequency

of cannabis use when examining the association between

cannabis use and mental illness [1114]. We hypothesized

that individuals with concurrent primary mental illness have

significantly higher rates of frequent cannabis use and CUDs

compared to individuals without mental illness and that these

rates further increase as the number of primary mental

disorders increases.

We used data from the National Epidemiologic Survey on

Alcohol and Related Conditions (NESARC) to examine the

relationship between types of mental illness and patterns of

cannabis use. The NESARC is the largest epidemiological

survey to-date on mental illness and substance use, and the

first and only national survey to include specific diagnoses of

primary and substance-induced psychiatric disorders.

2. Methods

2.1. Participants and procedure

We analyzed cross-sectional data from a population-based national representative sample, the National Epidemi-

ological Survey of Alcohol and Related Conditions

(NESARC) study (Wave 1, 20012002) [15] conducted by

the National Institute on Alcohol Abuse and Alcoholism

(NIAAA). The research protocol, including informed

consent procedures, received full ethical review and approval

from the U.S. Census Bureau and U.S. Office of Manage-

ment and Budget. The interview was developed to advance

measurement of substance use and mental disorders in large-

scale surveys. Face-to-face interviews were conducted with

43,093 adults (response rate, 81%), aged 18 years and older

from the civilian non-institutionalized population residing in

the US, including the District of Columbia, Hawaii andAlaska. The NESARC sample was weighted to adjust for

probabilities of selection of a sample housing unit or housing

unit equivalent, the non-response at the household and

person levels, the selection of one person per household and

the oversampling of AfricanAmericans, Hispanics and

young adults (ages 1824). The weighted data were post-

stratified and adjusted to match the target population based

on the 2000 decennial census in terms of region, age, sex,

race and ethnicity [16]. Details regarding sampling, purpose

and weighting have been previously published [17].

Characteristics of interviewers, training and field quality

control have been described elsewhere [5].

2.2. Assessments

The Alcohol Use Disorder and Associated Disabilities

Interview ScheduleDSM-IV Version (AUDADIS-IV) was

used to assess substance use and psychiatric disorders [18].

The AUDADIS-IV has been reported to have excellent

reliability and validity in the US [17] and internationally

[19]. It includes an extensive list of symptom questions that

separately operationalizes DSM-IV criteria for SUDs and

additional axis I and axis II diagnoses.

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2.3. Cannabis use and cannabis use disorders (CUDs)

Cannabis use in this study referred to cannabis use in the

last 12 months. Respondents were asked about frequency of

cannabis use. We categorized cannabis users according to

frequency of use, dividing them into at least weekly and

less than weekly cannabis users. Individuals who did not

provide this information (n = 23) were excluded fromanalyses pertaining to frequency of cannabis use. Doses of

cannabis used were measured as number of joints consumed

on days that cannabis was used in the last 12 months. CUDs

referred to cannabis abuse or dependence in the last

12 months as defined by DSM-IV.

2.4. Mental Illness

Any psychiatric disorder in this study referred to any axis

I, axis II or SUD in the last 12 months. Axis I disorders

included mood (major depressive disorder, bipolar I, bipolar

II and dysthymia) and anxiety (panic disorder, social anxiety

disorder, specific phobia, generalized anxiety disorder)

disorders. In the case of all mood and anxiety disorders,

we included only primary mental illness and excluded all

cases of substance-induced mental disorders as diagnosed in

the AUDADIS-IV. Primary (non substance-induced) mood

and anxiety disorders were defined if: (1) the respondent did

not use alcohol or drugs in the previous 12 months; (2) the

episode(s) did not occur in the context of drug or alcohol

intoxication or withdrawal; (3) the episode(s) started before

initiation of drug or alcohol or (4) the episode(s) began after

drug or alcohol consumption began, but persisted for

more than 1 month after cessation of intoxication or

withdrawal. Respondents were classified as having indepen-dent (primary) mood and anxiety disorders if none or only

some of their episodes were substance-induced [20]. SUDs

referred to any alcohol or drug (excluding cannabis) abuse or

dependence. The substances included in this study were

cocaine (including crack cocaine), heroin, hallucinogens,

inhalants/solvents, sedatives, tranquilizers, opioids and

amphetamines. Axis II disorders included any of the

following personality disorders: paranoid, schizoid, histri-

onic, antisocial, obsessivecompulsive, dependent, and

avoidant personality disorders.

2.5. Statistical analysis

Respondents with any 12-month mental illness were

examined with respect to demographic characteristics (sex,

age, educational level, household income, marital status,

urbanicity, race/ethnicity and region). Prevalence of weekly

cannabis use, less than weekly cannabis use and CUDs

among individuals with and without any primary psychiatric

diagnosis in the last 12-months were calculated with cross-

tabulations providing 95% confidence intervals. We used the

2-statistic to compare differences between groups in the

proportion of cannabis users and individuals with CUDs. As

it has been repeatedly shown that patterns of cannabis use, as

well as prevalence of CUDs vary greatly between men and

women [5,21], these analyses were also conducted separately

by gender. We used logistic regression to analyze the

odds for any 12-month mental illness among different

demographic groups, and to analyze the odds for cannabis

use and CUDs among individuals with 12-month mental

illnesses, while controlling for sociodemographic variables

(age, sex, household income, region, educational level,

marital status and urbanicity) and any non-cannabis SUDs.

