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Marijuana Abstinence Effects in Marijuana Smokers Maintained in Their Home Environment
Alan J. Budney, PhD;
John R. Hughes, MD;
Brent A. Moore, PhD;
Pam L. Novy, PhD
Arch Gen Psychiatry. 2001;58:917-924.
ABSTRACT
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Background Although withdrawal symptoms are commonly reported by persons seeking
treatment for marijuana dependence, the validity and clinical significance
of a marijuana withdrawal syndrome has not been established. This controlled
outpatient study examined the reliability and specificity of the abstinence
effects that occur when daily marijuana users abruptly stop smoking marijuana.
Methods Twelve daily marijuana smokers were assessed on 16 consecutive days
during which they smoked marijuana as usual (days 1-5), abstained from smoking
marijuana (days 6-8), returned to smoking marijuana (days 9-13), and again
abstained from smoking marijuana (days 14-16).
Results An overall measure of withdrawal discomfort increased significantly
during the abstinence phases and returned to baseline when marijuana smoking
resumed. Craving for marijuana, decreased appetite, sleep difficulty, and
weight loss reliably changed across the smoking and abstinence phases. Aggression,
anger, irritability, restlessness, and strange dreams increased significantly
during one abstinence phase, but not the other. Collateral observers confirmed
participant reports of these symptoms.
Conclusions This study validated several specific effects of marijuana abstinence
in heavy marijuana users, and showed they were reliable and clinically significant.
These withdrawal effects appear similar in type and magnitude to those observed
in studies of nicotine withdrawal.
INTRODUCTION
MARIJUANA smoking remains the most prevalent form of illicit drug use
in the United States.1 Treatment seeking for
marijuana dependence increased during the 1990s.2
Controlled trials3, 4, 5
evaluating treatments for marijuana dependence suggest that initiating and
maintaining marijuana abstinence, like with other drug dependencies, is difficult.
Whether an aversive withdrawal syndrome contributes to this difficulty is
unclear.
Nonhuman studies of cessation of marijuana or cannabinoids have provided
evidence of a withdrawal response. In rhesus monkeys, withdrawal occurred
following cessation of injected and oral tetrahydrocannabinol (THC) administration.6, 7 Recent antagonist challenge studies8, 9 have demonstrated a marked precipitated
cannabinoid withdrawal syndrome in rats and dogs.
Early inpatient laboratory studies10, 11, 12
confirmed the animal research. Cessation following the administration of marijuana
cigarettes or oral THC produced decreased appetite, irritability, restlessness,
sleep difficulties, and uncooperativeness. Two recent placebo-controlled inpatient
studies13, 14 extended these findings
by examining abstinence effects following moderate dosing of oral THC or smoked
marijuana. Both studies demonstrated withdrawal effects that included anxiety,
decreased contentment and food intake, depressed mood, irritability, restlessness,
sleep difficulty, and stomach pain.
The abstinence effects reported in the inpatient laboratory studies
were less severe than were retrospective reports15
of withdrawal in marijuana-dependent outpatients. One explanation for this
may be that inpatient studies do not include environmental stimuli that can
produce conditioned withdrawal effects (eg, persons or things associated with
smoking).16, 17 A recent outpatient
study18 of daily marijuana smokers reported
increased anxiety, irritability, physical symptoms, negative mood, and decreased
appetite during 28 days of abstinence, but the magnitude of these symptoms
was difficult to discern because retrospective reports were used for the baseline
assessment.
Marijuana withdrawal is not recognized in the DSM-IV,19 as it concludes that the clinical
significance of the syndrome has yet to be established. A recent study15 indicated that most individuals seeking treatment
for marijuana dependence report a withdrawal syndrome of substantial severity.
Given the reliance on retrospective reports of withdrawal symptoms and the
lack of baseline measures in that study, better-controlled outpatient studies
to determine the validity and significance of a marijuana withdrawal syndrome
are indicated.
The present study systematically examined the reliability and validity
of abstinence effects following cessation of heavy marijuana use in an outpatient
environment. Observation of marijuana users in their natural living environment
during periods of regular marijuana use and abstinence should provide a more
accurate evaluation of the magnitude and significance of the effects that
occur when heavy marijuana use is discontinued.
