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آرشيو موضوعي |
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Cannabis withdrawal in adolescent treatment
seekers
Ryan Vandrey, , Alan J. Budney, Jody
L. Kamon and Catherine Stanger
Department of Psychology and Psychiatry, University of Vermont, 54
W. Twin Oaks Terrace, Suite 12, S. Burlington, VT 05403, USA
Received 9 July 2004; revised 8 November 2004; accepted 10
November 2004. Available online 18 December 2004.
Abstract
A valid cannabis withdrawal syndrome has been
demonstrated in controlled studies with adult marijuana abusers,
yet few published reports have examined cannabis withdrawal
among adolescents. Adolescents presenting for outpatient
substance abuse treatment, whose primary substance of abuse was
cannabis, completed a questionnaire reporting the presence and
severity of withdrawal symptoms during past periods of cannabis
abstinence. Nearly two-thirds of the sample indicated that they
had experienced four or more symptoms, and over one-third
reported four or more symptoms that occurred at a moderate or
greater severity. The magnitude of withdrawal severity was
positively correlated with current emotional and behavioral
symptoms and self-reported problems with cannabis use. These
findings are consistent with previous studies, though the
prevalence and magnitude of withdrawal symptoms were lower than
that observed in a similar study with adult treatment seekers [Budney,
A.J., Novy, P., Hughes, J.R., 1999. Marijuana withdrawal among
adults seeking treatment for marijuana dependence. Addiction 94,
13111322]. Further research is needed to elucidate associations
between cannabis withdrawal effects, the initiation of cessation
attempts, and relapse.
Keywords: Cannabis;
Marijuana; Withdrawal; Adolescent
Article Outline
1. Introduction
Epidemiological studies of drug-use patterns
consistently report that cannabis is the most frequently used
illicit drug in most developed countries (European
Monitoring Center for Drugs and Drug Addiction, 2003,
Hall et al., 1999 and
SAMHSA, 2003). Treatment admissions for marijuana problems
in the U.S. have steadily increased since the mid-1990s and have
become comparable in number to admissions for primary cocaine
and heroin problems (SAMHSA,
2003). Though not recognized as clinically significant in
the DSM and not well defined in the ICD, recent neurobiological,
behavioral, and clinical studies have raised concern about the
potential role of a cannabis withdrawal syndrome in the
development, maintenance, and treatment of chronic cannabis use
and dependence (Budney
et al., 2004 and
Budney and Moore, 2002).
Cannabinoid withdrawal has been reliably
precipitated using the CB1 receptor antagonist SR141716A in
non-human species (Lichtman
and Martin, 2002), and an association has been observed
between cannabinoid withdrawal and cellular alterations in the
limbic system similar to that observed during withdrawal from
other drugs of abuse (deFonseca
et al., 1997). Controlled laboratory studies with humans
have characterized a valid and reliable cannabis withdrawal
syndrome in adult heavy (daily or almost daily) cannabis users (Budney
et al., 2001,
Budney et al., 2003,
Haney et al., 1999 and
Kouri and Pope, 2000). Commonly observed withdrawal symptoms
include anger/aggression, anxiety, decreased appetite/weight
loss, irritability, restlessness, and sleep difficulty.
Depressed mood, stomach pain/physical discomfort, shakiness, and
sweating have also been reported, but occur less frequently.
Most symptoms onset within 24 h of abstinence, peak within the
first week, and last approximately 12 weeks (Budney
et al., 2003 and
Kouri and Pope, 2000).
The majority of adults presenting for
treatment of cannabis dependence report experiencing
cannabis-withdrawal symptoms during periods of abstinence (Budney
et al., 1999,
Copeland et al., 2001,
Stephens et al., 1993 and
Stephens et al., 2002). Only one report, however, provided
information on the incidence and magnitude of specific
withdrawal symptoms in adults seeking treatment for cannabis-use
problems (Budney
et al., 1999). Retrospective reports of specific symptoms
were concordant with those observed in the aforementioned
laboratory studies, with the majority of patients reporting four
or more different symptoms of at least moderate severity.