In order to examine the effect of age on the relationship

between cannabis use and mental illness, we calculated the

odds for 12-month cannabis use among individuals with and

without mental illness by age group and controlling for other

sociodemographic variables. We used the t-test to compare

daily dose of cannabis used (measured as number of joints

used on days cannabis is consumed) among individuals with

and without 12-month mental illness. We used the Mantel

Haenszel 2 test for trend to compare rates of cannabis use

according to the number of 12-month mental diagnoses. In

order to correct for multiple testing, we used an adjustedp-value according to the maximum number of categories

included in an analysis (ie, 8 categories of axis I diagnoses).

Based on the Bonferroni correction, we calculated that in

order to maintain 95% level of confidence we use an adjusted

p value of pb0.00625. Based on the formula presented by

Lasser et al. [22], we estimated the proportion of all cannabis

used in the US that was consumed by persons with mental

illness using the following calculation:

MD1F1=ND2F2 MD1F1

where M = the percentage of current cannabis users with

mental illness; D1 =the mean dose of joints per day

consumed by current cannabis users with mental illness;

F1=the mean number of days in the last year in which

cannabis was consumed by current cannabis users with

mental illness; N=the percentage of current cannabis users

without mental illness; D2 =the mean dose of joints per day

consumed by current cannabis users without mental illness

and F2=the mean number of days in the last year in which

cannabis was consumed by current cannabis users without

mental illness. Though this formulation was developed for

cigarette smoking, in which standardization is more readily

possible, it has merit when dealing with cannabis as well.One of the major challenges in cannabis research is assessing

intensity of cannabis used and both dose and frequency have

been proposed as proxy terms for the intensity of use [23].

Moreover, substance use clinical trials frequently use daily

dose of substances as the primary outcome measure [24].

Accordingly, despite potential errors in estimation, this

formulation is useful as it combines daily dose and

frequency. We used the same formulation to calculate the

portion of cannabis used among occasional and regular

cannabis users with mental illness and among individuals

with SUDs.

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All results were based on population weighted data to

allow conclusions representative for the US. To accurately

estimate variances taking the NESARC sample design

components into account, analyses were conducted with

Software for Survey Data Analysis (SUDAAN) Version 10

[25], a software program that uses Taylor series lineari-

zation to make adjustments for the NESARC's sample

design characteristics.

3. Results

3.1. Sociodemographic characteristics and association

between 12-month mental illness and concurrent cannabis

use and CUDs

The prevalence of cannabis use and of CUDs among

individuals with 12-month mental illness according to

demographics is presented in Table 1. The population

prevalence of 12-month cannabis use was 4.1%. In the

general population, 2.4% reported less than weekly cannabis

use, 1.7% reported at least weekly cannabis use and 1.5%

had a CUD. The majority of cannabis users (56.4%) were in

the young (1829) age group: among individuals with 12-

month mental illness, 59.2% of cannabis users were in the

young age group vs 49.2% of cannabis users among

individuals without 12-month mental illness. The prevalence

of cannabis use and CUDs among individuals with 12-month

mental illness was 9.9% and 4.0%, respectively, compared to

1.6% and 0.4% among individuals without any mental

illness in the last 12 months. Individuals with 12-month

mental illness represented 72.2% of all individuals who used

cannabis in the last 12 months and 81.8% of individuals with

12-month CUDs. Prevalence of mental illness was signifi-

cantly higher among individuals using cannabis at least

weekly (77.2%) compared to individuals using cannabis less

than weekly (68.7%; pb0.01). Respondents with any axis I,

axis II or SUD had elevated rates of both weekly cannabis

use, less than weekly cannabis use and CUDs in the last

12 months (Table 2). Rates of cannabis use and CUDs were

particularly elevated among individuals with Bipolar I

Table 1

Prevalence and logistic regression analyses of 12-month mental illness by selected sociodemographic characteristics.

Variable 12-month mental illness (N = 12,659)

prevalence, % (95% CI)

OR

Sex

Men (ref) 30.0 (28.831.3) 1.0

Women 29.6 (28.330.9) 0.98 (0.931.04)

Age

1829 (ref) 38.4 (36.540.4) 1.0

3044 32.2 (30.633.8) 0.76 (0.710.81)

4564 28.1 (26.829.4) 0.63 (0.580.67)

65+ 16.8 (15.7

17.8) 0.32 (0.29

0.35)Education

less than high school (ref) 22.6 (20.524.9) 1.0

high school 30.4 (29.131.8) 1.50 (1.321.70)

some college or higher 30.1 (28.931.4) 1.48 (1.301.68)

Household income

$0$19,999 (ref) 31.4 (29.932.9) 1.0

$20,000$39,999 31.0 (29.332.7) 0.98 (0.901.07)

$40,000$59,000 29.7 (28.331.1) 0.92 (0.860.99)

$60,000 or above 28.0 (26.729.4) 0.85 (0.780.92)

Marital status

Married (ref) 26.4 (25.227.6) 1.0

separated/divorced/widowed 32.21 (30.633.7) 1.32 (1.341.41)

never married 37.7 (36.039.4) 1.69 (1.591.79)

Urbanicity

Urban (ref) 30.8 (28.633.1) 1.0Rural 29.3 (28.330.4) 0.93 (0.841.04)

Race/ethnicity

White (ref) 30.5 (29.431.6) 1.0

Black 29.5 (27.931.2) 0.95 (0.891.03)

American Indian 41.6 (37.146.3) 1.63 (1.351.95)

Asian 19.9 (16.923.2) 0.56 (0.470.68)

Hispanic 27.1 (25.328.9) 0.85 (0.770.93)

Region

Northeast (ref) 27.9 (25.630.3) 1.0

Midwest 32.6 (29.835.6) 1.25 (1.051.49)

South 27.8 (26.529.2) 1.0 (0.871.14)

West 31.6 (28.734.6) 1.19 (1.001.43)

Abbreviations: OR = Odds ratio, ref= reference.


