This field study (n=111) investigated the potential cognitive effects of ecstasy use, improving on previous studies by excluding the use of alcohol or other recreational drugs. The authors found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic-self-regulation, possibly reflecting increased impulsivity. It was unclear if this was a result of ecstasy use or predisposition in ecstasy users.
Abstract
“Aims: In field studies assessing cognitive function in illicit ecstasy users, there are several frequent confounding factors that might plausibly bias the findings toward an overestimate of ecstasy-induced neurocognitive toxicity. We designed an investigation seeking to minimize these possible sources of bias. Design: We compared illicit ecstasy users and non-users while 1) excluding individuals with significant lifetime exposure to other illicit drugs or alcohol; 2) requiring that all participants be members of the “rave” subculture; and 3) testing all participants with breath, urine, and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables, and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons. Setting: Field study. Participants: Fifty-two illicit ecstasy users and 59 non-users, age 18-45. Measurements: Battery of 15 neuropsychological tests tapping a range of cognitive functions. Findings: We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic-self-regulation, possibly reflecting increased impulsivity. However this finding might have reflected a premorbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug. Conclusions: In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings—including our own—and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users.”
Authors: John H. Halpern, Andrea R. Sherwood, James I. Hudson, Staci Gruber, David Kozin & Harrison G. Pope Jr.
Summary
We compared illicit ecstasy users and non-users while adjusting for age, gender, race/ethnicity, family-of-origin variables, and childhood history of conduct disorder and attention deficit hyperactivity disorder.
Ecstasy is an illicit form of MDMA that has been used by 12 million individuals in the United States alone and millions more worldwide. Studies have shown that ecstasy can be neurotoxic to the 5-HT system and may have negative effects on cognitive performance.
However, because of methodological limitations, such as not screening participants for MDMA, other illicit drugs, and alcohol on the day of testing, and not matching groups for non-ecstasy drug use, studies may overestimate differences between ecstasy users and non-users.
To address these problems, we performed a pilot study in 2004 on 23 ecstasy users and 16 non-users. We found that moderate ecstasy users exhibited virtually no significant differences vs. non-users, but heavy ecstasy users differed significantly from non-users on several measures.
Case finders screened potential participants at raves and other sites frequented by the local all-night dance subculture for lifetime use of ecstasy and other drugs.
We recruited participants aged 18-45 years who reported having used ecstasy at least 17 times or having never used ecstasy at all. We excluded participants who had used cannabis more than 100 times or who had consumed more than 50 drinks in a 4-hour period. We chose to exclude non-ecstasy drug use as much as possible without excessively reducing the participant pool, and did not tell people the reasons for their rejection on telephone screen.
Baseline Evaluation
We evaluated participants on telephone screen and administered instruments similar to those used in our pilot study (15), including demographic questions, a semi-structured interview assessing lifetime episodes of use of alcohol and other drugs, plus a detailed history of episodes, doses, and settings of lifetime ecstasy use.
Neuropsychological Testing Visit
Participants were required to abstain from ecstasy, other illicit drugs, and all-night parties for at least 10 days prior to testing.
All participants were administered breathalyzer tests for alcohol and drugs of abuse, and a urine sample was obtained for a drug test. A hair sample was also obtained for a drug test, and participants whose results were positive were excluded from further analysis.
We administered 15 neuropsychological tests, including the Wechsler Adult Intelligence Scale, Revised (WAIS-R), the Rey-Osterreith Complex Figure Test, the Wisconsin Card Sorting Test, the Raven’s Progressive Matrices, the Stroop Test, the California Verbal Learning Test, Second Edition, and the Beck Depression Inventory.
Statistical Analyses
We divided ecstasy users into moderate and heavy groups and performed 2 analyses, comparing all ecstasy users with non-users and comparing moderate and heavy ecstasy users with non-users after adjusting for age, gender, race/ethnicity, 4 family-of-origin variables, childhood conduct disorder, and childhood ADHD.
We calculated the maximum effect sizes that we could exclude at the 0.05 level of significance, using a test for nonequivalence, and presented the results without correction, but caution readers to consider this issue when interpreting the findings.
Of 1500 potential participants, 250 qualified for the baseline evaluation, of whom 116 completed neuropsychological testing. Of these, 111 were evaluable participants, comprising 52 ecstasy users and 59 non-users.
Ecstasy users were more frequently non-white, had lower levels of parental education, and showed lower vocabulary scores than non-users. We found few significant differences between ecstasy users and non-users on most neuropsychological tests, except for lifetime episodes of ecstasy use and Hamilton Depression Scale scores. Heavy users were significantly slower on the Raven’s Progressive Matrices and WAIS-R Digit-Symbol Subtest than nonusers.
We repeated the analysis using a simplified model adjusting only for age, gender, and race/ethnicity, and with exclusion of 6 individuals who slightly exceeded our criteria for other drug use, and found similar results.
We could exclude a medium effect on many cognitive measures between heavy users and non-users, but not a large effect on all measures.
Discussion
We studied 52 ecstasy users and 59 closely matched nonusers to assess neurocognitive performance. We adjusted for numerous potentially confounding variables. Using a rigorous approach, we found few consistent differences between ecstasy users and non-users on wide-ranging measures of verbal and visuospatial memory, verbal fluency, attention, processing speed, manipulative dexterity, and executive cortical functions. Ecstasy users exhibited lower vocabulary scores than non-users, but these differences were likely due to premorbid ability.
Our study found that heavy ecstasy users exhibited a lower proportion of “brief” items on the RSAT, suggesting poorer strategic self-regulation and hence perhaps greater reflection impulsivity. However, it must be cautioned that these observed associations are complex and inconsistent.
Our findings appear inconsistent with past studies that report lowered cognitive functions in ecstasy users, although they are congruent with recent studies suggesting that cognitive effects of ecstasy use are modest.
Recent longitudinal studies of ecstasy users have produced somewhat inconsistent findings. For example, one study found no differences in cognitive performance between ecstasy users and still-naive individuals at baseline, but different results at follow-up.
Recent reviews have acknowledged that there is inconsistent evidence regarding the association between ecstasy use and lowered cognitive performance, and that confounding effects of premorbid traits and other illicit drug use cannot be excluded.
We found no evidence that ecstasy exposure causes neuropsychological deficits. However, it is possible that ecstasy does cause neurotoxicity, albeit only in individuals with high-level exposure or with possible co-factors predisposing them to ecstasy-induced neurotoxicity.
The neurotoxicity of human ecstasy use remains incompletely resolved. However, our findings indicate that illicit ecstasy use does not generally produce lasting residual neurotoxicity.