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J Psychopharmacol. 2009 January 1; 23(1): 14–22. doi: 10.1177/0269881108089587. | PMCID: PMC2637477 |
Copyright © 2009 British Association for Psychopharmacology Disrupted ‘reflection’ impulsivity in cannabis
users but not current or former ecstasy users L Clark,1,2 JP Roiser,3 TW Robbins,1,2 and BJ Sahakian1,4 1Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK 2Department of Experimental Psychology, University of Cambridge, Cambridge, UK 3Institute of Neurology, Queen Square, London, UK 4Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, UK This is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly
cited. Evidence for serotonin involvement in impulsivity has generated interest in the
measurement of impulsivity in regular ecstasy users, who are thought to display
serotonergic dysfunction. However, current findings are inconsistent. Here, we
used a recently developed Information Sampling Test to measure
‘reflection’ impulsivity in 46 current ecstasy users, 14
subjects who used ecstasy in the past, 15 current cannabis users and 19
drug-naïve controls. Despite elevated scores on the Impulsivity
subscale of the Eysenck Impulsiveness-Venturesomeness-Empathy questionnaire, the
current and previous ecstasy users did not differ significantly from the
drug-naive controls on the Information Sampling Test. In contrast, the cannabis
users sampled significantly less information on the task, and tolerated a lower
level of certainty in their decision-making, in comparison to the drug-naive
controls. The effect in cannabis users extends our earlier observations in
amphetamine- and opiate-dependent individuals ( Clark, et al., 2006, Biological Psychiatry
60: 515–522), and suggests that reduced reflection may
be a common cognitive style across regular users of a variety of substances.
However, the lack of effects in the two ecstasy groups suggests that the
relationship between serotonin function, ecstasy use and impulsivity is more
complex. Key words: addiction, cannabis, decision-making, inhibition, MDMA Impaired inhibitory control in drug addiction is thought to underlie a breakdown of
self-regulation that causes individuals to continue drug administration, despite
growing awareness of the associated negative consequences ( Goldstein and Volkow, 2002; Jentsch and Taylor, 1999; Lyvers,
2000). Inhibitory processes can be quantified with neurocognitive measures of
impulsivity, where deficient performance has been demonstrated in regular users of a
wide range of substances, including stimulants, opiates and alcohol ( Bjork, et al., 2004; Fillmore and Rush, 2002; Forman, et al., 2004). Impulsivity has
received particular attention in relation to the regular use of
3,4-methylenedioxymethamphetamine (MDMA) or ‘ecstasy’. Studies
of experimental animals have shown that MDMA has selective neurotoxic effects on
serotonin (5-hydroxytryptamine, 5-HT) neurons ( Gouzoulis-Mayfrank and Daumann, 2006), and this serotonin neurotoxicity
may cause or exacerbate impulsivity in human users. There is a longstanding
association between reduced serotonin neurotransmission and behavioural impulsivity
( Evenden, 1999b; Soubrié, 1986), derived from behavioural pharmacology
studies in experimental animals ( Tye, et
al., 1977) and data associating serotonin metabolite and
precursor reductions with clinical impulse control disorders ( LeMarquand, et al., 1999; Linnoila, et al., 1983).
Consistent with these data, regular ecstasy users were reported to display impulsive
responding on several laboratory tests, including the Matching Familiar Figures Test
(MFFT) ( Morgan, 1998; Morgan, et al., 2002; Morgan, et al., 2006; Quednow, et al., 2007), the Go/No Go test
( Moeller, et al., 2002b)
and the Stroop test ( Halpern, et
al., 2004), in comparison to drug-naïve and
polydrug-using control groups. However, the link between impulsivity and ecstasy use remains problematic. Several
case–control designs in MDMA users have failed to replicate a basic
deficit on inhibitory measures [Go/No Go ( Fox,
et al., 2002; Gouzoulis-Mayfrank, et al., 2003), Stop Signal Test
( von Geusau, et al.,
2004), Stroop test ( Dafters, 2006)].