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disorder (Table 3) and specific (anti-social, and histrionic)

personality disorders (Table 4).

The relationship between cannabis use and mental illness

persisted when we controlled for sociodemographic vari-

ables. Compared with respondents without 12-month mental

illness, those with any 12-month mental illness were

significantly more likely to use cannabis in the last

12 months (OR=5.2, 95% CI=4.55.9). When additionally

controlling for any non-cannabis SUD, the increased odds

for cannabis use among individuals with mental illness were

retained (OR=2.5, 95% CI=2.13.0). Adjusting for socio-

demographic variables, the odds of having a CUD were 8.0

(95% CI= 6.210.3) among individuals with 12-month

mental illness compared to those without 12-month mental

illness. After additional adjustment for non-cannabis SUDs,

the odds ratio for having a CUD among individuals with

mental illness compared to those without mental illness was

3.2 (95% CI=2.24.6).

We calculated the odds for 12-month cannabis use among

individuals with and without mental illness by age group andcontrolling for other sociodemographic variables. In the 18

29 year age group, individuals with any 12-month mental

illness were significantly more likely to use cannabis in the

last 12 months (OR=5.8, 95% CI=4.87.1) compared to

those without mental illness. The association was further

retained in other age groups: in the 3044 and the 45

64 year age group, individuals with any 12-month mental

illness were significantly more likely to use cannabis in the

last 12 months (OR = 8.2 (95% CI= 5.612.0) and 7.4 (95%

CI=4.611.9), respectively) compared to those without any

mental illness. In the 65+ age group, this association was not

retained (OR=5.0, 95% CI=0.548.3), though it should be

noted that the prevalence of cannabis use in this age group

was generally low (0.04%).

3.2. Daily dose of cannabis used

The mean number of joints consumed (on days that

cannabis was used) by individuals with 12-month mentalillness was 2.2, compared to 1.6 among individuals without

any mental illness in the last 12 months (pb0.0001). Among

individuals with 12-month prevalence of mental illness, the

mean number of joints among individuals using cannabis

less than weekly was 1.4 joints per day, compared to 3.1

joints per day among individuals using cannabis at least

weekly (pb0.0001).

3.3. Cannabis use and multiple psychiatric diagnoses

Persons with multiple 12-month psychiatric diagnoses

had higher rates of weekly and less than weekly cannabis use

than persons with only 1 DSM-IV diagnosis (p b0.0001,Fig. 1).

3.4. Proportion of cannabis used by individuals with

mental illness

We estimated that persons with a 12-month mental illness

consumed 83% of all cannabis consumed in the US. Among

individuals with mental illness, 2.4% of the cannabis was

used by individuals using cannabis less than weekly, and

97.6% was used by individuals using cannabis at least

weekly. Sixty percent of all cannabis was consumed by

individuals with SUDs. Of these, 46% used cannabis at least

Table 2

Prevalence of cannabis use and cannabis use disorders according to 12-month mental illness status (n=43,093).

Less than weekly, % (95% CI) At least weekly, % (95% CI) CUD, % (95% CI)

Total 2.4 (2.22.6) 1.7 (1.51.9) 1.5 (1.31.6)

No mental illness 1.1 (0.91.2) 0.6 (0.50.7) 0.4 (0.30.5)

Men 1.4 (1.11.6) 0.8 (0.61.0) 0.6 (0.40.7)

Women 0.8 (0.61.0) 0.3 (0.20.5) 0.2 (0.10.3)

Any mental illness 5.4 (4.96.0)

4.4 (3.95.0)

4.0 (3.64.5)

Men 7.2 (6.38.2) 6.6 (5.77.5) 6.0 (5.36.9)

Women 3.8 (3.34.4) 2.4 (2.03.0) 2.1 (1.72.5)

Any axis I disordera 4.4 (3.85.1) 3.8 (3.24.5) 3.5 (3.04.2)

Men 6.5 (5.27.9) 7.1 (5.78.8) 6.4 (5.08.1)

Women 3.3 (2.73.9) 2.0 (1.62.6) 2.0 (1.62.5)

Any SUDb 12.3 (11.013.7) 10.4 (9.211.8) 10.2 (9.111.4)

Men 12.7 (11.014.5) 11.6 (10.013.5) 11.3 (9.813.0)

Women 11.5 (9.413.8) 7.7 (6.09.8) 7.1 (6.19.8)

Any axis II disorderc 5.0 (4.35.8) 5.3 (4.56.2) 4.8 (4.15.5)

Men 6.2 (5.07.5) 7.4 (6.29.0) 6.8 (5.78.2)

Women 3.8 (3.14.7) 3.1 (2.54.0) 2.6 (2.13.4)

Abbreviations: CUD=cannabis use disorders.a Any mood (Bipolar I, Bipolar II, Major Depressive Disorder, dysthymia) or anxiety (panic, social phobia, specific phobia, Generalized Anxiety Disorder)

disorder.b Any alcohol or drug use disorder (excluding cannabis).c Any antisocial, avoidant, dependent, paranoid, schizoid, histrionic personality disorder. Significantly different from respondents without any psychiatric disorder, p0.0001.


