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http://bmj.bmjjournals.com/cgi/content/full/325/7374/1195?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=cannabis&andorexactfulltext=and&searchid=1095093886938_14360&stored_search=&FIRSTINDEX=0&sortspec=relevance&resourcetype=1

Cannabis use and mental health in young people: cohort study
Papers pp 1199, 1212
George C Patton, professor of adolescent health a, Carolyn Coffey,
epidemiologist a, John B Carlin, director of unit b, Louisa Degenhardt,
research fellow c, Michael Lynskey, visiting research fellow d, Wayne Hall,
professor of bioethics e.
a Centre for Adolescent Health, Murdoch Children's Research Institute,
Parkville, Victoria 3052, Australia, b Clinical Epidemiology and
Biostatistics Unit, Murdoch Children's Research Institute, c National Drug
and Alcohol Research Centre, University of New South Wales, Sydney 2052,
Australia, d Department of Psychiatry, Washington University School of
Medicine, St Louis, MO 63110, USA, e Office of Public Policy and Ethics,
Institute for Molecular Bioscience, University of Queensland, Brisbane 4072,
Australia
Correspondence to: G Patton gpatton@cryptic.rch.unimelb.edu.au


Objective: To determine whether cannabis use in adolescence predisposes to
higher rates of depression and anxiety in young adulthood.

Design: Seven wave cohort study over six years.

Setting: 44 schools in the Australian state of Victoria.

Participants: A statewide secondary school sample of 1601 students aged
14-15 followed for seven years.
Main outcome measure: Interview measure of depression and anxiety (revised
clinical interview schedule) at wave 7.
Results: Some 60% of participants had used cannabis by the age of 20; 7%
were daily users at that point. Daily use in young women was associated with
an over fivefold increase in the odds of reporting a state of depression and
anxiety after adjustment for intercurrent use of other substances (odds
ratio 5.6, 95% confidence interval 2.6 to 12). Weekly or more frequent
cannabis use in teenagers predicted an approximately twofold increase in
risk for later depression and anxiety (1.9, 1.1 to 3.3) after adjustment for
potential baseline confounders. In contrast, depression and anxiety in
teenagers predicted neither later weekly nor daily cannabis use.

Conclusions: Frequent cannabis use in teenage girls predicts later
depression and anxiety, with daily users carrying the highest risk. Given
recent increasing levels of cannabis use, measures to reduce frequent and
heavy recreational use seem warranted.

What is already known on this topic

Frequent recreational use of cannabis has been linked to high rates of
depression and anxiety in cross sectional surveys and studies of long term
users

Why cannabis users have higher rates of depression and anxiety is uncertain

Previous longitudinal studies of cannabis use in youth have not analysed
associations with frequent cannabis use
What this study adds

A strong association between daily use of cannabis and depression and
anxiety in young women persists after adjustment for intercurrent use of
other substances

Frequent cannabis use in teenage girls predicts later higher rates of
depression and anxiety

Depression and anxiety in teenagers do not predict later cannabis use; self
medication is therefore unlikely to be the reason for the association

After increases in cannabis use during the early 1990s, a majority of young
people in the United Kingdom, United States, New Zealand, and Australia now
use cannabis recreationally. 1 2 Despite the high prevalence of cannabis
use, uncertainty persists about its physical and psychological
consequences.3

Among the most prominent concerns have been putative links between use of
cannabis and mental disorders. A large intake of cannabis seems able to
trigger acute psychotic episodes and may worsen outcomes in established
psychosis. 4 5 Associations with non-psychotic disorders have received less
attention. Yet evidence for an association between cannabis use and
depression and anxiety has grown.6 Chronic daily users report high levels of
anxiety, depression, fatigue, and their motivation is low.7 In one recent
survey of young adults, over a third reported symptoms of anxiety that were
associated with cannabis use; young women reported these more commonly.8
Cross sectional associations between cannabis use and depression and anxiety
have now been reported in surveys in both adolescents and adults, 9 10
although not all studies have found an association in male participants.11

Questions remain about the level of association between cannabis use and
depression and anxiety and about the mechanism underpinning the link.
Pre-existing symptoms might raise the likelihood of cannabis use through a
mechanism of self medication.12 Alternatively, cannabis use may be more
likely in people with a background of social adversity or particular
characteristicsfactors that might also raise risks for mental disorders.
Cannabis may also carry a direct risk for depression and anxiety.

We examined the risks for later depression and anxiety associated with
cannabis use in teenagers. Specifically, the study addressed three
questions. Firstly, does cannabis use in adolescents predict the development
of symptoms of depression and anxiety in young adults? Secondly, do symptoms
of depression and anxiety in adolescence predict cannabis use in young
adults? Thirdly, is any relation explained by factors such as family
background or intercurrent use of other substances?


