Sleep apnea in young abstinent recreational
MDMA (“ecstasy”) consumers
Una D. McCann, MD
Francis P. Sgambati, BSE
Alan R. Schwartz, MD
George A. Ricaurte, MD,
Background: Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a popular recreational drug
have defied ready characterization. Obstructive sleep apnea (OSA) is a common form of sleep-
disordered breathing in which brain serotonin dysfunction may play a role. The present study sought
to determine whether abstinent recreational MDMA users have an increased prevalence of OSA.
Methods: We studied 71 medically healthy recreational MDMA users and 62 control subjects
using all-night sleep polysomnography in a controlled inpatient research setting. Rates of apneas,
hypopneas, and apnea hypopnea indices were compared in the 2 groups, controlling for body
mass index, age, race, and gender.
Results: Recreational MDMA users who had been drug free for at least 2 weeks had significantly
increased rates of obstructive sleep apnea and hypopnea compared with controls. The odds ratio
(95% confidence interval) for sleep apnea (mild, moderate, and severe combined) in MDMA users
during non-REM sleep was 8.5 (2.4–30.4), which was greater than that associated with obesity
[6.9 (1.7–28.2)]. Severity of OSA was significantly related to lifetime MDMA exposure.
Conclusions: These findings suggest that prior recreational methylenedioxymethamphetamine
use increases the risk for obstructive sleep apnea and lend support to the notion that brain sero-
tonin neuronal dysfunction plays a role in the pathophysiology of sleep apnea. Neurology®2009;
AHI ? apnea hypopnea index; BMI ? body mass index; DSM-IV ? Diagnostic and Statistical Manual of Mental Disorders, 4th
edition; MDMA ? methylenedioxymethamphetamine; NREM ? non-REM; OR ? odds ratio; OSA ? obstructive sleep apnea;
PSG ? polysomnography; SCID-I ? Scheduled Diagnostic Interview for DSM-IV; SDB ? sleep-disordered breathing.
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is estimated to afflict
approximately 15 million adult Americans1and is characterized by repeated episodes of apnea
or hypopnea during sleep. The pathophysiology of sleep apnea is incompletely understood.
However, the consequences of OSA can be serious and include daytime sleepiness, cognitive
dysfunction, metabolic syndrome, and cardiovascular disease.2Recently, OSA has also been
identified as an independent risk factor for death related to cardiovascular causes.3,4
The neurobiologic underpinnings of OSA are not fully understood. However, there has
been increased interest in the role of central serotonin systems in its pathogenesis. Brain seroto-
nin neurons modulate sleep and breathing patterns through a variety of different mechanisms.
For example, serotonin neurons influence circadian changes in sleep propensity,5mediate
cortical arousal,6act as carbon dioxide chemoreceptors that modulate respiratory drive,7and
innervate muscles that maintain pharyngeal patency.8-11In addition, there is serotonin neuro-
nal input to the respiratory rhythm generator in the brainstem pre-Bo ¨tzinger complex, as well
as to spinal respiratory motor neurons.12,13Therefore, although the pathophysiology of sleep
e-Pub ahead of print on December 2, 2009, at www.neurology.org.
From the Department of Psychiatry (U.D.M., F.P.S.), Department of Medicine, Division of Pulmonary and Critical Care (A.R.S.), and Department
of Neurology (G.A.R.), The Johns Hopkins School of Medicine, Baltimore, MD.
Supported by Public Health Service grants DA16563 (McCann), DA05938 and DA01796401 (Ricaurte), and NCRR grant M01RR002719 (Ford).
Disclosure: Author disclosures are provided at the end of the article.
Editorial, page 1947
Address correspondence and
reprint requests to Dr. Una D.
McCann, Department of
Psychiatry, The Johns Hopkins
School of Medicine, 5501
Hopkins Bayview Circle, Room
5B71c, Baltimore, MD 21224
Copyright © 2009 by AAN Enterprises, Inc.
apnea is complex and may involve a variety of
mechanisms,14there is reason to believe that
altered brain serotonin neuronal function
may be involved.