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weekly; we estimated they consumed 97.5% of all cannabis

consumed by individuals with SUDs.

4. Discussion

We found that persons with mental illness are almost 10

times as likely to use cannabis weekly or suffer from a CUD,

and more than 5 times as likely to use cannabis less than

weekly, compared to individuals without mental illness.

Though increased rates of cannabis use among individuals

with mental illness are well-known, our findings add toprevious findings in the following: (1) we included only

individuals with primary (e.g., not substance-induced) mood

and anxiety disorders based on DSM-IV diagnostic criteria;

(2) we differentiated cannabis users by frequency (3) we

report on a wide range of primary axis I and axis II disorders

and (4) we estimated percentage of cannabis consumed by

individuals with mental illness based on frequency of use

and reported daily doses, as an additional measure of the

association between mental illness and cannabis use. The

unique data collected in the NESARC pertaining to cannabis

use and mental illness allowed for these analyses.

Among non-SUD axis I mental disorders, CUDs and at-

least weekly cannabis use were particularly prevalent among

individuals with bipolar I disorder, with approximately 10%

of individuals fulfilling criteria of a CUD or reporting using

cannabis at least once per week. This is lower than rates of

cannabis related problems cited in various studies among

individuals with bipolar disorder, which are as high as 50%

[26]. These differences in prevalence rates may be accounted

for by both criteria and information variance [27]. Differ-

ences in instruments used (for example AUDADIS-IV in the

NESARC vs. the National Institute of Mental Health

Diagnostic Interview Schedule (DIS) and CompositeInternational Diagnostic Interview (CIDI) in the ECA and

NCS, respectively) have been reported to affect prevalence

rates in population-based studies [28]. It has been further

suggested that respondents may be less forthcoming in

surveys conducted by government agencies to reveal

information pertaining to substance use. Nevertheless, this

would not seem to specifically affect individuals with

bipolar disorder; hence, the increased rate of frequent

cannabis use and CUDs among individuals with bipolar

disorder relative to individuals with other psychiatric

disorders should be noted.

Table 3

Prevalence of cannabis use and cannabis use disorders according to specific 12-month DSM-IV Axis I diagnoses (n = 43,093).


Any mood disorder 5.8 (4.86.9) 4.9 (4.15.9) 4.9 (4.15.9)

Men 7.9 (6.010.2) 8.9 (7.011.3) 6.3 (6.510.6)

Women 4.6 (3.75.7) 2.7 (2.13.6) 3.0 (2.33.9)

Bipolar I Disorder 8.4 (6.311.0) 9.6 (7.212.7) 9.4 (7.012.5)

Men 9.8 (6.614.1)

15.5 (10.722.1)

14.6 (10.220.3)

Women 7.3 (5.010.5) 5.2 (3.38.0) 5.5 (3.58.6)

Bipolar 2 Disorder 7.6 (4.812.0) 4.8 (2.88.3) 6.1 (3.610.0)

Men 5.6 (2.512.1) 7.6 (3.615.1) 8.8 (4.316.8)

Women 9.0 (5.015.7) 3.0 (1.36.7) 4.3 (2.18.4)

Major depression 4.8 (3.76.2) 3.4 (2.44.2) 3.1 (2.34.0)

Men 7.8 (5.411.3) 6.2 (4.29.0) 5.2 (3.67.5)

Women 3.3 (2.44.5) 1.8 (1.22.8) 2.0 (1.33.1)

Dysthymia 3.8 (2.55.8) 6.0 (4.38.4) 5.7 (3.98.4)

Men 4.9 (2..69.0) 10.8 (6.916.3) 8.7 (5.014.6)

Women 3.3 (1.95.9) 3.8 (2.36.1) 4.4 (2.77.1)

Any anxiety disorder 4.0 (3.44.8) 3.6 (2.94.5) 3.2 (2.53.9)

Men 6.2 (4.88.0) 7.0 (5.29.3) 5.7 (4.27.7)

Women 2.9 (2.33.7) 2.0 (1.52.7) 2.0 (1.52.6)

Panic disorder 4.4 (3.16.3) 5.9 (4.18.4) 5.0 (3.67.1)

Men 7.3 (4.411.8) 11.9 (7.318.8) 8.8 (5.414.2)

Women 3.3 (1.95.4) 3.5 (2.25.4) 3.5 (2.25.6)

Social phobia 5.7 (4.27.7) 3.4 (2.44.9) 3.9 (2.85.4)

Men 9.5 (6.314.0) 4.8 (2.97.8) 5.0 (3.08.4)

Women 3.5 (2.35.3) 2.6 (1.54.5) 3.2 (2.05.1)

Specific phobia 3.4 (2.74.4) 3.8 (2.94.9) 2.9 (2.23.9)

Men 5.0 (3.57.2) 7.9 (5.511.0) 5.6 (3.68.5)

Women 2.7 (2.03.7) 2.0 (1.32.9) 1.8 (1.22.6)

GAD 4.5 (3.16.4) 5.8 (4.08.3) 5.5 (3.78.3)

Men 5.9 (3.310.5) 12.3 (7.119.5) 10.1 (5.517.9)

Women 3.9 (2.46.2) 3.2 (2.05.1) 3.6 (2.35.8)

Abbreviations: CUD=cannabis use disorders. Significantly different from respondents without any psychiatric disorder, p 0.0001. Significantly different from respondents without any psychiatric disorder, p b0.001.