Between August 1992 and December 1998 we conducted a seven wave cohort study
of adolescent health in the Australian state of Victoria. The cohort was
defined in a two stage cluster sample, in which we selected two classes at
random from each of 44 schools drawn from a stratified frame of government
run, Catholic, and independent schools (total number of students 60 905).
School retention rates to year nine in the year of sampling were 98%. One
class from each school entered the cohort in the latter part of the ninth
school year (wave 1) and the second class six months later, early in the
10th school year (wave 2). Participants were subsequently reviewed at six
month intervals for the next two years (waves 3 to 6), with a final follow
up (wave 7) at the age of 20-21, three years after the final school year in
Victoria. In waves 1 to 6, participants self administered the questionnaire
on laptop computers,13 and those absent from school were followed up by
telephone. The seventh wave of data collection used computer assisted
telephone interviews. All stages of the study were approved by the ethics
committee of the Royal Children's Hospital.

From a total sample of 2032 students, 1947 (95.8%) participated at least
once during the first six (adolescent) waves. In wave 7, 1601 young adults
(79% of the initial sample or 82% of teenage participants) were interviewed
between April and December 1998. Response rates are shown in figure 1.
Reasons for non-completion at follow up were refusal (n=152), loss of
contact (n=192), and death (n=2). We examined characteristics of
non-completers in a logistic regression model. Male participants were
over-represented (odds ratio 1.9, 95% confidence interval 1.5 to 2.4), as
were parental divorce or separation (1.8, 1.4 to 2.5), and daily tobacco
smoking at study inception (2.1, 1.5 to 2.9). Neither teenage depression and
anxiety nor cannabis use were independently associated with loss to follow
up. The mean age at wave 1 was 14.5 (SD 0.5) years; at wave 7 it was 20.7
(0.5) years. Of the 1601 participants in wave 7, 1130 (71%) still lived at
home, 429 (27%) lived with others, and 42 (3%) lived alone. A total of 1345
(82%) had completed the final year of school; 1355 (85%) had started
post-school study.



Measures
We used the computerised revised clinical interview schedule (CIS-R) to
assess depression and anxiety at each wave.14 The schedule provides data on
the frequency, severity, persistence, and intrusiveness of 14 common
psychiatric symptoms and has been widely used in population based surveys.15
A total score of 12 or greater was taken to define a mixed state of
depression and anxiety at a lower threshold than syndromes of major
depression and anxiety disorder but one where clinical intervention would
still be appropriate.16

We assessed cannabis use on the basis of self reported frequency of use in
the previous six months in waves 1 to 6 and in the previous 12 months in
wave 7. This allowed classification as never used, less than weekly use, at
least weekly use, and daily use (defined as using on five or more days per
week), and initiation after wave 6. We assessed use of alcohol, tobacco, and
other illicit drugs (including ecstasy, heroin, amphetamines, LSD, and
steroids) on the basis of self reported frequency of use and with
retrospective diaries over seven days for participants reporting recent
drinking or smoking. Participants drinking on three or more days in the
previous week were classified as frequent drinkers. We assessed antisocial
behaviour in waves 1 to 6 by using items from the self reported early
delinquency scale that covered property damage, interpersonal violence, and
theft.17

Analysis
We collected data at a developmental point when young people are difficult
to trace because of high mobility. Although the response rate was high and
attrition low, 70% of respondents missed at least one wave of data
collection, which led to potential bias in summary measures of exposure to
cannabis and mental health problems calculated from the six waves of data
collection among adolescents. To circumvent this, we used multiple
imputation with five complete datasets created by imputation under the
multivariate mixed effects model of Schafer and Yucel, incorporating the
covariates sex, age, rural or urban residence, and parental education
(available for all participants). 18 19 These covariates were strongly
associated with missingness, and the model incorporated a random effects
structure to accommodate correlation within participants over time. We
constructed principal measures by classifying participants according to
whether they fell into categories of interest at least once during wave 1 to
6 (adolescence) and, separately, in wave 7 (young adulthood). Data analysis
was performed with Stata 7. We modelled associations by univariate and
multivariate logistic regression analyses and used Wald tests and related
confidence intervals to assess statistical significance and precision.


Altogether 71 male participants (9.7%, 95% confidence interval 7.5% to 12%)
and 188 (22%, 19% to 25%) of female participants reported depression and
anxiety as young adults (odds ratio 2.6, 1.9 to 3.5). Sixty six per cent
(484/731) of male participants and 52% (448/859) of female participants
reported using cannabis at some time (11 participants did not respond to
this question), with three quarters starting use when they were teenagers.
Twenty per cent (146; 17% to 22%) of male participants and 8% (69; 6% to
10%) of female participants were using cannabis at least weekly, with 10%
(73; 8% to 12%) of young men and 4% (37; 3% to 6%) of young women using it
daily.