“ecstasy”) is a popular recreational drug of
abuse and a potent selective brain serotonin
neurotoxin.15,16Studies in animals, including
nonhuman primates, have demonstrated that
MDMA leads to lasting dose-related and pro-
tracted reductions in a variety of brain seroto-
nin axonal markers, and neuroanatomical
studies with immunochemical markers sug-
gest that losses of axonal markers are secondary
to a distal axotomy of serotonin neurons.17,18
PET imaging studies using radioligands that
bind to serotonin transporters provide evidence
that MDMA is also neurotoxic in humans.19-21
Although functional consequences of MDMA-
induced brain serotonin neurotoxicity are not
well understood, available data suggest that ab-
stinent MDMA users have alterations in sleep
architecture22and cognitive function.23-26
The present study was conducted in absti-
nent, otherwise healthy MDMA users whose
use characteristics have previously been
shown to lead to persistent losses of brain se-
rotonin transporters suggestive of serotonin
neurotoxicity. In particular, MDMA users
with similar use patterns in studies with iden-
tical inclusion criteria have previously been
found to have a reduction in brain serotonin
transporters as measured by PET.19The pur-
pose of this study was to determine whether
abstinent MDMA users showed evidence of
sleep-disordered breathing (SDB).
METHODS Subjects. All participants (n ? 71 MDMA us-
ers; n ? 62 controls) were medically healthy individuals who
responded to recruitment materials posted in newspapers and
fliers looking for “club drug users.” The same recruitment mate-
rials were used for both MDMA users and controls, and poten-
tial subjects were not aware that we were specifically interested in
the effects of MDMA. Inclusion in the MDMA subject group
required a self-report of 25 or more separate lifetime uses of
MDMA because such subjects have previously been shown to
have lasting reductions in brain serotonin axonal markers.19,27
Inclusion in the control group required that subjects had never
used MDMA. Inclusion criteria for all subjects included willing-
ness to abstain from illicit substance use for 2 weeks before study
participation, normal results on all medical screening measures
(see below), and negative drug screens (with the exception of
marijuana, which can remain positive for at least 3 weeks). Ex-
clusion criteria included regular use of prescribed psychotropic
medications, previous diagnosis of a sleep disorder, major medi-
cal illness, drug or alcohol dependence, history of significant
head injury, and presence of an Axis I psychiatric diagnosis in
which serotonin has been implicated (major depression, bipolar
affective disorder, obsessive compulsive disorder, panic disorder,
To determine whether interested individuals would be in-
cluded in the study, potential subjects first underwent an initial
institutional review board–approved scripted phone screen.
Questions in the script were designed to determine whether sub-
jects met inclusion and exclusion criteria. All subjects who met
study criteria in the phone screen (for either the MDMA or the
control group) were then invited for face-to-face screening. At
the time of the face-to-face screen, subjects provided informed
written consent before undergoing further evaluation. In addi-
tion to drug testing, additional screening measures included rou-
tine blood chemistries, HIV screening, complete blood counts,
and urine testing for drugs of abuse, including cannabinoids,
opiates, cocaine metabolites, alcohol, and amphetamines. If, af-
ter laboratory and medical examination, individuals continued
to meet full inclusion criteria, they were immediately enrolled
and admitted. Notably, before coming for face-to-face screening,
subjects had been informed that they needed to abstain from all
illicit drug use for 2 weeks, from any alcohol consumption for at
least 3 days, that they would be screened for illicit drug use at the
time of the screening, and that would be excluded from partici-
pation if drug or alcohol screens were positive. All subjects were
also interviewed using the Scheduled Diagnostic Interview for
DSM-IV (SCID-I).28MDMA (and other drug) use was assessed
during the initial phone screen and by a standardized drug ques-
tionnaire, nursing assessment upon admission to the inpatient
Clinical Research Unit, the SCID-I, and an MDMA-specific
questionnaire. If subjects provided inconsistent information,
they were excluded from study participation.
Standard protocol approvals, registrations, and patient
consents. The research described in this article was approved
by an institutional investigational review board. All subjects pro-
vided informed, written consent to participate in the research.