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Individuals with alcohol and drug use disorders were at a

particularly high risk for weekly cannabis use; more than

10% of these individuals used cannabis at least once per

week, and rates of CUDs in this population were more than

10%. Multiple substance use may be influenced by common

neurobiological factors, given that different substances act

upon similar brain loci and involve similar neurotransmitter

systems [29,30]. In addition, social factors and drug

availability should be considered. Patterns of drug initiation

have been found to vary across countries and cultures [3],

suggesting that social settings that facilitate specific drug use

may be particularly important. Though cannabis use and

CUDs have been largely overlooked in treatment settings for

substance use problems, the rates of admission to nationally

funded treatment centers with cannabis stated as the primary

problem-drug are gradually increasing. The rate of treatment

admission with cannabis as the primary substance almost

doubled between 1993 and 1999 [31]. In 2008, 16.6% of

individuals discharged from treatment facilities reportedcannabis as their primary substance of abuse [32]. Our

findings emphasize the importance of assessing for frequent

cannabis use and CUDs among individuals with any alcohol

or drug use disorder.

Among individuals with personality disorders, CUDs and

at-least weekly cannabis use disorders were particularly

prevalent among individuals with antisocial and histrionic

personality disorders. Among these, antisocial personality

disorder has been particularly shown to be associated with an

increased risk for persistence of CUDs during a 3-year

follow-up [33]. Though the increased association between

substance use disorders and cluster B personality disorders is

well known [34], additional investigation of CUDs among

individuals with personality disorders belonging to other

clusters, which takes into account temporal relationships

(such as that conducted by Hasin and colleagues [33]), can

help in elucidating mechanisms of these co-morbidities.

Almost without exception, the rates of cannabis use and

CUDs were higher among men compared to women. This

echoes findings on rates of cannabis use and CUDs in the

general population in previous population-based surveys (for

example, the National Longitudinal Alcohol Epidemiologic

Survey (NLAES, 19911992)) as well as in the NESARC

sample [5]. Though it is possible that these gender differences

reflect differences in effects of cannabis, as well as

susceptibility to frequent cannabis use and CUDs [35], it

has also been suggested that these gender differences can be

explained by differences in opportunities to use cannabis and

other drugs, and that given the initial opportunity to use

drugs, men and women are equally likely to move on tofrequent cannabis use [36,37]. Among individuals with

mental illness, both increased opportunities for use amongst

men as well as potential increased susceptibility for frequent

use and misuse should be taken into account even in those

disorders which are more prevalent among women, such as

depression and anxiety disorders.

The association between mental illness and cannabis use

was pervasive across most age groups. This implies that

though cannabis use is generally more prevalent among

younger people, the prevalence of cannabis use is higher

among individuals with mental illness in older adults as well.

Table 4

Prevalence of cannabis use and cannabis use disorders according to specific 12-month DSM-IV Axis II diagnoses (n=43,093).


Antisocial PD 10.1 (8.112.5) 13.4 (11.215.9) 12.0 (10.014.5)

Men 9.8 (7.313.0) 13.6 (11.016.7) 13.1 (10.516.4)

Women 10.8 (7.615.2) 12.7 (9.417.0) 9.1 (6.412.9)

Avoidant PD 5.7 (4.18.0) 5.3 (3.67.7) 5.6 (3.93.7)

Men 9.7 (6.214.7)

9.6 (5.915.3) 10.1 (6.515.3)

Women 3.2 (1.95.4) 2.5 (1.44.5) 2.7 (1.64.7)

Dependent PD 7.1 (3.513.9) 10.5 (5.419.5) 14.2 (8.522.8)

Men 11.4 (3.928.9) 24.3 (12.242.7) 30.0 (16.947.4)

Women 4.7 (2.010.8) 2.9 (1.17.1) 5.5 (2.710.6)

ObsessiveCompulsive PD 3.7 (2.94.7) 3.3 (2.54.4) 3.5 (2.74.5)

Men 4.8 (3.46.6) 5.3 (3.77.4) 4.9 (3.96.8)

Women 2.6 (1.92.7) 1.5 (1.02.4) 2.2 (1.53.2)

Paranoid PD 5.7 (4.57.2) 7.0 (5.49.0) 5.8 (4.57.5)

Men 6.9 (4.610.3) 11.6 (8.515.7) 9.0 (6.512.4)

Women 4.9 (3.66.7) 3.7 (2.65.1) 3.6 (2.65.0)

Schizoid PD 3.9 (2.85.5) 6.3 (4.78.4) 5.2 (3.87.0)

Men 5.0 (3.27.8) 8.2 (5.512.0) 6.2 (3.99.7)

Women 2.9 (1.75.0) 4.5 (3.16.6) 4.2 (2.86.1)

Histrionic PD 9.0 (7.111.5) 9.9 (7.113.6) 9.8 (7.313.1)

Men 10.2 (7.214.3)

14.8 (10.121.0)

13.9 (9.919.4)

Women 7.9 (5.411.5) 5.1 (3.18.3) 5.8 (3.69.2)

Abbreviations: CUD=cannabis use disorders; PD=personality disorder. Significantly different from respondents without any psychiatric disorder, p0.0001. Significantly different from respondents without any psychiatric disorder, p b0.001.