PARTICIPANTS AND METHODS
PARTICIPANTS
Seven male and 5 female (10 white and 2 Native American) volunteers,
ranging in age from 18 to 50 years (mean ± SD, 30.1 ± 9.0 years),
completed a 16-day outpatient study. Participants were recruited via newspaper
advertisements seeking regular marijuana users for a nontreatment study on
the effects of marijuana use. Participants had to report using marijuana at
least 25 days per month during the previous 6 months, and experiencing at
least 2 withdrawal symptoms during previous periods of cessation. Individuals
were excluded if they met the DSM-IV criteria for
an Axis I psychiatric disorder, including substance use disorders other than
marijuana, nicotine, or caffeine dependence; used any illicit substances other
than marijuana during the previous 30 days; were taking psychotropic medication;
were pregnant; or were seeking treatment for marijuana-related problems. Approximately
25% of those who responded to the advertisements were eligible to participate.
Most exclusions were for use of psychiatric medication or illicit drugs other
than marijuana.
Participants were all regular heavy marijuana users. The mean ±
SD age at first use was 15.4 ± 2.2 years, and the mean ± SD
years of regular use was 13.7 ± 8.9 years. Subjects were primarily
daily smokers (mean ± SD, 28.5 ± 2.8 days in the past month)
who smoked multiple times per day (mean ± SD, 3.3 ± 1.3 episodes
per day). Eleven participants (92%) met the DSM-IV
criteria for marijuana dependence or abuse. Of the 12 participants, 3 were
regular tobacco cigarette smokers.
MEASURES
The timeline follow-back method20 assessed
daily licit and illicit substance use during the prior 30 days. A drug history
questionnaire assessed use of marijuana and other drugs. The DSM-IV Checklist21 was used to diagnose
Axis I psychiatric disorders.
Each study day, participants completed the substance use diary, the
Marijuana Withdrawal Checklist (MWC), the Brief Symptom Inventory, the Marijuana
Craving Questionnaire, the Sleep Inventory, and the Profile of Mood States
scale. The MWC comprises 27 symptoms for which participants indicate severity
during the prior 24 hours on a 4-point scale (0 indicates not at all; 1, mild;
2, moderate; and 3, severe). This checklist was modified from a previous version
developed for use in a retrospective study15
of marijuana. To minimize expectancy effects, the MWC was labeled the "Behavior
Checklist." A withdrawal discomfort score (WDS) was computed by summing the
10 MWC items most frequently reported in the prior study15
(anger, craving for marijuana, depressed mood, decreased appetite, headaches,
irritability, nervousness, restlessness, sleep difficulty, and strange dreams).
The internal reliability of the WDS was high ( = .89).
The Marijuana Craving Questionnaire was adapted from a valid tobacco-smoking
urges questionnaire.22 This questionnaire yields
a total craving and 2 subscale scores. Subscale 1 reflects intention and desire
to smoke marijuana and anticipated pleasure, and subscale 2 reflects anticipation
of relief from negative affect and withdrawal.
The Brief Symptom Inventory is a valid measure of psychiatric symptoms
that yields 9 scales (somatization, obsessive-compulsive, interpersonal sensitivity,
depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism).23 The Profile of Mood States scale provides 6 mood
scale scores (tension, depression, anger, vigor, fatigue, and confusion).24 A 5-item Sleep Inventory assessed total amount of
sleep, sleep-onset latency, number of nocturnal awakenings, time of awakening,
and subjective sleep quality (7-point scale).25
At the start of each laboratory visit, heart rate and blood pressure
(sitting) were measured via an automated monitor (DINIMAP; Johnson & Johnson,
Arlington, Tex). Body weight was obtained on a standing mechanical scale (Detecto;
Cardinal Scale Manufacturing Co, Webb City, Mo) without shoes and heavy clothing,
and after a urine specimen was provided.
All participants named a collateral observer with whom they spent at
least 2 hours per day. Each day, a research assistant telephoned the observer
and administered the MWC in reference to the participant's behavior.
PROCEDURES
An ABAB within-subjects design was used. The 16-day outpatient study
included a 5-day baseline (smoking-as-usual) phase 1, a 3-day marijuana abstinence
phase 1, a second 5-day baseline phase 2 (smoking as usual), and a second
3-day marijuana abstinence phase 2. Symptom increases from baseline 1 to abstinence
1 indicated potential marijuana abstinence effects. Symptom decreases during
baseline 2 following abstinence 1 confirmed that such abstinence effects were
related to marijuana use. Symptom increases observed from baseline 2 to abstinence
2 indicated that these effects were reliable.
Study day 1 was scheduled for a Thursday to minimize the effect of specific
days (weekend vs weekday) on symptom ratings. With this schedule, 3 weekdays
were included in each phase of the study. Women with regular menstrual cycles
began on the Thursday following the onset of menses to minimize potential
premenstrual behavioral and mood changes. Participants made 30-minute visits
to the laboratory at the same time each day (4-8 PM). The University of Vermont,
Burlington, institutional review board approved all procedures, and informed
consent was obtained before baseline phase 1.
