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Try out PMC Labs and tell us what you think. Learn More. Although the consequences of MDMA-induced 5-HT neurotoxicity are not fully understood, abstinent MDMA users have been found to have subtle cognitive deficits and altered sleep architecture. The present study sought to test the hypothesis that sleep disturbance plays a role in cognitive deficits in MDMA users. Nineteen abstinent MDMA users and 21 control subjects participated in a 5 d inpatient study in a clinical research unit.
Baseline sleep quality was measured using the Pittsburgh Sleep Quality Inventory. Cognitive performance was tested three times daily using a computerized cognitive battery. On the third day of admission, subjects began a 40 h sleep deprivation period and continued cognitive testing using the same daily schedule.
At baseline, MDMA users performed less accurately than controls on a task of working memory and more impulsively on four of the seven computerized tests. During sleep deprivation, MDMA users, but not controls, became increasingly impulsive, performing more rapidly at the expense of accuracy on tasks of working and short-term memory.
Tests of mediation implicated baseline sleep disturbance in the cognitive decline seen during sleep deprivation. These findings are the first to demonstrate that memory problems in MDMA users may be related, at least in part, to sleep disturbance and suggest that cognitive deficits in MDMA users may become more prominent in situations associated with Can you sleep on extasy deprivation.
Research in animals has shown that MDMA can lead to lasting dose-related and protracted reductions in a variety of brain serotonin 5-HT axonal markers Schmidt, ; Ricaurte et al. Although MDMA-related neurotoxicity is dose related, even single doses of MDMA in the range of those used by humans are associated with ificant lasting reductions in 5-HT axonal markers in animals Schmidt, ; Colado et al. Neuroanatomical studies with immunochemical markers indicate that losses of axonal markers are secondary to a distal axotomy of 5-HT neurons, with sparing of the 5-HT cell body O'Hearn et al.
Humans also appear to be susceptible to MDMA neurotoxicity. Although functional consequences of MDMA-induced brain 5-HT neurotoxicity have not been clearly defined, a large body of data indicates that abstinent MDMA users have cognitive deficits Parrott, ; Kalechstein et al. Working memory and verbal memory are the cognitive domains that have most consistently been found to be impaired in MDMA users, with some data indicating that poor performance on some cognitive tasks may be related to impulsive responding Morgan et al.
Acute and chronic sleep deprivation can lead to cognitive impairment Newhouse et al. Thus, it is possible that cognitive impairments in MDMA users may, in part, be related to sleep disturbance. The purpose of the present research was to test the hypothesis that MDMA users, by virtue of preexistent sleep loss, would be more vulnerable to the negative cognitive effects of sleep deprivation than age- and gender-matched healthy controls.
Recruitment materials did not indicate that the research was specifically directed at the effects of MDMA.
Inclusion in the control group required that subjects had never used MDMA. All subjects needed to express willingness to abstain from illicit substance use for 2 weeks before study participation. Other inclusion criteria included normal Can you sleep on extasy medical screens and physical examinations and negative drug screens with the exception of marijuana, which can remain positive for at least 3 weeks. Exclusion criteria included presence of an Axis I psychiatric diagnosis in which 5-HT has been implicated major depression, bipolar affective disorder, obsessive compulsive disorder, panic disorder, psychosisregular use of prescribed psychotropic medications, more than five lifetime exposures to any amphetamine other than MDMA, or drug or alcohol dependence.
Before enrollment in this research, potential subjects were first screened using an institutional review board-approved scripted phone screen. If subjects met inclusion criteria by phone screen, they were invited for face-to-face screening, at which time they provided informed consent. Before being invited for the face-to-face screening, subjects were instructed to abstain from all illicit drug use for 2 weeks and from any alcohol consumption for at least 3 d.
They were informed that they would be screened for illicit drug use at the time of the screening and that they would not be allowed to participate if drug screens were positive. Face-to-face screening measures included routine blood chemistries, human immunodeficiency virus screening, complete blood counts, and urine testing for drugs of abuse, including cannabinoids, opiates, cocaine metabolites, alcohol, and amphetamines. Subjects who continued to meet all inclusionary criteria were immediately enrolled and admitted to a controlled inpatient clinical research unit for a 5 d period.