The prevalence of depression and anxiety increased with higher extents of
cannabis use, but this pattern was clearest in female participants (table
1). We used logistic regression to analyse the level of association between
depression and anxiety and cannabis use in young adults (table 2) after
adjustment for concurrent substance use. We found a significant interaction
between sex and daily cannabis use. In the adjusted model, young women who
used cannabis daily had an over fivefold increase in the odds of depression
and anxiety found in non-users.


Cannabis in adolescence and depression in young adults
We used logistic regression to examine the prediction of depression and
anxiety in young adults by cannabis use in adolescence. In the univariate
analysis a dose response was evident: daily use in female teenagers
predicted fourfold higher odds of later depression and anxiety (odds ratio
4.2, 1.6 to 11), weekly use a twofold elevation (2.3, 1.3 to 4.2). In the
multivariate model we collapsed the top categories of cannabis use (table
3). The interaction between sex and weekly or more frequent use was
significant. An almost twofold increase in risk for weekly or more frequent
users who were female persisted after adjustment for potential confounders.
We considered whether depression and anxiety in adolescence predicted later
cannabis use in young adulthood in two further logistic regression models,
examining the predictions of weekly and daily use (table 4). After
adjustment for adolescent cannabis use and other potential confounders,
adolescent depression and anxiety predicted neither weekly nor daily use.


Around 60% of the statewide secondary school sample had used cannabis
recreationally by young adulthood; most participants first experimented
while at secondary school. By young adulthood 7% were daily users and in
young women this level of use was associated with over five times the odds
of depression and anxiety found in non-users. In young women, weekly use as
teenagers predicted a twofold increase in later depression and anxiety and
daily use a fourfold increase. In contrast, depression in teenagers did not
predict higher cannabis use.

Strengths
Earlier cohort studies had a limited capacity to address the key questions
of this study. One study reported a prospective relation between cannabis
use and later depression but started well after the risk period of onset for
both.20 Two important studies in adolescence examined either monthly
cannabis use or use in the preceding yeardoses that in the light of this
study are unlikely to be associated with mental health problems. 21 22

Our close to representative sample, high rates of participation, and
frequent measures during participants' teenage years are strengths of this
study. A telephone interview strategy was used in data collection in the
last wave, and, although prevalence estimates may vary slightly as a result,
it is unlikely to have caused a systematic bias in patterns of association.
The use of multiple imputation minimised measurement biases arising from
missing data during the teenage years, but we did not attempt to adjust for
differential participation of young adults. Even though depression and
anxiety in teenagers and cannabis use did not predict dropout from the
study, the difference in non-responders on other factors (for example, sex
or family structure) may have had some bearing on the specification of
associations.

What the results might mean

Possible explanations for the high degree of depression and anxiety found in
young women who used cannabis often include underlying characteristics that
predispose to both anxiety and depression, self medication of pre-existing
depressive symptoms, and an adverse effect of cannabis on mental health.21
The association with cannabis use persisted after adjustment for concurrent
use of alcohol, tobacco, and other illicit substances as well as indices of
family disadvantagefindings consistent with a more direct relation. We
considered self medication with cannabis but found no prospective relation
between depression and anxiety in adolescence and later frequent cannabis
use, consistent with an earlier report.22
The persistence of associations in the multivariate models and the evidence
for a prospective dose-response relation are consistent with a view that
frequent use of cannabis in young people increases the risks of later
depression and anxiety. Psychosocial mechanismsfor example, the adoption of
a countercultural lifestylepossibly underlie the association. Social
consequences of frequent use include educational failure, dropout,
unemployment, and crimeall factors that may lead to higher rates of mental
disorders. Because risks seem confined largely to daily users, however, the
question about a direct pharmacological effect remains. Cannabinoid
receptors (CB1) are found widely in the central nervous system, with a
distribution that is consistent with effects on a wide range of brain
functions including memory, emotion, cognition, and movement.23

Cannabis use in young people remains a controversial area, and absence of
good data has handicapped the development of rational public health
policies.3 These findings contribute to evidence that frequent cannabis use
may have a deleterious effect on mental health beyond a risk for psychotic
symptoms. Strategies to reduce frequent use of cannabis might reduce the
level of mental disorders in young people.


   Acknowledgments

Contributors: GCP was the principal investigator and prepared the
manuscript. CC was the study coordinator and contributed to data analysis
and manuscript preparation. JBC contributed to the data analysis and
manuscript preparation. LD, ML, and WH contributed to the preparation of the
manuscript. GCP is the guarantor.
   Footnotes

Editorial by Rey and Tennant
Funding: National Health and Medical Research Council and Victorian Health
Promotion Foundation.
Competing interests: None declared.

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(Accepted 15 August 2002)



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