During baseline 1, participants were requested not to change their usual
pattern of marijuana smoking and to abstain from all psychoactive drugs, with
the exception of alcohol, nicotine, and caffeine. They were instructed not
to make significant changes in their diet or exercise habits. Participants
were also instructed not to smoke marijuana for at least 2 hours before each
visit. At each visit, physiological measures were taken, a urine specimen
was collected, breath alcohol level was determined, and the affective and
behavioral measures were completed.
On the day 5 baseline 1 visit, participants were instructed to abstain
completely from marijuana and to continue with the daily laboratory visits.
During abstinence phase 1, the same information as in baseline 1 was collected.
On day 3 of abstinence 1, participants were asked whether they planned to
resume their usual pattern of marijuana smoking. If they said yes, we asked
if they would participate in the second half of the study. All participants
planned to return to smoking that day and provided consent to continue. Instructions
for baseline 2 and abstinence 2 were identical to those for baseline 1 and
abstinence 1.
Only participants whose urine screen results verified illicit drug abstinence
throughout the study and marijuana abstinence during the abstinence phases
were eligible to continue. A research assistant collected observed urine specimens.
An enzyme-multiplied immunoassay technique tested for the use of drugs other
than marijuana (benzodiazepines, cocaine, methamphetamine, and opioids) (Dade-Behring,
San Jose, Calif). A quantitative analytic procedure was used to determine
marijuana abstinence.26 Gas chromatographic–mass
spectroscopic levels of 11-nor-9-carboxy- 9-THC, the primary marijuana
metabolite, were normalized to the urine creatinine concentration measured
via a modified Jaffe alkaline picrate method to obtain a metabolite-creatinine
ratio. Abstinence was confirmed if the metabolite-creatinine ratio on any
day did not increase by more than 50% from the ratio obtained the previous
day.26
Participants received a total of $525 in 4 payments. Compensation for
participation in the abstinence phases was provided only after urinalysis
results confirmed marijuana abstinence.
DATA ANALYSIS
A series of repeated-measures analyses of variance were performed on
dependent variables across days within each of the 4 phases. The primary analyses
were a priori contrasts (2-tailed) comparing the mean scores of baseline 1
and abstinence 1, abstinence 1 and baseline 2, and baseline 2 and abstinence
2. If significant differences were observed on the planned contrasts, the
day-by-phase interaction term was examined to determine if effects intensified
or dissipated within each 3-day abstinence phase (time-course effects). Significance
levels were not corrected for multiple comparisons, as the ABAB design allowed
for replication of significant effects within the study. Data from weekend
days during the 5-day baseline phases were excluded to provide comparable
3-day weekday segments for each phase. Data are given as mean ± SD
unless otherwise indicated.
RESULTS
MARIJUANA USE AND ABSTINENCE VERIFICATION
During baseline phases 1 and 2, participants smoked marijuana a mean
of 3.9 ± 2.1 and 4.5 ± 2.0 times per day, respectively, and
reported no use of other illicit psychoactive substances. During the abstinence
phases, all subjects reported no use of marijuana or other psychoactive substances.
All urinalysis results for substances other than marijuana were negative,
and breath alcohol levels were all zero. Self-reported abstinence from marijuana
was confirmed in all subjects using the previously mentioned quantitative
procedure. Normalized 11-nor-9-carboxy-9-THC levels obtained during
the abstinence phases differed significantly from levels obtained during the
baseline phases (F1,11 = 13.92, P = .003)
and decreased consistently across days in the abstinence phases (F6,66 = 4.71, P<.001) (Figure 1).
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Figure 1. Mean creatinine–normalized
tetrahydrocannabinol levels are presented across study days (N = 12). MJ indicates
marijuana smoking phase; ABS, marijuana abstinence phase.
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AFFECTIVE AND BEHAVIORAL SYMPTOMS
The WDS significantly increased between baseline 1 and abstinence 1
(F1,33 = 13.57, P<.001, effect size
[d] = 0.87), decreased between abstinence 1 and baseline
2 (F1,33 = 17.92, P<.001, d = 1.00), and increased again between abstinence 2 and baseline 2
(F1,33 = 9.67, P = .004, d = 0.73) (Table 1 and Figure 2). These d
values indicate a medium to large effect according to Cohen.27
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Ratings for the Marijuana Withdrawal Checklist*
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Figure 2. Mean scores for 6 Marijuana Withdrawal
Checklist items and the mean Withdrawal Discomfort score are presented across
study days (N = 12). MJ indicates marijuana smoking phase; ABS, marijuana
abstinence phase.