Where positive results have been reported, these effects may be limited to subsets
of ecstasy users [heavy users ( Halpern, et
al., 2004; Moeller,
et al., 2002b), males ( von Geusau, et al., 2004)] or have not reached
statistically significance at conventional thresholds ( Quednow, et al., 2007). In addition, the
positive results to date have widely assumed that the impulsivity emerged as a
consequence of ecstasy use via serotonergic neurotoxicity, but have not
satisfactorily excluded the possibility that impulsivity pre-dates drug-taking,
associated with vulnerability mechanisms ( Lyvers,
2006). At a conceptual level, the 5-HT theory of impulsivity may
represent an over-simplification given evidence from experimental animals that
impulsive responses are negatively related to 5-HT levels in subcortical regions,
but positively related to 5-HT efflux in the prefrontal cortex ( Dalley, et al., 2002). These
effects may cancel out following global serotonergic depletion in humans, and we
previously reported no effects of dietary tryptophan depletion on response
inhibition in healthy volunteers ( Clark, et
al., 2005). A further problem lies in the measurement of impulsivity, which is increasingly
viewed as a multi-factorial construct ( Evenden,
1999b; Reynolds, et al.,
2006). Substance abuse may be differentially associated with various
components of impulsivity. Self-report impulsivity on questionnaire measures is
elevated in substance users of various drugs ( Moeller, et al., 2002a; Sher and Trull, 1994). These groups are also impaired on different
laboratory tests of impulsivity, including delay discounting and response inhibition
( Bickel and Marsch, 2001; Bjork, et al., 2004; Fillmore and Rush, 2002). In the delay
discounting paradigm, impulsivity is defined as preference for immediate small
rewards over larger delayed rewards. On tests of response inhibition, impulsivity is
defined as a failure to suppress automatic or dominant responses. It is striking
that whilst drug users display impairments on each of these measures, these
different aspects of impulsivity are typically only weakly correlated with one
another ( Dom, et al., 2007;
Reynolds, et al., 2006). The present report focussed on a further aspect of impulsivity, which has received
less attention in the context of drug use. ‘Reflection’
impulsivity refers to the tendency to gather and evaluate information prior to
decision-making, where impulsivity is associated with a failure of reflective
processing. The construct has typically been measured in children using the MFFT
( Kagan, 1966), where the subject is
presented with a template picture (e.g. a bicycle) and six similar variants. One
variant is identical to the template, and must be identified on each trial.
Impulsivity is indicated by rapid, inaccurate decisions. Two experiments in ecstasy
users by Morgan (1998) reported reduced MFFT
accuracy without significant effects on MFFT latency. However, the MFFT places high
demands on visual search, visual working memory and strategy use, and these domains
may be independently disrupted in recreational ecstasy users ( Fox, et al., 2002), perhaps leading to
inflated error rates (see Block, et
al. (1974) and Clark, et
al. (2006) for further critique of the MFFT). In the present study, we have used an alternative measure of reflection impulsivity
that was designed to circumvent several limitations of the MFFT. In the Information
Sampling Test (IST), the subject is presented with a
5 × 5 matrix that conceals boxes that are each one of two
colours (e.g. red or blue). The subject must decide which of the two colours lies in
the majority under the matrix, by uncovering boxes one at a time. Once uncovered,
boxes remain visible for the remainder of the trial such that the working memory
load is negligible. As well as reducing visual search and working memory demand, the
IST also enables the extraction of a direct measure of information sampling (the
probability of being correct at the point of decision) rather than a speed-accuracy
composite as in the MFFT. Critically, the extent of information sampling on the task
is closely correlated with the number of incorrect judgments, meeting a core
criterion for a test of reflection impulsivity ( Evenden, 1999a). We have also shown previously that information sampling
on the IST was associated with slow, accurate responding on the MFFT, providing
evidence for concurrent validity ( Clark, et
al., 2003). Recently, we reported reduced information
sampling in chronic amphetamine and opiate users ( Clark, et al., 2006). Whilst healthy controls responded
at 81% certainty (95% confidence intervals: 77–85%) when there was no
cost to sampling information, current and former users of amphetamines or opiates
tolerated significantly lower levels of certainty in their decision-making ( Clark, et al., 2006). The
present study aimed to extend these data by examining current and former ecstasy
users, as well as drug-naïve controls, and a fourth group of regular
cannabis users who did not report ecstasy use, as an active control group. We
hypothesized that information sampling would be reduced in the cannabis users, and
that this impulsivity would be further exacerbated in the current and former ecstasy
users as a result of serotonin neurotoxicity. Subjects Participants were 46 current ecstasy users, 14 former ecstasy users, 15 current
cannabis users and 19 drug-naïve controls, who were recruited from
newspaper and magazine advertisements in the Cambridge area. All ecstasy users
reported a minimum of 30 separate uses of the drug. Current users reported
abstinence for at least 3 weeks to allow for short-term recovery of
serotonin function, and the Ex-ecstasy users reported abstinence for at least
1 year. No participant tested positive for recent stimulant use, as
assessed by a blood screen. Demographic characteristics are displayed in Table 1. All participants
completed the National Adult Reading Test (NART) ( Nelson and Willison, 1991) as an estimate of verbal IQ, the
Beck Depression Inventory to record abnormal mood symptoms and the Eysenck
Impulsiveness-Venturesomeness-Empathy (IVE) questionnaire ( Eysenck and Eysenck, 1991) to measure self-reported
impulsivity. The protocol was approved by the Cambridge Local Research Ethics
Committee (LREC number 02/076) and all volunteers provided written informed
consent prior to participation. | Table 1Demographic and personality variables of the four groups |
The information sampling task The task was administered on a touch-sensitive 10.5 inch monitor.