Polysomnography. The research took place in a federally
funded inpatient clinical research unit. While on the clinical re-
search unit, the sleep schedule was regulated, with a “lights-out”
time of 11:00 PM and a “lights-on” time of 7:00 AM. Participants
were not permitted to sleep before lights-out time or sleep past
lights-on time. The overnight polysomnography (PSG) con-
sisted of continuous recordings of right and left electrooculo-
graphic leads, 4 electroencephalographic leads (C3–A3, C4–A1,
O1–A2, O2–A1), submental electromyogram, and bilateral an-
terior tibialis. The electrooculograms and EEGs were recorded at
a minimum of 100 Hz and up to 500 Hz, and EMGs were
recorded at 200 Hz. Respiration of the participant was moni-
tored by a nasal pressure cannula at the nostrils, a thermistor/
thermocouple at the nose and mouth, and thoracic and
abdominal strain gauges. Continuous recording of the partici-
pant’s oxyhemoglobin saturation was obtained by an oximeter.
Scoring of the overnight PSG was visually scored by certified
polysomnographers from the Johns Hopkins Sleep Disorders
Center, following American Academy of Sleep Medicine Guide-
lines.29Apnea and hypopnea measures were characterized as ob-
structive, central, or mixed. Polysomnographers who scored
sleep records were blind to subjects’ group designation (i.e.,
MDMA vs control). The apnea hypopnea index (AHI) was de-
fined as the mean number of apneas plus hypopneas per hour of
sleep, the apnea index was defined as the mean number of apneas
Neurology 73December 8, 2009
per hour, and the hypopnea index was defined as the mean num-
ber of hypopneas per hour. Severity of OSA was defined using
conventional definitions (AHI ?5 ? normal; AHI 5–14 ? mild
OSA; AHI 15–29 ? moderate OSA; AHI ?30 ? severe OSA).
Statistical analysis. Between-group comparisons were per-
formed using a multiple linear regression model comparing dis-
ordered breathing rates in MDMA users and control subjects.
Stepwise variable selection was used to identify potential signifi-
cant covariates, including known risk factors for SDB: body
mass index (BMI), sex, race, and age. In addition, given the
larger number of males in the MDMA group and known gender
differences in the prevalence of SDB, we also conducted an anal-
ysis comparing SDB measures in males only (see supplemental
data on the Neurology®Web site at www.neurology.org). The
significance level used for determining the entry and removal of
the covariates from the model was a p value ?0.15. The variable
remained in the model only if it retained a p value ?0.10. A
multiple logistic regression model was also used to determine the
odds ratio (OR) for mild, moderate, and severe obstructive sleep
apnea (combined) in MDMA users. Binary variables were cre-
ated using the AHI during total sleep, during non-REM
(NREM) sleep, and during REM sleep. The latent variable was
defined as 1 if the AHI was greater than 5 events per hour and 0
otherwise. For the purpose of the logistic regression, age was
studied as a continuous variable, whereas BMI was categorized
into underweight (BMI ?18.5), normal (18.5 ? BMI ? 25),
overweight, (25 ? BMI ? 30), and obese (30 ? BMI ? 40).
To assess the potential association between the total number
of lifetime MDMA exposures and disordered breathing measures
in the MDMA population, Pearson partial correlation coeffi-
cients were determined. In these analyses, an individual MDMA
exposure was defined as MDMA use in a single setting (e.g., a
dance party) and sometimes involved multiple doses over several
hours. The same stepwise selection process as described above
was used to identify covariates. A similar procedure was con-
ducted to explore the potential relationship between prior co-
caine use and SDB, because cocaine has the potential to
produce microvascular brain injury that could potentially in-
fluence our findings. Statistics were conducted using
MATLAB (The Mathworks, Inc., Natick, MA) and SAS (SAS
Institute Inc., Cary, NC).
RESULTS Demographics and recreational drug use
characteristics of subjects are provided in table 1. The
2 groups did not significantly differ with regard to
age or BMI. The proportion of male subjects was
higher in the MDMA group, and the proportion of
African Americans was higher in the control group.
MDMA users, as a group, used more recreational
drugs in the past than control subjects.