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Significant differences between mean scores on 6 MWC items (aggression:
F1,33 = 11.91, P = .002; anger: F1,33 = 11.43, P = .002; craving for marijuana:
F1,33 = 13.47, P = .001; decreased appetite:
F1,33 = 7.85, P = .008; irritability:
F1,33 = 6.43, P = .02; and sleep difficulty:
F1,33 = 5.49, P = .03) were observed in
comparisons between baseline 1 and abstinence 1 (Figure 2). The d values for these items
ranged from 0.52 to 0.87.
The 6 items showing significant change from baseline 1 to abstinence
1 all showed significant change back toward baseline values during baseline
2 (aggression: F1,33 = 11.91, P = .002;
anger: F1,33 = 9.74, P = .004; craving
for marijuana: F1,33 = 18.71, P<.001;
decreased appetite: F1,33 = 18.87, P<.001;
irritability: F1,33 = 7.05, P = .01; and
sleep difficulty: F1,33 = 4.90, P = .03).
Change toward baseline was also observed for restlessness (F1,33
= 3.87, P = .06), which changed, but not significantly,
from baseline 1 to abstinence 1 (P = .06).
Of the 6 items showing significant change from baseline 1 to abstinence
1, 3 replicated in the comparisons of baseline 2 with abstinence 2 (craving
for marijuana: F1,33 = 10.74, P = .002;
decreased appetite: F1,33 = 10.39, P =
.003; and sleep difficulty: F1,33 = 9.76, P
= .004). A significant increase in one new item, strange dreams (F1,33 = 6.95, P = .01), was observed. The d values for these items ranged from 0.61 to 0.80.
A significant difference between baseline 1 and abstinence 1 was observed
on the hostility (F1,33 = 7.06, P = .01, d = 0.63) and interpersonal sensitivity (F1,33
= 4.35, P = .05, d = 0.50)
scales of the Brief Symptom Inventory. Hostility scale scores significantly
decreased back toward baseline during baseline 2 (F1,33 = 8.61, P = .006, d = 0.69), but interpersonal
sensitivity scale scores did not (P = .67). Neither
scale showed significant (P = .55 and .59, respectively)
change from baseline 2 to abstinence 2.
Total craving scores changed significantly from baseline 1 to abstinence
1 (3.4 ± 1.3 vs 4.2 ± 1.5; F1,33 = 9.09, P = .005), from abstinence 1 to baseline 2 (4.2 ± 1.5 vs 2.9
± 1.1; F1,33 = 22.06, P<.001),
and from baseline 2 to abstinence 2 (2.9 ± 1.1 vs 3.8 ± 1.2;
F1,33 = 10.53, P = .003). The d values ranged from 0.7 to 1.0. These patterns were replicated on
both subscales (subscale 1, P<.01 for all 3 comparisons;
and subscale 2, P<.01 for baseline 1 to abstinence
1 and for abstinence 1 to baseline 2 and P = .07
for baseline 2 to abstinence 2).
Of the 5 sleep items, only sleep quality ratings showed significant
change between phases. The sleep quality score decreased significantly from
baseline 1 to abstinence 1 (3.5 ± 1.8 vs 2.4 ± 1.3; F1,33 = 7.14, P = .01, d
= 0.63) and from baseline 2 to abstinence 2 (3.8 ± 1.8 vs 2.9 ±
1.6; F1,33 = 4.02, P = .05, d = 0.47).
Differences between baseline 1 and abstinence 1 scores were observed
on the anger (38.7 ± 2.1 vs 39.9 ± 3.2; F1,24 = 3.55, P = .07), fatigue (40.0 ± 8.0 vs 37.0 ± 3.5;
F1,24 = 8.30, P = .008), and confusion
(40.0 ± 7.2 vs 37.9 ± 5.6; F1,24 = 9.5, P = .005) scales of the Profile of Mood States scales (d range, 0.51-0.84). A significant return toward baseline was observed
on the anger scale score from abstinence 1 to baseline 2 (39.9 ± 3.2
vs 38.0 ± 1.8; F1,24 = 8.49, P
= .008, d = 0.80), but not on the fatigue and confusion
scales scores. No Profile of Mood States depression scales showed significant
change from baseline 2 to abstinence 2.