Subjects completed a single practice trial, followed by 10 trials in each of two
conditions: the Fixed Reward (FR) condition and the Reward Conflict (RC)
condition. Condition order was counter-balanced across subjects. On each trial,
subjects were presented with a 5 × 5 matrix of grey
boxes, with two larger coloured panels at the foot of the screen. Touching a
grey box caused the box to open (immediately) to reveal one of the two colours
at the foot of the screen. The subject was asked to decide which colour was in
the majority of the 25 boxes. They were told ‘It is entirely up to
you how many boxes you open before making your decision’ [for
complete instructions, see Clark, et
al. (2006)]. To indicate their decision, the subject touched
the corresponding panel at the foot of the screen, whereupon the remaining boxes
were uncovered and a feedback message ‘Correct! You have won [x]
points’ or ‘Wrong! You have lost 100 points’
was presented immediately, for 2 seconds. In the FR condition, the
subject was awarded 100 points for a correct response, irrespective of the
number of boxes opened. In the RC condition, 250 points were available to win at
the start of the trial, which decreased by 10 points with each box opened,
thereby creating a conflict between the level of certainty and the reward
available. Incorrect responses yielded 100 points deduction in either condition.
In both conditions, the inter-trial interval (ITI) was of variable delay
(minimum 1s) such that the minimum interval between trial onsets was
30 s (e.g. if the trial was completed in 20 s, the ITI was
10 s). This feature was inserted to counteract impulsive behaviour due
to delay aversion. Performance was indexed by the average number of boxes opened, but in addition,
the probability of making a correct choice at the point of decision was
calculated on each trial [ P(Correct); see Clark, et al. (2006) for formula]. Whilst
these two variables are typically correlated with one another, under some
circumstances the number of boxes opened can be a limited index of the
information available; for example, 20 boxes may be distributed 10:10
[ P(Correct) = 0.50] or 15:5
[ P(Correct) = 1.0]. Consequently, the
P(Correct) variable is related more directly to the levels
of certainty tolerated during decision-making, and was therefore the primary
variable for analysis. The number of errors was also recorded to test the impact
of reduced information sampling on decision-making accuracy. Statistical analysis Data were analysed with SPSS (SPSS Inc, Chicago, Illinois, USA) version 14 using
two-tailed parametric tests thresholded at
P < 0.05. Demographic and
questionnaire data were analysed using one-way ANOVA and chi-squared tests as
appropriate. The drug and alcohol use data were analysed with one-way ANOVA
where normality assumptions were met, but in the most part, were not normally
distributed and were analysed with nonparametric tests (Mann–Whitney
and Kruskal–Wallis tests). IST performance was analysed using
mixed-model ANOVA. Significant ANOVA group differences were decomposed using
Tukey’s post hoc tests, or Tamhane’s T2
where variances were unequal. Demographic and drug use characteristics The four groups did not differ significantly in NART-estimated verbal IQ
( F3,90 = 1.49,
P = 0.224), but the gender ratio differed
significantly across groups (χ 2 = 8.81,
P = 0.031) (see Table 1). The ANOVA for group differences in
ageapproached significance
( F3,90 = 2.36,
P = 0.077), due to slightly older age in the
Ex-ecstasy group, although no post hoc tests were significant.