MDMA users had greater numbers and rates of
apneas and hypopneas when compared with controls
(table 2 and figure 1), with 80% of the apneas in
MDMA users identified as being of the obstructive
type, 14% being of the mixed type, and the remain-
ing 6% being of the central type. When data were
analyzed using conventional definitions of OSA se-
verity, rates of mild OSA (AHI 5–14) were similar in
the 2 groups, but moderate (AHI 15–29) and severe
(AHI ?30) OSA were only observed in the MDMA
group (figure 1). Of the 24 MDMA subjects who
met criteria for OSA, 22 were aged 31 years or
younger. A Fisher exact test (1-tailed) revealed that
differences in the rate of moderate and severe sleep
apnea observed in the 2 groups were not secondary to
chance (p ? 0.001; table e-1).
Logistic regression during REM, NREM, and to-
tal sleep revealed that MDMA users were at increased
risk for meeting criteria for sleep apnea (mild, mod-
erate, and severe combined), particularly during
Table 1Demographics of MDMA and control
MDMA (n ? 71) Control (n ? 62)
23.2 (18–44) 24.1 (18–46)
24.9 (17.5–39.1)26.5 (18.9–29.3)
192 (30–2,000) NA
69 (97) 38 (61)
Past 6 mo
53 (75)22 (35)
57 (80)6 (10)
Past 6 mo
21 (30)1 (2)
42 (59) 4 (6)
Past 6 mo
24 (34)2 (3)
30 (42)3 (3)
Past 6 mo
11 (15) 1 (2)
Past 6 mo
41 (58) 19 (31)
*Categorical values are expressed as whole numbers. Other
variables are expressed as mean (range).
†Values represent absolute number (%) of subjects in each
group who have ever used a substance in their lifetime and
number of subjects who have used the substance within the
past 6 months.
‡Numbers represent absolute number of individuals in each
§p ? 0.02;¶p ? 0.01;?p ? 0.005. Comparisons were made
using a Fisher exact test.
MDMA ? methylenedioxymethamphetamine; BMI ? body
mass index; NA ? not applicable.
Neurology 73 December 8, 2009
NREM sleep (table 3). During NREM sleep,
MDMA users had more than 8 times the odds of
apnea and hypopnea episodes than controls. When
only male subjects were considered, the OR for SDB
during NREM sleep increased to 11 (table e-2). Prior
MDMA use increased the odds for sleep apnea dur-
ing NREM sleep to a greater degree than BMI in this
Greater lifetime MDMA use was associated with
increased rates of sleep apnea (r ? 0.44, p ? 0.001;
figure 2). Partial correlations between lifetime
MDMA use and sleep apnea and hypopnea indices
(controlling for age, gender, BMI, and race) demon-
strated a significant relationship between these mea-
sures and prior MDMA exposure (table e-3). Prior
use of cocaine was not found to be associated with
DISCUSSION The present study indicates that
prior use of the recreational drug and brain serotonin
neurotoxin, MDMA, is a risk factor for sleep apnea
in otherwise healthy young adults, independent of
age, male gender, race, and obesity. Further, the rela-
tionship between MDMA use and sleep apnea seems
to be directly related to extent of prior MDMA expo-
sure, with greater lifetime MDMA use associated
with increased rates of sleep apnea. These findings
lend support to the view that brain serotonin systems
play a role in the pathophysiology of OSA8,10-13and
suggest that sleep apnea is a potential functional con-
sequence of recreational MDMA use.
Although the present findings further implicate
brain serotonin dysfunction in sleep apnea and hy-
popnea, the precise mechanisms involved are not
clear. Increased rates of apnea and hypopnea in absti-
nent recreational MDMA consumers could be related
to loss of airway patency due to altered serotonergic in-
put to the hypoglossal motor nucleus.8-11Alternatively,
faulty chemoreception by serotonergic neurons,7dis-
ruption of the respiratory rhythm generator,12or
defective serotonergic modulation of respiratory mo-
toneurons.13Preclinical models of MDMA-induced se-
rotonin neurotoxicity may also be useful in clarifying
these important issues.