PHYSIOLOGICAL MEASURES
The mean body weight decreased significantly from baseline 1 to abstinence
1 (F1,33 = 5.77, P = .02, d = 0.57), increased from abstinence 1 to baseline 2 (F1,33
= 5.09, P = .003, d = 0.53),
and decreased from baseline 2 to abstinence 2 (F1,33 = 11.23, P = .002, d = 0.79) (Figure 3). Heart rate and blood pressure
did not differ significantly between the baseline and abstinence phases (P>.05).
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Figure 3. The mean change in body weight
from baseline is presented across study days (N = 12). Significant differences
(P<.05) were observed between phases and between days within
the abstinence phases. MJ indicates marijuana smoking phase; ABS, marijuana
abstinence phase.
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COLLATERAL OBSERVER
Collateral observer ratings of irritability (F1,33 = 6.74, P = .01) and restlessness (F1,33 = 5.16, P = .03) increased significantly from baseline 1 to abstinence
1 and decreased significantly from abstinence 1 to baseline 2 (irritability:
F1,33 = 5.34, P = .03; and restlessness:
F1,33 = 10.01, P = .003), but did not
show significant increases during abstinence 2 (P
= .10 and .12, respectively). Aggression ratings increased, but not significantly,
from baseline 1 to abstinence 2 (F1,33 = 3.54, P = .07), decreased significantly from abstinence 1 to baseline 2 (F1,33 = 4.36, P = .04), and increased significantly
from baseline 2 to abstinence 2 (F1,33 = 5.41, P = .03). The d values ranged from 0.80 to
1.28.
TIME-COURSE EFFECTS
Body weight showed significant change across days within phases (ie,
time-course effects) (F6,66 = 7.58, P
= .001) such that weight appeared to decrease linearly across both abstinence
phases (Figure 3). No significant
differences were observed across days within the abstinence phases for any
of the other dependent variables that changed significantly between phases
(P>.05).
OTHER SUBSTANCE USE
The 3 regular tobacco cigarette smokers used a similar number of cigarettes
during the baseline and abstinence phases. Two occasional cigarette smokers
(<2 days per week) reported smoking during the abstinence phases but not
during the baseline phases. The number of alcoholic and caffeinated drinks
did not differ between the abstinence and baseline phases.
COMMENT
This outpatient study validated specific symptoms of marijuana withdrawal,
and showed they were reliable and clinically significant. These symptoms increased
during marijuana abstinence, returned to baseline when marijuana smoking resumed,
and increased again when abstinence was reinitiated, suggesting that they
were caused by cessation of marijuana use. Collateral observers confirmed
participant reports, providing further support for their validity and significance.
These findings support and extend those from recent studies13, 14 of marijuana abstinence effects conducted
in residential settings. Such consistent reports of emotional and behavioral
symptoms across settings suggest that these types of symptoms are the hallmark
of the acute marijuana abstinence syndrome. The severity of the symptoms appeared
to be greater in the present outpatient study, perhaps because the inpatient
environment diminished the experience of marijuana abstinence effects. For
example, increased aggression was observed in this outpatient study, but not
in the inpatient studies. Aggression may be a more severe form of the irritability
that was observed during the inpatient studies. Hence, the aggression reported
in the outpatient study might be an example of how environmental factors such
as provocation can be crucial to the expression of an abstinence symptom.
Indeed, increased aggression has also been observed during marijuana abstinence
in a laboratory model of provoked aggression.28
The withdrawal symptoms observed in the present study were also consistent
with those reported in clinical and general population studies.15, 29, 30, 31
For example, 67% of marijuana-dependent adolescents in residential care described
a history of marijuana withdrawal symptoms that included irritability, restlessness,
depressed mood, sleep difficulty, and fatigue or yawning.29
A previous study15 of adults seeking treatment
for marijuana dependence showed a similar but more severe pattern of withdrawal
symptoms than that observed in the present study (mean WDS, 14.8 vs 8.2).
This difference may be a consequence of contrasting methods of symptom reporting.
Alternatively, treatment seekers may represent the marijuana users who experience
the most severe withdrawal symptoms. The participants in the present study
reported marijuana use patterns similar to the treatment seekers assessed
in a previous study.15 Of the 4 study participants
who experienced the greatest withdrawal severity, 3 had previously sought
treatment for marijuana dependence. This explanation for the increased withdrawal
severity is consistent with studies32 showing
that tobacco cigarette smokers attending cessation programs report greater
withdrawal severity than self-quitters or those that stop smoking for a study
but are not planning to quit.