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We found that the prevalence of cannabis use, both

weekly and less than weekly, increases with the increase in

number of DSM-IV psychiatric diagnoses. This is particu-

larly important given reports that the vast majority of mental

disorders are co-morbid disorders; results from the NCS

show that 79% of individuals with a lifetime mental disorder

had an additional co-morbid disorder. Frequent cannabis use

among individuals with mental illness is associated with

symptom exacerbation [38,39] and poorer treatment out-

comes [39,40]. Individuals with co-morbid mental illness

and substance use are at increased risk of higher rates of

hospitalization [41], homelessness or housing instability

[42], and increased treatment costs [43]. Nevertheless, there

is still a paucity of clinical data on the impact of cannabis use

on the prognosis of specific psychiatric disorders.

Why do individuals with mental illness consume more

cannabis? It has been suggested that such persons use

cannabis as a means of self-medication of psychiatric

symptoms [44]. Neurobiological research has implicated

that the endocannabinoid (eCB) system is highly expressed

in different brain regions and has regulatory functions and

that it may be deeply involved in many mental disorders

[45]. It is possible that cannabis use and mental illness sharecommon factors; the same factors that predispose people to

mental illness also increase their risk of cannabis use. These

common factors may include biological, personality, social

or environmental factors, or some combination of these

factors [23]. Finally, it is possible that cannabis use increases

the risk for developing mental illness. Evidence for an

association between cannabis use and the development of

psychotic disorders has accumulated [12]. There is a growing

consensus that those who use cannabis, particularly heavy

users and individuals who initiated cannabis use at a young

age, are at increased risk for developing psychotic disorders.

There is evidence pointing to an association between heavy

cannabis use and the development of depression [12].

Nevertheless, there is a scarcity of longitudinal studies

examining the association between cannabis use and the

development of various mental illnesses. Further longitudi-

nal studies with multiple waves which account for temporal

relationships between cannabis use and mental illness (such

as that conducted by Wittchen and colleagues [10]) are

important in elucidating the potential mechanisms involved

in this co-morbidity.

As is common in large-scale epidemiological surveys,

limitations of this study should be recognized. First,

information was based on self-reporting, allowing for recall

and social desirability biases. Second, because the NESARC

sample included only civilian households and quarters

populations, information on individuals in prisons is

missing. Since the prevalence of mental illness and substance

use has been reported to be high in prison populations [46],

this may affect calculations. Third, data do not include

adolescents, a particularly vulnerable population for canna-bis use [47]. Fourth, though the NESARC evaluated a large

number of common mental disorders, additional disorders in

which prevalence of cannabis use is known to be high have

not been included in the NESARC survey or were not

assessed using specific diagnostic criteria. Of particular

interest may be rates of cannabis use and CUDs among

individuals with psychotic disorders, which have been

reported to be particularly high [45]. Psychotic disorders in

the NESARC were assessed using a single question (Did a

doctor or other health professional diagnose schizophrenia or

psychotic illness or episode in the last 12 months). As this

method of assessment is substantially different from thediagnostic assessment of all other DSM-IV disorders

included in the NESARC, and may include an underestima-

tion of psychotic disorders, we chose not to include these

data in our study. It should be noted that the prevalence of

cannabis use in this sample of individuals with anxiety

disorders is lower than that reported in other samples [48].

There are several factors which may explain this. Differences

in instruments used (to assess both anxiety disorders and

substance use) have been reported to affect prevalence rates

in population-based studies [27,28]. Difference in survey

methodologies (e.g., coverage weight, data weighing) as

well as question text may also affect estimations. It has been

further suggested that respondents may be less forthcomingin surveys conducted by government agencies to reveal

information pertaining to substance use [49]. Any or all of

these considerations may have affected the rate of cannabis

use in our sample. Finally, given the expected variability in

potency of cannabis used and taking into account the

variance of in estimating standard doses of cannabis (e.g.,

joints) [24], the limitation of applying the self-reported dose

of cannabis used to the Lasser formulation should be

acknowledged and the estimation of percentage of cannabis

consumed by individuals with mental illness referred to with

caution. Nevertheless, it seems that these challenges in

0

5

10

15

20

25

0 1 2 3 4 >4

No. of 12-month Psychiatic Diagnoses

Less than weekly cannabis use

At least weekly cannabis use

Fig. 1. Patterns of cannabis use according to the number of 12-month DSM-

IV psychiatric diagnoses.


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estimating doses of cannabis used will not resolve soon and

even if not perfectly precise, this application of the Lasser

formulation helps in elucidating the large impact of mental

illness of cannabis use.

Extrapolating our results to the general population, we

estimate that persons with a diagnosable primary mental

illness constitute almost 75% of all cannabis users, with a

particularly high prevalence of more frequent cannabis use

and CUDs in this population. Our findings emphasize the

importance of proper screening for frequent cannabis use and

CUDs particularly among individuals with mental illness,

and focusing prevention and treatment efforts on the mentally

ill. The largely disparate services for mental health and

substance abuse pose serious challenges of service provision

for this population. Treatment fragmentation between mental

health and substance abuse services may mean that in-

dividuals with co-morbid cannabis use disorders and mental

health problems do not receive adequate care. This results in

suboptimal treatment outcomes in a population that already

suffers some of the poorest outcomes in terms of illness.