Functional consequences of MDMA-induced
neurotoxicity in human recreational users have been
difficult to identify. The most consistent behavioral
differences that have been reported in abstinent
MDMA users have been subtle cognitive deficits,23-26
behavioral impulsivity,30,31altered sleep architec-
ture,30and altered neuroendocrine function.32,33The
present study provides evidence that MDMA expo-
sure increases the risk for obstructive sleep apnea,
with rates of sleep apnea and hypopnea being directly
related to prior MDMA exposure. As discussed be-
low, there may be a relationship among OSA and
cognitive deficits and impulsivity in abstinent
MDMA users, but it remains to be clarified.
Apneas and hypopneas, by disrupting sleep, may
contribute to cognitive deficits found in MDMA
users.22-26This possibility is raised by the fact that
chronic sleep disruption is known to have a deleteri-
ous effect on daytime cognitive functioning.34Thus,
arousals during sleep secondary to nocturnal hypop-
neas and apneas could play a role in subtle changes in
Figure 1Apnea hypopnea indices in abstinent MDMA users and controls
Blue diamonds represent apnea hypopnea index values for subjects in methyl-
enedioxymethamphetamine (MDMA) and control groups. OSA ? obstructive sleep apnea.
Table 2 Disordered breathing measures in MDMA users and controls
measureMDMA (n ? 71)Control (n ? 62)p Value
Total apneas and
38.25 (46.28)22.39 (16.83)0.003
NREM apneas and
25.96 (36.36) 13.23 (12.35)0.004
REM apneas and
12.96 (15.00)9.16 (8.33) 0.06
5.57 (6.98) 3.18 (2.34)0.003
4.86 (6.86)2.36 (2.08) 0.003
7.72 (9.71) 6.47 (6.43) 0.13
1.52 (2.77)0.56 (0.61) 0.02
1.32 (3.02)0.42 (0.54) 0.04
2.00 (3.44) 1.14 (1.94)0.02
4.11 (5.35)2.61 (2.08) 0.01
3.59 (5.15)1.94 (1.85) 0.01
5.80 (7.93)5.33 (5.77) 0.33
Values are mean (SD). p Values are derived from a stepwise linear regression procedure
described under Methods.
MDMA ? methylenedioxymethamphetamine; NREM ? non-REM; AHI ? apnea hypopnea
index; AI ? apnea index; HI ? hypopnea index.
Neurology 73 December 8, 2009
cognitive function that have been reported in absti-
nent MDMA users. However, none of the previous
polysomnographic studies in MDMA users30have
found significant decreases in sleep latency in
MDMA users, suggesting that excessive daytime
sleepiness is not the way in which SDB leads to cog-
nitive deficits in abstinent MDMA users. Notably,
another aspect of cognitive function that has been
found to be altered in MDMA users is impulse con-
trol.30,31There is a substantial body of literature indi-
cating that sleep loss in adolescents increases
impulsive and risk-taking behavior.35,36Although in-
triguing, it remains to be determined whether sleep
loss is responsible for behavioral findings in MDMA
users and, further, whether serotonin neurotoxicity
underlies sleep abnormalities and impulsive tenden-
cies in the same individuals.
Limitations of the present study should be ac-
knowledged and include the fact that MDMA users,
as a rule, experiment with multiple substances, most
commonly marijuana. In theory, one or several of
these other substances could play a role in the in-
creased incidence of sleep apneas and hypopneas
found in the present group of MDMA users. How-
ever, although many drug classes have the potential
to influence breathing and respiratory patterns
acutely, there are no data suggesting that any of the
recreational drugs used by these subjects has long-
lasting effects on respiratory function or serotonin
neurons. Although some subjects did test positive for
marijuana, marijuana use has not been identified as a
risk factor for sleep apnea, and exclusion of these sub-
jects did not influence the study outcome. Indeed,
cannabinoids have been proposed as a potential treat-
ment for obstructive sleep apnea.37Cocaine, which has
not associated with SDB in the present study. Another
limitation of this study is that drug use reports were
retrospective, and self-reported prior drug use is subject
of brain serotonin transporters, as measured by PET, to
be significantly associated with self-reported lifetime
MDMA exposure.19Finally, concerns regarding the
role of other drugs of abuse in the present findings are
mitigated by the relationship between extent of prior
current study, the known dose-related neurotoxic ef-
fects of MDMA toward brain serotonin neurons,15-18
and the fact that serotonin has been previously impli-
cated in OSA.8
Additional research will be necessary to determine
whether sleep abnormalities in MDMA users play a
role in subtle cognitive deficits and impulsivity that
have previously been identified in this population.