If subjects provided inconsistent information, they were excluded from study participation. Cognitive performance was tested by computer three times daily for the first 4 d of admission, and once on the final day of admission, using the Walter Reed Army Institute of Research Performance Assessment Battery WRAIR PABa computerized cognitive test battery that has ly been shown to be sensitive to the effects of sleep deprivation Thorne et al.
As before, tasks included were as follows: the Serial Add and Subtract Test, a machine-paced mental arithmetic task requiring sustained attention; the Logical Reasoning task, a self-paced task of semantic recognition and transformational grammar; the Manikin task, a visuospatial rotation task that tests the ability to mentally manipulate objects and determine the orientation of a specific stimulus; a Code Substitution task, a subject-paced complex attention and incidental learning task similar to the Digit Symbol-Coding test on the Wechsler Intelligence Scale Wechsler, ; a Matching to Sample task, a machine-paced visual discrimination and working memory task; and a Delayed Recall Test, a test of recent memory.
The first three PABs on day 1 were interactive training sessions that were used to ensure that subjects adequately understood each of the seven tasks and were not used in statistical analyses.
After awakening on day 3 of the study, subjects began a 40 h sleep deprivation period, during which time cognitive testing continued using the same daily schedule. During the 40 h sleep deprivation, subjects were closely monitored by the Clinical Research Unit nursing staff to ensure no sleeping. To facilitate wakefulness during the early hours of the second morning between and A.
The seven components for the PSQI include subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction.
Each component is self-rated from 0 to 3. The sum for these seven components yields a global score. Statistical analyses were performed using the SAS System version 9. First-order autocorrelation among residuals was assessed by the Durbin Watson coefficient. A first-order autoregressive covariance matrix [AR 1 ] was used to for Can you sleep on extasy data.
As before McCann et al. Speed per question was quantified as the of responses per minute. The impulsivity factor in high scores when individuals perform quickly and inaccurately, and low scores when they perform slowly and accurately.
The seven components of the PSQI were compared in the two groups using ordinal regression. Mediation was calculated using methods described by Kennyusing multiple linear regressions with a sandwich variance estimator and a Monte Carlo method MacKinnon et al. The global PSQI score was used in the mediation analysis.
In an effort to explore the potential role of cocaine, tobacco, and alcohol use on PAB performance during sleep deprivation, Proc Mixed regressions, with repeated measures adjusting for gender, were used to measure the strength of association between frequency of drug use during the 6 months and accuracy and impulsivity measures that differed ificantly between groups. Frequency of hallucinogen use during the 6 months was insufficiently high to attain strength of association.
A similar of MDMA users and controls reported having used marijuana, alcohol, and tobacco in the past, but a greater proportion of MDMA users had ly used hallucinogens and cocaine Table 1. A small of MDMA users, but no controls, reported exposure to opioids and benzodiazepines Table 1. Ranges are in parentheses. Sleep deprivation Can you sleep on extasy to impaired performance on five of the seven tasks in the WRAIR PAB, as reflected by ificant main effects of Day Table 2 on either accuracy or impulsivity, with only time estimation and a matching-to-sample task remaining unaffected by sleep loss.
Bold indicates ificant or near-ificant differences between groups. Error bars represent SEMs. MDMA users exhibited higher levels of impulsive performance i. MDMA users were also more susceptible to the effects of sleep deprivation on behavioral impulsivity while performing the Code Substitution and Delayed Recall tasks Figs.
As expected, impulsivity and accuracy for these two measures were inversely related, indicating that subjects increased their speed of performance at the expense of accuracy. For all tasks, recovery sleep led to a reversal of the effects of sleep deprivation in both groups Figs. The Monte Carlo method for assessing mediation indicated that preexisting sleep disturbance mediated increased impulsivity of performance on the delayed recall and Logical Reasoning task after sleep deprivation, as well as decreased accuracy on the logical reasoning and Serial Add and Subtract tasks Table 4.