Unfortunately, much less information on
cannabis withdrawal among adolescent cannabis users is
available. Clinical epidemiological data underscore the
potential importance of cannabis withdrawal among youth. Recent
estimates indicate that 16, 32, and 37% of 8th, 10th, and 12th
graders, respectively, have used cannabis in the previous year,
and among 12th graders who used, approximately 20% report using
cannabis daily (Johnston
et al., 2001). Most importantly, youth aged 20 and under
comprise over half of all treatment admissions for cannabis
abuse in the U.S., and cannabis is reported to be the primary
drug of abuse in the majority of all adolescent substance abuse
admissions (SAMHSA,
2001).
Only a few studies provide empirical data on
cannabis-withdrawal symptoms among youth. Past cannabis
withdrawal was endorsed by 15% of adolescents in a
community-based sample that met DSM-IV criteria for either
cannabis abuse or dependence (Young
et al., 2002). Among adolescents enrolled in a residential
treatment program for conduct disordered substance users, 79%
met DSM-III-R criteria for cannabis dependence and 67% of those
reported experiencing cannabis withdrawal during prior quit
attempts (Crowley
et al., 1998). In a similar study of conduct-disordered,
substance abusing adolescents enrolled in residential or day
treatment, approximately 40% met criterion for cannabis
withdrawal as assessed using CIDI-SAM interviews (Mikulich
et al., 2001). In the two studies that assessed the
occurrence of specific withdrawal symptoms, anxiety,
restlessness, irritability, trouble concentrating, appetite
changes, depression, sleep difficulty, feeling tired or weak,
and yawning were most commonly endorsed (Crowley
et al., 1998 and
Mikulich et al., 2001). Last, a clinical case report on
three adolescents with daily cannabis-use enrolled in outpatient
treatment described similar withdrawal symptoms (Duffy
and Milin, 1996).
The present study assessed the prevalence and
magnitude of cannabis-withdrawal symptoms in adolescents
presenting for outpatient treatment of substance abuse where
cannabis was identified as the primary substance being used. As
with our initial study on cannabis withdrawal in adult marijuana
abusers (Budney
et al., 1999), this study relies on retrospective reports of
symptoms that occurred during prior periods of abstinence from
cannabis. In addition to describing the withdrawal symptom
profile, exploratory, correlation analyses were conducted to
examine potential predictors of withdrawal such as age, cannabis
problem severity, and psychiatric symptomatology. Based on our
findings with adults (Budney
et al., 1999), we expected positive correlations between
withdrawal, cannabis problem severity, and psychiatric
symptomology. Results extend previous research by systematically
examining the cannabis-withdrawal syndrome in an outpatient
sample with psychosocial characteristics typical of the majority
of adolescents who enter outpatient treatment for cannabis abuse
or dependence.
2. Methods
2.1. Participants
Participants were adolescents seeking
outpatient treatment for substance abuse problems at the
University of Vermont Treatment Research Center in Burlington,
Vermont. Inclusion for this study required that cannabis was the
primary drug of abuse, and that the self-reported usual pattern
of cannabis-use was at least 15 days of use per month for at
least one of the 3 months prior to intake. Patients concurrently
dependent on a second drug other than tobacco, or exhibiting
severe psychiatric problems (e.g. active psychosis or acute high
risk of suicide) were excluded.
Of the 138 adolescents presenting for
treatment, 72 (52%) met the above criteria. Sixty-two (45%) were
excluded because they reported using cannabis on fewer than 15
days per month, and 4 (3%) were excluded because they met DSM-IV
dependence criteria for alcohol or an illicit drug of abuse. Of
the 72 participants that met criteria, 19 were enrolled in a
4-week fee-for-service, brief assessment and intervention
program for adolescent substance abuse, and 53 were enrolled in
a 14-week clinical trial that targeted adolescents (18 and
under) with cannabis-use problems.