There was a significant group difference in BDI score
( F3,90 = 5.59,
P = 0.001), due to elevated self-reported
depression in the ecstasy and Ex-ecstasy groups in comparison to
drug-naïve controls (Tamhane’s T2,
P < 0.0001 and
P = 0.038 respectively). Neither BDI score
nor age was significantly correlated with IST performance
( r94 = 0.013 and
r94 = 0.177 respectively), so
these variables were not considered as covariates. There was a significant group
difference in self-reported impulsivity on the Eysenck IVE
( F3,90 = 5.03,
P = 0.003) due to elevated scores in the
Current ecstasy and Ex-ecstasy groups in comparison to drug-naïve
controls (Tukey’s, P = 0.007 and
P = 0.006 respectively); the cannabis
group did not differ from drug-naïve controls
( P = 0.469). There were no group differences
on the Venturesomeness
( F3,90 = 0.866,
P = 0.462) or Empathy
( F3,90 = 2.46,
P = 0.067) subscales. Drug and alcohol use data are displayed in Table 2. All subjects consumed alcohol, although
consumption (units/month) differed significantly
( F3,90 = 5.8,
P = 0.001) with the Current ecstasy group
consuming more than that of the drug-naïve controls and cannabis users
(Tamhane’s T2; P < 0.0001
and P = 0.001 respectively). All subjects in
the three drug groups smoked cigarettes, with no differences in monthly
consumption ( F2,72 = 1.7,
P = 0.191). The Current ecstasy and
Ex-ecstasy groups were comparable in terms of lifetime ecstasy exposure
(Mann–Whitney test; Z = 0.52,
P = 0.606) and highest regular dosage
( Z = 1.2,
P = 0.219), but the Current ecstasy group
reported higher peak single dose intake (i.e. the maximum number of tablets
consumed on a single occasion) ( Z = 2.6,
P = 0.009), whereas the Ex-ecstasy group
reported greater maximum frequency of usage per month
( Z = 2.3,
P = 0.019). As expected, the Ex-ecstasy group
also had a longer abstinence period ( Z = 5.6,
P < 0.001). The cannabis users
reported similar current cannabis usage (joints per month) to the two ecstasy
groups (Kruskal–Wallis
χ 2 = 4.5,
P = 0.106), although the two ecstasy groups
reported more total lifetime usage of cannabis
(χ 2 = 6.1,
P = 0.047). Subjects in the two ecstasy
groups were more likely than the cannabis group to have ever used psilocybin
(Fisher’s Exact χ 2 = 19.1,
P < 0.0001), LSD
(χ 2 = 16.2,
P < 0.0001), amphetamine
(χ 2 = 21.2,
P < 0.0001), amyl nitrate
(χ 2 = 21.8,
P < 0.0001), ketamine
(χ 2 = 18.6,
P < 0.0001), cocaine
(χ 2 = 17.9,
P < 0.0001) and opiates
(χ 2 = 12.4,
P = 0.001); although, there was modest usage
of most of these substances in the cannabis group. | Table 2Self-reported drug and alcohol use in the four groups [mean (SD)] |
IST performance A mixed-model ANOVA of P(Correct) data (the probability of being
correct at the point of decision), with Condition (Fixed Reward, Reward
Conflict) as a within-subjects variable and Group and Gender as between-subjects
variables, revealed a significant main effect of Condition
( F1,86 = 95.8,
P < 0.0001). As expected, subjects
tolerated more uncertainty [a lower P(Correct)] in the Reward
Conflict condition than the Fixed Reward condition, thus demonstrating
sensitivity to the task contingencies (see Table 3). There was a significant main effect of Group
( F3,86 = 5.45,
P = 0.002), and a significant
Group × Gender interaction
( F3,86 = 4.53,
P = 0.005). The other terms did not attain
significance (all F < 1), and
notably, the Group × Condition interaction was not
significant ( F3,86 = 0.621,
P = 0.603) suggesting comparable
sensitivity to the change in conditions across groups. Post hoc
group comparisons (Tukey’s) collapsed across Condition showed that
the cannabis users opened significantly fewer boxes compared with the Ex-ecstasy
group ( P = 0.013), and differed at trend from
the Current ecstasy users ( P = 0.076) and the
drug-naïve controls ( P = 0.078).