Mediation effects of baseline sleep disturbances on cognitive decline during sleep deprivation in MDMA users. There were no ificant relationships between frequency of hallucinogen or cocaine use on accuracy or impulsivity during sleep deprivation on tasks that differed between groups. The of the present study indicate that abstinent MDMA users are more susceptible to the negative cognitive consequences of 40 h of total sleep deprivation than healthy age- and gender-matched controls on tasks of working and short-term memory.
Notably, for both tasks, deterioration in performance appears to be primarily related to an increase in impulsive responding.
In particular, as the period of sleep deprivation progressed, MDMA users responded more quickly, at the expense of accuracy. Tests of mediation indicated that deterioration in performance on three of seven cognitive tasks during sleep deprivation was mediated by sleep quality, as measured by the PSQI. This observation is consistent with the hypothesis that cognitive deficits in MDMA users are related, in part, to sleep disturbance. The present findings confirm and extend demonstrating poorer cognitive performance in MDMA users see Introduction and provide additional evidence that impulsive responding may underlie poorer performance on some cognitive tests Morgan et al.
In the present study, sleep deprivation in MDMA users, but not controls, was associated with increased behavioral impulsivity. This response to sleep deprivation is atypical because the usual response to sleep deprivation in a healthy adult population is to maintain accuracy at the expense of speed i. It is notable that the two tasks that were differentially affected by sleep deprivation were tasks of working and short-term memory, the cognitive domains most consistently found to be impaired in MDMA users Parrott, ; Kalechstein Can you sleep on extasy al.
Sustained attention is the cognitive domain known to be most immediately and severely impacted by sleep deprivation Banks and Dinges, ; Lim and Dinges,but in the present study, a similar decline in both groups was observed on the Serial Add and Subtract task, a task of sustained attention. Working memory has also been found to be negatively influenced by sleep deprivation Alhola and Polo-Kantola,possibly as a function of an inability to sustain attention on the memory task i. The observation that MDMA users are more sensitive to the effects of sleep deprivation on tasks of working and short-term memory is consistent with the notion that cognitive deficits in MDMA users could be related, in part, to chronic sleep disturbance McCann et al.
A large body of preclinical data, as well as a growing of clinical studies, implicates brain 5-HT systems in cognitive function, including memory processes Schmitt et al. Brain 5-HT systems are also implicated in impulsivity Hollander and Rosen, ; Oquendo and Mann,with decreases in brain 5-HT markers being associated with increased impulsivity. Although MDMA subjects in the current study did not undergo PET imaging as part of this research, their use characteristics are similar to those of subjects ly found to have ificant global reductions of the SERT McCann et al.
Therefore, it is plausible, given the known role of 5-HT in cognitive function and impulsivity, that MDMA-induced 5-HT neurotoxicity is involved in the current observations. Although the present findings suggest that sleep disturbance may play a role in the cognitive deficits seen in MDMA users, they do not clarify the neurobiological basis for these deficits.
In particular, it is possible that MDMA-induced 5-HT neurotoxicity in a disturbance in normal sleep mechanisms and that sleep disturbance le to cognitive dysfunction. It is also possible that MDMA-induced 5-HT neurotoxicity le to direct damage of brain systems involved in cognitive function, or could impact both sleep and cognitive processes.
Conceivably, cognitive deficits, impulsive responding, and sleep alterations could all be unrelated to brain 5-HT neurotoxicity. Future studies using functional imaging methods, possibly in combination with PET measures of 5-HT neuronal integrity, could be useful in clarifying this issue.
In addition, a future study comparing cognitive performance in MDMA users and an age- and gender-matched group of patients with chronic sleep disturbance but no MDMA use would be helpful in determining the role of sleep Can you sleep on extasy per se in the present findings.
Cognitive deficits in MDMA users are subtle and, indeed, only detected using sensitive quantitative testing measures. This fact, plus the fact that cognitive testing scores in MDMA users often overlap with those seen in healthy volunteers, is sometimes used to argue that the deleterious effects of MDMA on cognition are not clinically meaningful.
The present findings suggest an alternate interpretation of the data. In particular, as is common after various forms of neural injury, it is likely that compensatory neuroadaptive processes occur after MDMA-induced 5-HT neurotoxicity.Can you sleep on extasy
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