Participants were between 14 and 19 years old
(M = 16.2, S.D. = 1.1 years), and primarily male (90%) and
Caucasian (89%) (see
Table 1). The homogeneity of this sample is consistent with
reports of greater substance abuse and treatment admissions in
males in the U.S. (SAMHSA,
2003), and reflects the ethnic composition of the community
in which the study was conducted (Vermont
Department of Health, 2002). Participants reported using
cannabis on a mean of 18.1 (S.D. = 7.8) of the 30 days prior to
the intake assessment, smoking cannabis on average 3.5
(S.D. = 2.6) times on those days. Fifty-seven and thirty-one
percent met DSM-IV criteria for current cannabis dependence and
abuse, respectively. Sixty-one percent reported being current
tobacco smokers and approximately half (49%) reported use of
alcohol at least once in the month prior to treatment intake.
Participant self-report and urine drug testing suggest that use
of other illicit drugs was infrequent. One participant tested
positive for cocaine and a second participant tested positive
for opiates at intake
Table 1.
Participant characteristics (N = 72)
|
Demographics |
|
Mean age (years) |
16.2 ± 1.1 |
|
Percent male |
90 |
|
Percent Caucasian |
89 |
|
|
Substance use |
|
DSM-IV cannabis dependence (%) |
57 |
|
DSM-IV cannabis abuse (%) |
31 |
|
Days cannabis use (past 30) |
18.1 ± 7.8 |
|
Used tobacco (past month) (%) |
61 |
|
Used alcohol (past month) (%) |
49 |
|
|
Cannabis-related problems |
|
MPI score |
8.8 ± 7.2 |
|
Withdrawal discomfort score |
9.9 ± 9.6 |
|
|
Psychiatric symptoms |
|
YSR externalizing scale |
59.8 ± 10.4 |
|
Percent in clinical range (%) |
39 |
|
YSR internalizing scale |
51.5 ± 12.4 |
|
Percent in clinical range (%) |
16 |
Scores reflect sample mean and standard
deviation (S.D.) for specified measures. YSR scale scores
reflect t-scores and clinical range is defined as
scores in the 90th percentile (t-scores ≥ 63).
2.2. Measures
Data were collected during a 23-h intake
assessment. Written informed consent was obtained from all
participants. Substance-use behavior and dependence were
measured via self-report questionnaires and interviews. The
Daily Marijuana Questionnaire (DMQ) was adapted from the Daily
Drinking Questionnaire (Dimeff
et al., 1999) and is a self-report measure of the frequency,
quantity, and pattern of cannabis-use during the 3 months prior
to intake. A general drug history interview was used to
corroborate cannabis-use as assessed by the DMQ, and to assess
recent use of alcohol, tobacco, and other illicit drugs. The
Marijuana Problem Inventory (MPI), a 23-item questionnaire
adapted from the Rutgers Alcohol Problem Index (RAPI) (White
and Labouvie, 1989), assessed the number of problem
behaviors associated with use of cannabis in the 3 months prior
to intake. The MPI had high internal reliability (Cronbach's
alpha = 0.94). Substance-use disorders were assessed using the
Vermont Structured Diagnostic Interview modified for the
Diagnostic and Statistical Manual of Mental Disorders, 4th
edition (Hudziak
et al., 1993).
A 15-item version of the Marijuana Withdrawal
Checklist (MWC) (Budney
et al., 1999) lists common as well as less frequently
observed cannabis-withdrawal symptoms (items: craving for
marijuana, depressed mood, decreased appetite, increased
aggression, increased anger, headache, irritability, nausea,
nervousness/anxiety, restlessness, shakiness, sleep difficulty,
stomach pains, strange dreams, and sweating). Participants rated
each item on a 03 scale (0 = not at all, 1 = mild,
2 = moderate, and 3 = severe) based on their experience the last
time they stopped using cannabis. A composite withdrawal
discomfort score (WDS) was created by summing the severity
ratings of all 15 items. The internal reliability of this
measure was high (Cronbach's alpha = 0.92), and is comparable to
that observed in our previous studies (range 0.810.89). The
sensitivity of the MWC to cannabis abstinence effects in our
prior laboratory research suggests it is a valid measure of
withdrawal.