The affective symptoms observed during short-term marijuana abstinence
overlap substantially with those observed in other drug withdrawal syndromes.33 Studies34, 35
in laboratory animals indicate that reductions in mesolimbic dopamine transmission
and elevations in extracellular-releasing factor concentrations observed in
the limbic system following withdrawal from cannabinoids closely resemble
the responses seen with other major drugs of abuse. The behavioral consequences
of these neurobiological changes observed during withdrawal are consistent
with the type of negative affective symptoms reported by our participants
and by patients withdrawing from other substances. Such findings have led
to speculation that negative affect may be the common hallmark of withdrawal
across most drugs of abuse.36
The symptoms and severity of marijuana withdrawal appear to most closely
resemble those observed during nicotine withdrawal. We compared the WDSs of
our participants with those reported during nicotine withdrawal in 2 nicotine
withdrawal studies37, 38 similar
to the present study. Both of these studies used an identical 0 to 3 scale
that included all of the items in our WDS plus one additional item (somatic
complaints). For comparison, we used the average change in WDS from baseline
1 to abstinence 1. The WDS increased 181% in the present study, compared with
142% and 226% in the 2 nicotine withdrawal studies.
Marijuana withdrawal, like nicotine withdrawal, appears less severe
than alcohol or opioid withdrawal because it does not produce dramatic physical
symptoms. Nevertheless, the behavioral and emotional withdrawal symptoms associated
with marijuana withdrawal and other drug withdrawal syndromes may be as, if
not more, important than physical symptoms in contributing to the development
of dependence and the undermining of abstinence attempts.
Limitations of the present study include the following. First, the sample
included only daily heavy marijuana smokers who reported withdrawal symptoms
during prior periods of marijuana abstinence. As such, this study does not
address the prevalence of withdrawal, and the findings cannot be generalized
to less severe marijuana users or to those who use medically supervised marijuana.
Whether most marijuana smokers who do not use as frequently as those studied
herein experience clinically significant withdrawal must be determined in
future studies.
Second, the short cessation period prevented an examination of the course
of the marijuana abstinence syndrome. With the exception of body weight, none
of the observed abstinence effects showed evidence of change during the abstinence
periods, which is consistent with prior short-term inpatient studies. A recent
outpatient study18 suggested that some symptoms
of marijuana withdrawal might remain elevated for at least 3 to 4 weeks. Controlled
studies32 of the time course are necessary
to determine whether the abstinence effects observed in the existing studies
reflect true time-limited withdrawal effects or merely represent offset effects
that occur during abstinence and then stabilize.
Third, the ABAB experimental design most likely affected the experience
of marijuana abstinence. Participants knew that abstinence would last only
3 days, and before abstinence phase 2, they had a recent experience with abstinence
(phase 1). Hence, withdrawal severity during phase 2 may have been affected
by the recent experience coping with a short period of abstinence, a change
in expectancies, or a decrease in THC levels.
Fourth, we did not assess neurocognitive effects of abstinence. Prior
studies39 reported that heavy marijuana users
exhibit cognitive impairment following at least one day of abstinence, but
suggested that these effects were more likely due to a residue of drug in
the brain or neurotoxic effects of long-term use rather than withdrawal. Minimal
effects of withdrawal on cognitive and psychomotor performance tasks were
observed in recent inpatient studies.13, 14
Because heavy marijuana use has clearly been associated with cognitive deficits,
more study of neurocognitive functioning during cessation attempts is warranted.
Fifth, we did not statistically control for multiple comparison tests
and, thus, increased the risk of false-positive findings. All significant
findings were consistent with previous research on marijuana withdrawal, and
unexpected significant findings did not emerge, suggesting that the primary
findings were not spurious.
The present study provides new and confirmatory evidence about marijuana
withdrawal. The study defined several valid and reliable symptoms that produce
a significant amount of observable distress in long-term heavy marijuana users.
Like other drug withdrawal syndromes, individual variability exists. Many
questions about marijuana withdrawal remain unanswered. Which and how many
marijuana users experience significant withdrawal is not known. How marijuana
withdrawal affects quit attempts has not been studied. We know that quit rates
during treatment for marijuana dependence are similar to those for other drug
dependencies, indicating that these patients find it difficult to stop.3, 4, 5 If marijuana withdrawal
undermines these cessation attempts, then behavioral or pharmacological treatments
targeting withdrawal may be helpful in the treatment of marijuana dependence.
AUTHOR INFORMATION
Accepted for publication March 23, 2001.
This study was supported by research grants R01-DA12471, T32-DA07242,
and K02-00109 from the National Institute on Drug Abuse, Bethesda, Md.
Presented in part at the College of Problems on Drug Dependence Conference,
San Juan, Puerto Rico, June 19, 2000.