References

[1] European Monitoring Centre for Drugs and Drug Addiction. Annual

report. Luxembourg: Publications Office of the European Union; 2010.

[2] United Nations Office on Drugs and Crime. World drug report. Vienna

2010.

[3] Degenhardt L, Hall W. Extent of illicit drug use and dependence, and

their contribution to the global burden of disease. Lancet 2012;

379(9810):55-70.

[4] Substance Abuse and Mental Health Services Administration. National

survey on drug use and health. Rockville MD: Substance Abuse and

Mental Health Services Administration; 2008.

[5] Compton WM, Grant BF, Colliver JD, Glantz MD, Stinson FS.

Prevalence of marijuana use disorders in the United States: 19911992

and 20012002. JAMA 2004;291(17):2114-21.

[6] Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, et al.

Comorbidity of mental disorders with alcohol and other drug abuse.

Results from the Epidemiologic Catchment Area (ECA) Study. JAMA

1990;264(19):2511-8.

[7] Kessler RC, Nelson CB, McGonagle KA, Edlund MJ, Frank RG, Leaf

PJ. The epidemiology of co-occurring addictive and mental disorders:

implications for prevention and service utilization. Am J Orthopsy-

chiatry 1996;66(1):17-31.

[8] Buckner JD, Schmidt NB, Lang AR, Small JW, Schlauch RC,

Lewinsohn PM. Specificity of social anxiety disorder as a risk factor

for alcohol and cannabis dependence. J Psychiatr Res 2008;42(3):

230-9.

[9] Hayatbakhsh MR, McGee TR, Bor W, Najman JM, Jamrozik K,

Mamun AA. Child and adolescent externalizing behavior and cannabis

use disorders in early adulthood: an Australian prospective birth cohort

study. Addict Behav 2008;33(3):422-38.

[10] Wittchen HU, Frohlich C, Behrendt S, Gunther A, Rehm J,

Zimmermann P, et al. Cannabis use and cannabis use disorders and

their relationship to mental disorders: a 10-year prospective-longitu-

dinal community study in adolescents. Drug Alcohol Depend

2007;88(Suppl 1):S60-70.

[11] Hall W, Degenhardt L. Adverse health effects of non-medical cannabis

use. Lancet 2009;374(9698):1383-91.

[12] Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB,

Burke M, et al. Cannabis use and risk of psychotic or affective mental

health outcomes: a systematic review. Lancet 2007;370(9584):319-28.

[13] Swift W, Coffey C, Degenhardt L, Carlin JB, Romaniuk H, Patton GC.

Cannabis and progression to other substance use in young adults:

findings from a 13-year prospective population-based study.

J Epidemiol Community Health 2011.

[14] Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, Hall W.

Cannabis use and mental health in young people: cohort study. BMJ

2002;325(7374):1195-8.

[15] Grant BF, Moore TC, Kaplan K. Source and accuracy statement: wave

1 National Epidemiologic Survey on Alcohol and Related Conditions(NESARC). Bethesda, Md: National Institute on Alcohol Abuse and

Alcoholism; 2003.

[16] Huang B, Grant BF, Dawson DA, StinsonFS, Chou SP, Saha TD, et al.

Raceethnicity and the prevalence and co-occurrence of Diagnostic

and Statistical Manual of Mental Disorders, Fourth Edition, alcohol

and drug use disorders and Axis I and II disorders: United States, 2001

to 2002. Compr Psychiatry 2006;47(4):252-7.

[17] Grant BF, Dawson DA, Stinson FS, Chou PS, Kay W, Pickering R.

The Alcohol Use Disorder and Associated Disabilities Interview

Schedule-IV (AUDADIS-IV): reliability of alcohol consumption,

tobacco use, family history of depression and psychiatric diagnostic

modules in a general population sample. Drug Alcohol Depend

2003;71(1):7-16.

[18] Grant BF, Hasin D. The Alcohol Use Disorder and Associated

Disabilites ScheduleDSM-IV Version. Bethesda, MD: NationalInstitute on Alcohol Abuse and Alcoholism; 2001.

[19] Chatterji S, Saunders JB, Vrasti R, Grant BF, Hasin D, Mager D.

Reliability of the alcohol and drug modules of the Alcohol Use

Disorder and Associated Disabilities Interview ScheduleAlcohol/

Drug-Revised (AUDADIS-ADR): an international comparison. Drug

Alcohol Depend 1997;47(3):171-85.

[20] Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton

W, et al. Prevalence and co-occurrence of substance use disorders and

independent mood and anxiety disorders: results from the National

Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen

Psychiatry 2004;61(8):807-16.

[21] Lev-Ran S, Imtiaz S, Taylor BJ, Shield KD, Rehm J, Le Foll B. Gender

differences in health-related quality of life among cannabis users:

results from the national epidemiologic survey on alcohol and related

conditions. Drug Alcohol Depend 2011.[22] Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D,

Bor DH. Smoking and mental illness: a population-based prevalence

study. JAMA 2000;284(20):2606-10.

[23] Degenhardt L, Hall W, Lynskey M. Exploring the association between

cannabis use and depression. Addiction 2003;98(11):1493-504.