The Youth Self-Report (YSR) (Achenbach
and Rescorla, 2001) assessed emotional and behavioral
problems. The YSR has three broad problem scales, externalizing,
internalizing, and total problems, and eight specific syndrome
scales. For brevity, only the externalizing and internalizing
scales are included here. The externalizing problems scale
includes items concerning rule-breaking and aggressive
behaviors, and the internalizing problems scale includes items
concerning anxiety, depression, withdrawn behaviors, and somatic
complaints. Scores above the 90th percentile denote clinical
significance.
2.3. Data analyses
Data collected using the measures described above were double
entered and checked for accuracy. The primary analyses comprise
descriptive statistics regarding the prevalence and severity of
withdrawal symptoms reported on the MWC. Secondary analyses
included a one-way analysis of variance comparing those who met
cannabis dependence criteria at intake (N = 41) and those
who did not (N = 30) on the WDS. One participant was
excluded from this analysis due to missing data on cannabis
dependence. Correlation analyses were also performed to explore
associations among withdrawal symptoms, and relations between
WDS, internalizing and externalizing problem scores, frequency
of cannabis-use, MPI score, and age. The distribution of scores
was reasonably normal for variables other than the individual
MWC items, and thus parametric tests were performed. Due to the
limited range of values (03) and skewed distribution of
individual MWC item scores, Spearman's rank correlations were
used to calculate the inter-item correlations of the MWC. Note
that one item on the MPI asks specifically about withdrawal
symptoms, and was therefore excluded from computation of the MPI
score.
3. Results
3.1. Prevalence and severity
Participants reported an average of 5.3
(S.D. = 4.1) discrete symptoms from the MWC of at least mild
severity. Seventy-eight percent reported two or more symptoms,
58% reported four or more symptoms, and 44% reported six or more
symptoms (Fig.
1). The most commonly reported symptoms were craving for
marijuana, depressed mood, irritability, restlessness, sleep
difficulty, increased anger, decreased appetite, increased
aggression, nervousness/anxiety, and headache (Table
2). Four of these symptoms (craving for marijuana, depressed
mood, irritability, and sleep difficulty) were rated as being of
moderate severity or greater by at least 30% of the sample.
Fig. 1. The percentage of participants
reporting at least 2, 4, 6, or 8 different MWC items are
shown, separated by the minimum rating of symptom severity
for each symptom in the cluster.
Table 2.
Percentage of participants who reported each MWC item by
severity rating
|
Mild rating ≥ 1
|
Moderate rating ≥ 2
|
Severe rating ≥ 3
|
|
Mood |
|
Depressed mood |
58 |
31 |
13 |
|
Irritability |
47 |
32 |
18 |
|
Increased anger |
40 |
21 |
10 |
|
Nervousness/anxiety |
33 |
19 |
13 |
|
|
Behavioral |
|
Craving |
71 |
46 |
28 |
|
Restlessness |
46 |
26 |
10 |
|
Sleep difficulty |
43 |
31 |
13 |
|
Decreased appetite |
39 |
21 |
6 |
|
Increased aggression |
36 |
19 |
8 |
|
Strange dreams |
26 |
15 |
8 |
|
|
Physical |
|
Headache |
32 |
18 |
7 |
|
Shakiness |
29 |
14 |
6 |
|
Sweating |
19 |
11 |
3 |
|
Stomach pains |
18 |
7 |
4 |
|
Nausea |
15 |
8 |
1 |
3.2. Secondary analyses
WDS scores for adolescents meeting criteria
for cannabis dependence (M = 13.2, S.D. = 9.8) were
significantly greater (F(1, 69) = 15.9, P < .01)
than those not meeting dependence criteria (M = 4.9,
S.D. = 6.9). The 10 most frequently reported withdrawal symptoms
were moderately correlated with each other (range = 0.310.75;
P < .01), except for the correlations between craving and
nervousness/anxiety, decreased appetite and headache, and
headache and nervousness/anxiety (Table
3). An insufficient sample size precluded factor analysis to
further identify discrete subgroups of related symptom
expression (e.g. affective, behavioral, etc.).