There were no differences between the ecstasy groups and drug-naïve
controls (see ). An
a priori planned contrast confirmed a significant
difference between the cannabis users and the drug-naive controls
( t32 = 2.31,
P = 0.027) with a large effect size
(Cohen’s
d = 0.81). | Table 3Performance on the Information Sampling Task in the four groups [mean
(SD)] |
A simple main effects analysis of the Group × Gender
interaction assessed the effect of Group in males and females separately,
collapsed across condition. The one-way ANOVA was significant for male subjects
(F3,52 = 6.77,
P = 0.001), where post hoc
comparisons demonstrated significantly reduced information sampling in male
cannabis users compared to each of the other three groups (Tukey’s:
Ex-ecstasy users P < 0.001; Current
ecstasy users P = 0.035; drug-naïve
controls P = 0.038). The one-way ANOVA in
female subjects was not significant
(F3,34 = 1.46,
P = 0.242), but numerically, the female
cannabis group displayed the lowest information sampling of the four groups. A
post hoc analysis compared the extent of cannabis usage
(the main drug of abuse) across male and female subjects in the polydrug group,
and found similar lifetime joints
(t4.1 = 1.05,
P = 0.350) and joints in the last month
(t4.5 = 1.1,
P = 0.324) in the male and female
participants, suggesting that the influence of gender on the IST performance was
not simply due to differences in drug usage. Analysis of the number of boxes opened on the IST revealed a qualitatively
similar pattern of group differences to P(Correct) data, which
is unsurprising given r > 0.9 correlations
between these variables (see task description in Methods). There was a
significant main effect of group in the mixed model ANOVA
(F3,90 = 5.83,
P = 0.001) due to reduced information
sampling in the cannabis users compared with the Ex-ecstasy group
(Tukey’s P = 0.020) and the
Current ecstasy group (P = 0.059). There were
greater group differences in the male subjects
(F3,52 = 7.07,
P < 0.0001) than in the females
(F3,34 = 1.83,
P = 0.161). Errors committed on the IST was
inversely correlated with boxes opened
(r94 = –0.526,
P < 0.0001) and
P(Correct)
(r94 = –0.566,
P < 0.0001), confirming a core
principle of reflection impulsivity. However, the mixed-model ANOVA of
IST-errors found no significant main effect of Group
(F3,90 = 0.258,
P = 0.855) or
Group × Condition interaction
(F3,90 = 1.80,
P = 0.152). Finally, we examined the
correlation between Impulsivity and Venturesomeness scales of the Eysenck IVE,
and IST performance [P(Correct) collapsed across condition].
There was no significant association in the overall group (Impulsivity:
r94 = 0.003,
P = 0.974; Venturesomeness
r94 = 0.043,
P = 0.678) or in any of the four groups
(r = −0.33 to +0.19). The present study used a recently developed IST to measure reflection impulsivity in
current and former ecstasy users, cannabis users and drug-naïve controls.
In the Fixed Reward condition (where there was no penalty for sampling further
information), the drug-naïve control group sampled information to a point
of 85% certainty (95% confidence intervals: 80–89%), similar to healthy
performance in our previous study ( Clark, et
al., 2006). Moreover, the number of boxes opened and the
level of certainty tolerated during decision-making were both inversely correlated
with incorrect judgments in the overall sample
( n = 94). This demonstrates the central feature
of a test of reflection impulsivity: the extent of information sampling is
predictive of eventual decision accuracy ( Evenden,
1999a). Regular cannabis users sampled significantly fewer boxes on the IST and tolerated
more uncertainty in making the correct decision, compared with the other groups.
This difference was statistically significant in a planned comparison against the
drug-naïve control group, and the cannabis users sampled significantly less
information than the Ex-ecstasy group in the more conservative Tukey’s
post hoc group comparisons. The cannabis users altered their
information sampling behaviour to a similar degree between the Fixed Reward and
Reward Decrement conditions, compared with the other groups (i.e. the nonsignificant
Group × Condition interaction term). This indicates
comparable sensitivity to the change in reward contingencies, and suggests that the
reduced information sampling behaviour was not simply attributable to a lack of
motivation in the cannabis group. These data are also consistent with a report of
risky decision-making (on the Iowa Gambling Task) in regular marijuana users ( Whitlow, et al., 2004).