[24] Mariani JJ, Brooks D, Haney M, Levin FR. Quantification and

comparison of marijuana smoking practices: blunts, joints, and pipes.

Drug Alcohol Depend 2011;113(23):249-51.

[25] Research Triangle Institute. Software for survey data analysis

(SUDAAN). 10 ed. Research Triangle Park, NC: Research Triangle

Institute; 2004.

[26] Cerullo MA, Strakowski SM. The prevalence and significance of

substance use disorders in bipolar type I and II disorder. Subst Abuse

Treat Prev Policy 2007;2:29.

[27] Klerman GL. Diagnosis of psychiatric disorders in epidemiologic fieldstudies. Arch Gen Psychiatry 1985;42(7):723-4.

[28] Regier DA, Kaelber CT, Rae DS, Farmer ME, Knauper B, Kessler RC,

et al. Limitations of diagnostic criteria and assessment instruments for

mental disorders. Implications for research and policy. Arch Gen

Psychiatry 1998;55(2):109-15.

[29] Koob GF, Le Moal M. Drug addiction, dysregulation of reward,

and allostasis. Neuropsychopharmacology : official publication of

the American College of Neuropsychopharmacology 2001;24(2):

97-129.

[30] Nutt DJ. The neurochemistry of addiction. Hum Psychopharmacol

1997;12:s53-8.

[31] Substance Abuse and Mental Health Services Administration. National

household survey on drug abuse: main findings, 1998. Rockville, MD:


7/28/2019 1-s2.0-S0010440X13000187-main.pdf

10/10

Substance Abuse and Mental Health Services Administration. Office

of Applied Studies; 2002.

[32] Substance Abuse and Mental Health Services Administration.

Treatment Episode Data Set (TEDS): 2008. Discharges from

Substance Abuse Treatment Services, DASIS Series: S-56, HHS

Publication No. (SMA) 114628. Rockville, MD: Substance Abuse

and Mental Health Services Administration; 2010. p. 55-6.

[33] Hasin D, Fenton MC, Skodol A, Krueger R, Keyes K, Geier T, et al.

Personality disorders and the 3-year course of alcohol, drug, andnicotine use disorders. Arch Gen Psychiatry 2011;68(11):1158-67.

[34] Taylor J. Substance use disorders and Cluster B personality disorders:

physiological, cognitive, and environmental correlates in a college

sample. Am J Drug Alcohol Abuse 2005;31(3):515-35.

[35] Greenfield SF, O'Leary G. Sex differences in marijuana use in the

United States. Harv Rev Psychiatry 1999;6(6):297-303.

[36] Van Etten ML, Neumark YD, Anthony JC. Malefemale differences in

the earliest stages of drug involvement. Addiction 1999;94(9):1413-9.

[37] Van Etten ML, Anthony JC. Comparative epidemiology of initial drug

opportunities and transitions to first use: marijuana, cocaine,

hallucinogens and heroin. Drug Alcohol Depend 1999;54(2):117-25.

[38] Arendt M, Rosenberg R, Fjordback L, Brandholdt J, Foldager L, Sher

L, et al. Testing the self-medication hypothesis of depression and

aggression in cannabis-dependent subjects. Psychol Med 2007;37(7):

935-45.[39] Goldberg JF, Garno JL, Leon AC, Kocsis JH, Portera L. A history of

substance abuse complicates remission from acute mania in bipolar

disorder. J Clin Psychiatry 1999;60(11):733-40.

[40] Bricker JB, Russo J, Stein MB, Sherbourne C, Craske M, Schraufnagel

TJ, et al. Does occasional cannabis use impact anxiety and depression

treatment outcomes? Results from a randomized effectiveness trial.

Depress Anxiety 2007;24(6):392-8.

[41] Grace R, Shenfield G, Tennant C. Cannabis and psychosis in acute

psychiatric admissions. Drug Alcohol Rev 2000;19(3):287-90.

[42] Drake RE, Osher FC, Wallach MA. Homelessness and dual diagnosis.

Am Psychol 1991;46(11):1149-58.

[43] Bartels SJ, Teague GB, Drake RE, Clark RE, Bush PW, Noordsy DL.Substance abuse in schizophrenia: service utilization and costs. J Nerv

Ment Dis 1993;181(4):227-32.

[44] Khantzian EJ. The self-medication hypothesis of substance use

disorders: a reconsideration and recent applications. Harv Rev

Psychiatry 1997;4(5):231-44.

[45] Leweke FM, Koethe D. Cannabis and psychiatric disorders: it is not

only addiction. Addict Biol 2008;13(2):264-75.

[46] Fazel S, Baillargeon J. The health of prisoners. Lancet 2011;

377(9769):956-65.

[47] Lynskey MT, Heath AC, Bucholz KK, Slutske WS, Madden PA,

Nelson EC, et al. Escalation of drug use in early-onset cannabis users

vs co-twin controls. JAMA 2003;289(4):427-33.

[48] Agosti V, Nunes E, Levin F. Rates of psychiatric comorbidity among

US residents with lifetime cannabis dependence. Am J Drug Alcohol

Abuse 2002;28(4):645-54.[49] Grucza RA, Abbacchi AM, Przybeck TR, Gfroerer JC. Discrepancies

in estimates of prevalence and correlates of substance use and disorders

between two national surveys. Addiction 2007;102(4):623-9.


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