Table 3.
Correlations among the 10 most frequently reported
withdrawal symptoms
|
Craving
|
Appetite
|
Depress
|
Irritable
|
Headache
|
Aggress
|
Anger
|
Ner/Anx
|
Restless
|
Sleep
|
|
Craving |
*** |
0.34* |
0.42* |
0.53* |
0.34* |
0.37* |
0.34* |
0.17 |
0.52* |
0.62* |
|
Decreased appetite |
|
*** |
0.56* |
0.51* |
0.29* |
0.56* |
0.54* |
0.38* |
0.59* |
0.49* |
|
Depressed mood |
|
|
*** |
0.63* |
0.41* |
0.42* |
0.41* |
0.40* |
0.62* |
0.47* |
|
Irritability |
|
|
|
*** |
0.37* |
0.60* |
0.55* |
0.41* |
0.66* |
0.58* |
|
Headaches |
|
|
|
|
*** |
0.34* |
0.50* |
0.26 |
0.55* |
0.44* |
|
Increased aggression |
|
|
|
|
|
*** |
0.75* |
0.48* |
0.49* |
0.42* |
|
Increased anger |
|
|
|
|
|
|
*** |
0.31* |
0.55* |
0.52* |
|
Nervousness/anxiety |
|
|
|
|
|
|
|
*** |
0.55* |
0.37* |
|
Restlessness |
|
|
|
|
|
|
|
|
*** |
0.69* |
|
Sleep difficulty |
|
|
|
|
|
|
|
|
|
*** |
* Spearman's correlation coefficients significant
at P < 0.01.
Correlations between the WDS and
internalizing and externalizing scales of the YSR, days of
cannabis-use in the past 30, total problems on MPI, and age are
presented in
Table 4. Internalizing and externalizing scores from the YSR
and total MPI score showed significant positive correlations
with the WDS (r = 0.60, 0.45, and 0.59, respectively; all
P < .01).
Table 4.
Correlations between withdrawal discomfort score (WDS)
and baseline variables
|
Age |
0.01 |
|
Days cannabis use |
−0.02 |
|
MPI score |
0.59* |
|
YSR externalizing |
0.45* |
|
YSR internalizing |
0.60* |
* Pearson's correlation coefficients significant
at P < 0.01.
4. Discussion
This study indicates that many
cannabis-abusing adolescents who present for outpatient
substance abuse treatment report experiencing numerous symptoms
when they discontinue using cannabis. The most common symptoms
reported were affective and behavioral in nature, although a
subset of adolescents also experienced physical symptoms (e.g.
headache, nausea, sweating). These findings are consistent with
prior reports of cannabis withdrawal in clinical samples. In
both the current study and earlier reports on behaviorally
disordered adolescents in either residential or day treatments (Crowley
et al., 1998 and
Mikulich et al., 2001), anxiety, appetite change, depressed
mood, irritability, and restlessness were among the most
commonly reported symptoms. Comparing the present findings with
those in our prior study of adult treatment seekers (Budney
et al., 1999), six out of the seven most frequently reported
symptoms were shared across samples (craving, depressed mood,
increased anger, irritability, restlessness, and sleep
difficulty).
One noteworthy difference between withdrawal
symptom reports in the current adolescent sample and the adult
clinical sample (Budney
et al., 1999) was that the incidence and magnitude of
symptoms was substantially lower in the adolescent sample. For
example, the prevalence of craving, depressed mood,
irritability, and restlessness in the adolescent sample was 71,
58, 47, and 46%, respectively, compared with 93, 76, 87, and 76%
in the adult sample. Also, in the adolescent sample, only
ratings of craving were reported as severe by more than 20% of
participants, compared with six symptoms (anger, craving,
depression, irritability, nervousness, and restlessness) in the
adult sample. These differences are likely due to the generally
less frequent cannabis use in the adolescent sample compared to
the adult sample. Only 32% of the adolescents used cannabis
daily in the month prior to intake compared with 82% of the
adults.