Decision-making impairments on complex tests like the Iowa Gambling Task may
putatively arise from a failure of pre-decisional information sampling or
evaluation. Our findings extend our earlier observation of reduced information
sampling in current and former users of amphetamines or opiates, who met DSM-IV
criteria for dependence ( Clark, et
al., 2006). Given the presence of this effect across multiple
substances of abuse with distinct pharmacological targets (amphetamines, opiates,
cannabis), we suggest that impaired reflection impulsivity may represent a cognitive
style associated with the pre-existing vulnerability to recreational drug use and
later dependence, consistent with data from high-risk prospective studies ( Nigg, et al., 2006; Tarter, et al., 2004). We were unable to detect any significant group differences on the IST between the
ecstasy-using groups and the drug-naïve controls. Several other studies
have failed to substantiate the link between ecstasy use and other aspects of
impulsivity, including the Stroop and Go/No Go tests ( Dafters, 2006; Fox, et
al., 2002; Gouzoulis-Mayfrank,
et al., 2003). However, our findings fail to
replicate several studies that have demonstrated impulsivity in regular ecstasy
users on another widely used test of reflection, the MFFT ( Morgan, 1998; Morgan,
et al., 2002; Morgan, et al., 2006; Quednow, et al., 2007). The ecstasy users in the
present study reported moderate use of other illicit substances, including similar
cannabis usage to the cannabis group. The two ecstasy groups were also more likely
than the cannabis group to have used a range of other substances, including
amphetamine, cocaine and opiates. Consequently, if reduced reflection is a
pre-existing cognitive style associated with general recreational drug use, we would
expect this effect to have also been present in the two ecstasy groups. Lack of
statistical power seems unlikely to explain the negative result, as the ecstasy
groups actually sampled more information (in terms of boxes opened), on average,
than the drug-naïve controls. In addition, the group size of 46 current
ecstasy users is reasonably large for studies of this kind, and the level of ecstasy
consumption was considerable (e.g. lifetime usage means of 609 and 1001 in the
Current and Ex-ecstasy groups respectively), compared with the wider
neuropsychological literature [e.g. 458 tablets in Quednow, et al. (2007)]. There are several possible explanations for the discrepancy with the studies by
Morgan, et al. (1998, 2002, 2006), and Quednow, et al. (2007). One consideration is
the duration of abstinence from ecstasy, which was relatively long in the present
study (> 3 weeks) but much shorter in the positive studies,
ranging from 3 days (mean 17 days; Quednow, et
al., 2007) to 5 days (Morgan, et al., 2005).
Studies in experimental animals reveal recoverable reductions in serotonin function
1–2 weeks after dosing that do not indicate neurotoxicity ( Gouzoulis-Mayfrank & Daumann 2006). In
addition, studies of other drugs indicate that short-term withdrawal may exacerbate
behavioural impulsivity (see below). Lyvers and
Hasking (2004) recommended a 1-month abstinence window for
neuropsychological studies. Hence, the positive MFFT results by Morgan, et
al. and Quednow, et al. could be caused by semi-acute
effects of serotonin depletion upon task performance. We have shown previously that IST performance is related to MFFT performance in
healthy volunteers: fast, inaccurate responders on the MFFT opened significantly
fewer boxes on the IST than slow, accurate responders ( Clark, et al., 2003). However, the MFFT
involves a number of extraneous additional processes, including visual search,
visual working memory and strategy implementation, which may be independently
impaired in regular ecstasy users ( Fox, et
al., 2002; Halpern,
et al., 2004; Wareing, et al., 2005). The design of the IST
explicitly aimed to minimize these extraneous demands. In the MFFT study by Morgan (1998), there was a group difference in
MFFT accuracy but not latency, which may be plausibly explained as a more general
impairment. Other studies, however, reported significant differences in both speed
and accuracy ( Morgan, et al.,
2006; Morgan, et al.,
2002), which is likely to indicate impulsivity. Additional factors may mediate the deficits in laboratory impulsivity in ecstasy
users, and contribute to variability across studies. Gender may be one such
variable: in the present study, the reduced information sampling in the cannabis
group was mainly attributable to the male subjects, and other studies also described
greater neuropsychological impairments in male drug users than in female drug users
( Ersche, et al., 2006;
Stout, et al., 2005),
including ecstasy users ( von Geusau, et
al., 2004). In addition to gender, studies of other groups of
drug-users with the delay discounting paradigm have indicated greater impulsivity in
current users compared with ex-users ( Bickel,
et al., 1999; Petry,
2001). Two distinct mechanisms may contribute to this effect: withdrawal
and/or craving may exacerbate impulsivity in current users ( Field, et al., 2006; Giordano, et al., 2002), but also, less
impulsive drug users may be more capable of achieving successful abstinence ( Bickel, et al., 1999). In the
present data, there was no evidence of the latter effect, as the Current and
Ex-ecstasy users scored similarly on the IVE and IST measures. It is possible that
the periods of abstinence from ecstasy in the Current (>3 weeks) and Ex
(>1 year) ecstasy groups had attenuated impulsivity compared with the
cannabis group, although against this explanation, the ecstasy groups did report
moderate recent usage of other substances, including similar cannabis usage to the
cannabis group in the past month. Whilst we found no evidence of laboratory impulsivity on the IST in the ecstasy
group, self-reported impulsivity on the Eysenck IVE questionnaire was significantly
elevated in the current and former ecstasy users. Questionnaire impulsivity should
indicate trait dispositions that are present prior to the initiation of drug use;
for example, de Win, et al.