Studies that evaluate the relationship between brain
serotonin markers and measures of SDB will
strengthen conclusions regarding the role of seroto-
nin neurotoxicity in sleep apnea in MDMA users.
Preclinical and clinical studies coupling respiratory
physiology methodology with functional neuroimag-
ing approaches may be required to determine the
neurobiological basis for our findings.
Statistical analyses were performed by Francis P. Sgambati, BSE, and re-
viewed by Nae-Yuh Wang, PhD (Interdisciplinary Center for Transla-
tional Research Biostatistician).
The authors thank Dr. Nae-Yuh Wang for his biostatistical review of this
manuscript; Emily Dotter, Kristen Kelley, Michael Wilson, and Michael
Palermo for research assistance; and the CRU/ICTR nursing staff for their
participation in the execution of these studies.
Figure 2Apnea hypopnea index vs total lifetime MDMA use
AHI ? apnea hypopnea index; MDMA ? methylenedioxymethamphetamine.
Table 3Multiple logistic regression model identifying risk factors for
NREM and REMNREM onlyREM only
OR (95% CI)p Value OR (95% CI)p Value OR (95% CI)p Value
3.7 (1.4–10.1)0.018.5 (2.4–30.4)0.001 0.9 (0.4–2.0)0.82
0.5 (0.1–5.3) 0.600.7 (0.1–6.8) 0.74 0.7 (0.1–4.1)0.67
25 < BMI
2.0 (0.7–5.8) 0.212.1 (0.6–7.0) 0.240.6 (0.2–1.5) 0.26
?0.00016.9 (1.7–28.2)0.01 3.2 (1.2–8.7)0.03
3.3 (1.2–9.7) 0.03 3.2 (0.9–10.8)0.061.9 (0.8–4.4) 0.13
1.1 (1.0–1.2) 0.101.2 (1.0–1.3) 0.01 1.1 (1.0–1.2)0.01
Neurology 73December 8, 2009
Dr. McCann has served on a scientific advisory board and speakers’ bu-
reau for Jazz Pharmaceuticals; has received honoraria from the Public
Health Service and the Veterans Administration (grant reviews); and re-
ceives research support from the NIH [NIDA R01 DA010217 (PI),
NIDA R01 DA16563 (PI), NIDA 1R01 DA017231-01 A1 (Coinvestiga-
tor), NIDA 2 R01 DA05707 (Coinvestigator), NIDA 2 R01 DA05938
(Coinvestigator), and NICHHD 1 R01 HD050202-01 (Coinvestiga-
tor)]. Mr. Sgambati reports no disclosures. Dr. Schwartz may accrue reve-
nue on US Patent 6457472 (Issued: October 1, 2002): Transtracheal
insufflation for treatment of obstructive sleep apnea; serves as a scientific
advisor to Apnex, Scientific Advisor, and Cardiac Concepts; and receives
research support from the NIH [HL50381 (PI), SCCOR program (Coin-
vestigator), HL37379 (Coinvestigator), and NCRR (Sleep Core Director,
ICTR and Clinical Research Unit)]. Dr. Ricaurte receives research sup-
port from the NIH [NIDA K05 DA01796401 (PI), NIDA 5 R01
DA05938 (PI), and NICHHD 1 R01 HD050202-01 (PI)].
Received March 12, 2009. Accepted in final form August 12, 2009.
1.Somers VK, White DP, Amin R, et al. Sleep apnea and car-
College of Cardiology Foundation Scientific Statement from
the American Heart Association Council for High Blood
Pressure Research Professional Education Committee, Coun-
cil on Clinical Cardiology, Stroke Council, and Council on
Cardiovascular Nursing in collaboration with the National
Heart, Lung, and Blood Institute National Center on Sleep
Disorders Research (National Institutes of Health). Circula-
2. Pack AI. Advances in sleep-disordered breathing. Am J Re-
spir Crit Care Med 2006;173:7–15.