These findings must be interpreted with
caution due to several methodological limitations. First,
symptom reports were collected retrospectively, thus, responses
were subject to memory and attribution biases. Second,
concurrent abstinence from other substances during the referent
period of abstinence from cannabis was not controlled. Note,
however, that abuse of other drugs was relatively uncommon in
this sample, and participants dependent on substances other than
cannabis were excluded. Nonetheless, many reported past use of
other illicit drugs and over half were current tobacco users,
hence the influence of other drug abstinence effects on the
symptom reports cannot be ruled out. That said, we believe the
validity of these symptom reports is good based on the high
degree of correspondence with symptom data collected in the
parallel study of adults using the same methodology and
laboratory studies examining cannabis withdrawal under
controlled conditions (Budney
et al., 2004).
Keeping these limitations in mind, nearly
two-thirds of the sample reported four or more withdrawal
symptoms, and over one-third reported four or more that occurred
at moderate or greater severity. Note that in the most recent
edition of the DSM, between two and four symptoms are needed to
meet criteria for the various substance withdrawal disorders (American
Psychiatric Association, 2000). Given the prevalence and
magnitude of these symptoms, it is conceivable and concerning
that a withdrawal syndrome could contribute to continued use of
cannabis and negatively impact cessation attempts among
adolescents who use cannabis regularly.
The present study replicated the positive
correlation between emotional and behavioral symptoms and
withdrawal severity observed in our initial study with adult
treatment seekers (Budney
et al., 1999). Whether this association reflects an overlap
of common symptom reporting in persons with existing psychiatric
symptomatology, or indicates that existing psychiatric symptoms
exacerbate withdrawal severity is not clear. Similar
associations have been observed in tobacco users showing that
anxiety, depression, and disordered eating are associated with
increased severity of nicotine-withdrawal symptoms (Pomerleau
et al., 2000). Prior controlled laboratory studies with
adult cannabis users show that such behavioral and emotional
symptoms increase in severity during cannabis abstinence
compared with measures of these symptoms under conditions of
continued cannabis use (Budney
et al., 2001 and
Budney et al., 2003). Hence, the symptoms attributed to
cannabis withdrawal in the present sample of adolescents likely
reflect valid indicators of a withdrawal syndrome, and suggest
that cannabis abusing adolescents with more emotional and
behavioral symptoms, like adults with such problems, are apt to
experience more severe discomfort when abstaining from cannabis.
In contrast to expectations, significant
correlations were not observed between withdrawal severity and
age or cannabis use frequency. The failure to observe such
associations may have resulted from the narrow range of both
variables in the present sample. Moreover, we were unable to
control for the time between the interview and the referent
abstinence period or the frequency of cannabis use prior to that
period, which also may have confounded the relation between
these variables. Prospective studies with a larger sample size
and broader range of cannabis use are needed to better
understand these relations. The strong associations between
problem severity (MPI), cannabis dependence, and withdrawal
severity may reflect a tendency to attribute problems to
cannabis use, or it may indicate that those who have more severe
problems or are more severely dependent on cannabis are likely
to experience greater withdrawal. These measures may be useful
indices for predicting cannabis withdrawal symptoms among those
entering treatment.
Significant strides have been made in
characterizing and understanding cannabis withdrawal, however,
many questions remain, especially concerning adolescents. A
prospective examination of withdrawal in adolescent cannabis
users would further establish the reliability and validity of
the extant findings. Moreover, studies examining the impact of
cannabis withdrawal on cessation attempts are clearly needed, as
well as those that evaluate whether treatments targeting
cannabis withdrawal enhance treatment outcome.
Acknowledgements
This research was supported by grants DA15186, DA12471, and
T32-DA07242 from the National Institute on Drug Abuse.
Preliminary findings from this article were presented at the
Annual Convention of the American Psychological Association,
August 2003, Toronto, Ont., Canada.
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