(2006) showed no change on the Barratt Impulsiveness Scale before and after
initiation of ecstasy use in a prospective cohort. Previous studies suggest large
variability in trait impulsivity in ecstasy users, with a number of studies
reporting elevations ( Butler and Montgomery,
2004; Morgan, 1998; Parrott, et al., 2000), but
other studies finding no differences ( Travers and
Lyvers, 2005) and one study even finding a significant reduction ( McCann, et al., 1994). In our
data, there was no association between the IVE score and performance on the IST.
These data highlight the multi-factorial nature of impulsivity, and are in keeping
with a number of other reports showing limited associations between state
(laboratory) and trait (questionnaire) measures of impulsivity ( Dom, et al., 2007; Lijffijt, et al., 2004; Reynolds, et al., 2006).
Questionnaire ratings indicate general behavioural tendencies across a variety of
situations, and rely on a subjective perception of one’s behaviour. In
contrast, laboratory tasks provide an objective measure of a specific facet of
impulsivity at a single point in time. Weak correlations between these two sets of
variables may be a realistic expectation. Similarly, our findings do not refute the
possibility that other domains of laboratory impulsivity (e.g. delay discounting,
response inhibition) may be impaired in ecstasy groups. As discussed above, there
are inconsistent findings using tasks of response inhibition in ecstasy users ( Dafters, 2006; Fox, et al., 2002; Gouzoulis-Mayfrank, et al., 2003), and to our
knowledge, no studies have yet explored delay-discounting in regular ecstasy users. Some further limitations of the present study should be noted. Whilst the number of
current ecstasy users was large, the group sizes for the former ecstasy users and
the cannabis users were considerably smaller. In particular, the analyses split by
gender should be treated as preliminary due to the reduced power, and need to be
confirmed in a larger sample. In addition, the two groups of ecstasy users showed a
high degree of polydrug use, although this arguably renders their intact IST
performance even more surprising. In conclusion, these data support the position of reflection impulsivity as a
relevant cognitive dimension in regular drug users, by demonstrating reduced
information sampling in a group of regular cannabis users. Reduced reflection is
likely to have a detrimental impact on wider-scale decision-making capabilities,
with potential relevance for treatment engagement and the ability to maintain
long-term abstinence. Unexpectedly, the present study found no differences in
reflection in current or former ecstasy users, despite evidence of trait impulsivity
in these subjects. These data appear to challenge a simplistic pathway from ecstasy
consumption to elevated impulsivity via serotonin neurotoxicity. This work was funded by a Wellcome Trust programme grant to TWR, BJ Everitt, AC
Roberts and BJS, and a consortium award from the Medical Research Council (UK) and
Wellcome Trust to the Behavioural and Clinical Neurosciences Institute (BCNI). LC is
supported by an Economic and Social Research Council project grant (RES-164-0010).
JPR was supported by a Medical Research Council studentship. This study was
conducted at the Wellcome Trust Clinical Research Facility at
Addenbrooke’s Hospital, Cambridge, and we are grateful to the nurses and
administrative staff for their support. The Information Sampling Task is subject to
international patent PCT/GB2004/003136 and is licensed to Cambridge Cognition plc.
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