We thank Marilyn Huestis for consultation on the urinalysis testing
procedures.
From the Departments of Psychiatry (Drs Budney, Hughes, and Moore)
and Psychology (Drs Budney and Hughes), The University of Vermont, Burlington;
and the US Air Force, Biomedical Science Corps, Minot, ND (Dr Novy).
Corresponding author and reprints: Alan J. Budney, PhD, Department
of Psychiatry, The University of Vermont, 54 W Twin Oaks Terr, Suite 9, S
Burlington, VT 05403 (e-mail: abudney{at}zoo.uvm.edu).
REFERENCES
| |
1. Substance Abuse and Mental Health Services Administration. Summary of Findings From the 1998 National Household
Survey on Drug Abuse. Rockville, Md: US Dept of Health and Human Services; 1999.
2. Substance Abuse and Mental Health Services Administration. National Admissions to Substance Abuse Treatment
Services: The Treatment Episode Data Set (TEDS), 1992-1996. Rockville, Md: US Dept of Health and Human Services; 1998.
3. Budney AJ, Higgins ST, Radonovich KJ, Novy PL. Adding voucher-based incentives to coping skills and motivational enhancement
improves outcomes during treatment for marijuana dependence. J Consult Clin Psychol. 2000;68:1051-1061.
FULL TEXT
|
ISI
| PUBMED
4. Stephens RS, Roffman RA, Simpson EE. Treating adult marijuana dependence: a test of the relapse prevention
model. J Consult Clin Psychol. 1994;62:92-99.
FULL TEXT
|
ISI
| PUBMED
5. Stephens RS, Roffman RA, Curtin L. Comparison of extended versus brief treatments for marijuana use. J Consult Clin Psychol. 2000;68:898-908.
FULL TEXT
|
ISI
| PUBMED
6. Kaymakcalan S. Tolerance to and dependence on cannabis. Bull Narc. 1973;25:39-47.
7. Beardsley PM, Balster RL, Harris LS. Dependence on tetrahydrocannabinol in rhesus monkeys. J Pharmacol Exp Ther. 1986;239:311-319.
FREE FULL TEXT
8. Aceto M, Scates S, Lowe J, Martin B. Dependence on -9 tetrahydrocannabinol: studies on precipitated
and abrupt withdrawal. J Pharmacol Exp Ther. 1996;278:1290-1295.
FREE FULL TEXT
9. Lichtman AH, Wiley JL, LaVecchia KL, Neviaser ST, Arthur DB, Wilson DM, Martin BR. Effects of SR 141716A after acute or chronic cannabinoid administration
in dogs. Eur J Pharmacol. 1998;357:139-148.
FULL TEXT
|
ISI
| PUBMED
10. Mendelson JH, Mello NK, Lex BW, Bavli S. Marijuana withdrawal syndrome in a woman. Am J Psychiatry. 1984;141:1289-1290.
FREE FULL TEXT
11. Jones RT, Benowitz N. The 30-day trip: clinical studies of cannabis tolerance and dependence. In: Braude MC, Szara S, eds. Pharmacology of Marihuana. New York, NY: Raven Press; 1976:627-642.
12. Cohen S, Lessin PJ, Hahn PM, Tyrell ED. A 94-day cannabis study. In: Braude MC, Szara S, eds. Pharmacology of Marihuana. New York, NY: Raven Press; 1976:621-626.
13. Haney M, Comer SD, Ward AS, Foltin RW, Fischman MW. Abstinence symptoms following oral THC administration to humans. Psychopharmacology (Berl). 1999;141:385-394.
FULL TEXT
| PUBMED
14. Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW. Abstinence symptoms following smoked marijuana in humans. Psychopharmacology (Berl). 1999;141:395-404.
FULL TEXT
| PUBMED
15. Budney AJ, Novy PL, Hughes JR. Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction. 1999;94:1311-1322.
FULL TEXT
|
ISI
| PUBMED
16. Siegel S. Classical conditioning, drug tolerance, and drug dependence. In: Israel Y, Glaser FB, Kalant H, Popham RE, Schmidt W, Smart RG,
eds. Research Advances in Alcohol and Drug Problems.
New York, NY: Plenum Press; 1983:207-246.
17. Wikler A. Opioid Dependence: Mechanisms and Treatment. New York, NY: Plenum Press; 1980.
18. Kouri EM, Pope HG. Abstinence symptoms during withdrawal from chronic marijuana use. Exp Clin Psychopharmacol. 2000;8:483-492.
FULL TEXT
|
ISI
| PUBMED
19. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition. Washington, DC: American Psychiatric Association; 1994.
20. Sobel LC, Sobel MB. Timeline follow-back: a technique for assessing self-reported alcohol
consumption. In: Allen JP, Litten RZ, eds. Measuring Alcohol
Consumption: Psychosocial and Biochemical Methods. Totowa, NJ: Humana
Press; 1992:41-72.
21. Hudziak J, Helzer JE, Wetzel MW, Kessel KB, McGee B, Janca A, Przybeck T. The use of the DSM-III-R Checklist for initial
diagnostic assessments. Compr Psychiatry. 1993;34:375-383.
FULL TEXT
|
ISI
| PUBMED
22. Tiffany ST, Drobes DJ. The development and initial validation of a questionnaire on smoking
urges. Br J Addict. 1991;86:1467-1476.
FULL TEXT
|
ISI
| PUBMED
23. Derogatis LR. Brief Symptom Inventory: Administration, Scoring
and Procedures Manual. Minneapolis, Minn: National Computer Systems Inc; 1993.
24. McNair DM, Lorr M, Droppleman LF. Manual for the Profile of Mood States. San Diego, Calif: Educational and Industrial Testing Service; 1971.
25. Carskadon MA, Dement WC, Mitler MM, Guilleminault MD, Zarcone VD, Spiegel R. Self-reports versus sleep laboratory findings in 122 drug-free subjects
with complaints of chronic insomnia. Am J Psychiatry. 1976;133:1382-1388.
FREE FULL TEXT
26. Huestis MA, Cone EJ. Differentiating new marijuana use from residual drug excretion in occasional
marijuana users. J Anal Toxicol. 1998;22:445-454.
ISI
| PUBMED
27. Cohen J. A power primer. Quant Methods Psychol. 1992;112:155-159.
28. Kouri EM, Pope HG, Lukas SE. Changes in aggressive behavior during withdrawal from long-term marijuana
use. Psychopharmacology (Berl). 1999;143:302-308.
FULL TEXT
| PUBMED
29. Crowley TJ, Macdonald MJ, Whitmore EA, Mikulich SK. Cannabis dependence, withdrawal, and reinforcing effects among adolescents
with conduct symptoms and substance use disorders. Drug Alcohol Depend. 1998;50:27-37.
FULL TEXT
|
ISI
| PUBMED
30. Cottler LB, Schuckit MA, Helzer JE, Crowley T, Woody G, Nathan P, Hughes J. The DSM-IV field trial for substance use disorders:
major results. Drug Alcohol Depend. 1995;38:59-69.
FULL TEXT
|
ISI
| PUBMED
31. Weisbeck GA, Schuckit MA, Kalmijn JA, Tipp JE, Bucholz KK, Smith TL. An evaluation of the history of a marijuana withdrawal syndrome in
a large population. Addiction. 1996;91:1469-1478.
FULL TEXT
|
ISI
| PUBMED
32. Hughes J, Higgins S, Hatsukami D. Effects of abstinence from tobacco: a critical review. In: Kozlowski LT, Annis H, Cappell HD, Glaser F, Goodstadt M, Israel
Y, Kalant H, Sellers EM, Vinglis J, eds. Research Advances
in Alcohol and Drug Problems. New York, NY: Plenum Press; 1990:317-398.
33. Hughes JR, Higgins ST, Bickel WK. Nicotine withdrawal versus other drug withdrawal syndromes: similarities
and dissimilarities. Addiction. 1994;89:1461-1470.
FULL TEXT
|
ISI
| PUBMED
34. deFonseca FR, Carrera MRA, Navarro M, Koob GF, Weiss F. Activation of corticotropin-releasing factor in the limbic system during
cannabinoid withdrawal. Science. 1997;276:2050-2054.
FREE FULL TEXT
35. Diana M, Melis M, Muntoni AL, Gessa GL. Mesolimbic dopaminergic decline after cannabinoid withdrawal. Proc Natl Acad Sci U S A. 1998;95:10269-10273.
FREE FULL TEXT
36. Koob GF, Caine SB, Parsons L, Markou A, Weiss F. Opponent process model and psychostimulant addiction. Pharmacol Biochem Behav. 1997;57:513-521.
FULL TEXT
|
ISI
| PUBMED
37. Hughes JR. Tobacco withdrawal in self-quitters. J Consult Clin Psychol. 1992;60:689-697.
FULL TEXT
|
ISI
| PUBMED
38. Hatsukami DK, Dahlgren L, Zimmerman R, Hughes JR. Symptoms of tobacco withdrawal from total cigarette cessation v |