3.Young T, Finn L, Peppard PE, et al. Sleep disordered
breathing and mortality: eighteen-year follow-up of the
Wisconsin sleep cohort. Sleep 2008;31:1071–1078.
4. Marshall NS, Wong KK, Liu PY, Cullen SR, Knuiman
MW, Grunstein RR. Sleep apnea as an independent risk
factor for all-cause mortality: the Busselton Health Study.
5.Challet E. Minireview: entrainment of the suprachiasmatic
clockwork in diurnal and nocturnal mammals. Endocri-
6. Saper CB, Scammell TE, Lu J. Hypothalamic regulation of
sleep and circadian rhythms. Nature 2005;437:1257–1263.
7. Richerson GB. Serotonergic neurons as carbon dioxide
sensors that maintain pH homeostasis. Nat Rev Neurosci
8.Veasey SC. Serotonin agonists and antagonists in obstruc-
tive sleep apnea: therapeutic potential. Am J Respir Med
9. Volgin DV, Fay R, Kubin L. Postnatal development of
serotonin 1B, 2 A and 2C receptors in brainstem motoneu-
rons. Eur J Neurosci 2003;17:1179–1188.
10.Horner RL. Control of genioglossus muscle by sleep state-
dependent neuromodulators. Adv Exp Med Biol 2008;
11. Horner RL. Neuromodulation of hypoglossal motoneurons
during sleep. Respir Physiol Neurobiol 2008;164:179–196.
12.Tryba AK, Pen ˜a F, Ramirez JM. Gasping activity in vitro:
a rhythm dependent on 5-HT2A receptors. J Neurosci
13.Mahamed S, Mitchell GS. Simulated apnoeas induce
serotonin-dependent respiratory long-term facilitation in
rats. J Physiol 2008;586:2171–2181.
14.Eckert DJ, Malhotra A, Jordan AS. Mechanisms of apnea.
Prog Cardiovasc Dis 2009;51:313–323.
Green AR, Mechan AO, Elliott JM, O’Shea E, Colado
MI. The pharmacology and clinical pharmacology of 3,4-
methylenedioxymethamphetamine (MDMA, “ecstasy”).
Pharmacol Rev 2003;55:463–508.
Gudelsky GA, Yamamoto BK. Actions of 3,4-meth-
ylenedioxymethamphetamine (MDMA) on cerebral
dopaminergic, serotonergic and cholinergic neurons. Phar-
macol Biochem Behav 2008;90:198–207.
O’Hearn E, Battaglia G, De Souza EB, Kuhar MJ, Mol-
liver ME. Methylenedioxyamphetamine (MDA) and
methylenedioxymethamphetamine (MDMA) cause selec-
tive ablation of serotonergic axon terminals in forebrain:
immunocytochemical evidence for neurotoxicity. J Neuro-
Hatzidimitriou G, McCann UD, Ricaurte GA. Altered se-
rotonin innervation patterns in the forebrain of monkeys
treated with (?/?)3,4-methylenedioxymethamphetamine
seven years previously: factors influencing abnormal recov-
ery. J Neurosci 1999;19:5096–5107.
McCann UD, Szabo Z, Seckin E, et al. Quantitative PET
studies of the serotonin transporter in MDMA users and
controls using [11C]McN5652 and [11C]DASB. Neuro-
Semple DM, Ebmeier KP, Glabus MF, O’Carroll RE,
Johnstone EC. Reduced in vivo binding to the serotonin
transporter in the cerebral cortex of MDMA (“ecstasy”)
users. Br J Psychiatry 1999;176:63–69.
Thomasius R, Zapletalova P, Petersen K, et al. Mood, cog-
nition and serotonin transporter availability in current and
former ecstasy (MDMA) users: the longitudinal perspec-
tive. J Psychopharmacol 2006;20:211–225.
McCann UD, Ricaurte GA. Effects of (?/?) 3,4-
methylenedioxymethamphetamine (MDMA) on sleep and
circadian rhythms. Sci World J 2007;7:231–238.
Parrott AC. Human research on MDMA (3,4-methylene-
dioxymethamphetamine) neurotoxicity: cognitive and be-
havioural indices of change. Neuropsychobiology 2000;
Zakzanis KK, Campbell Z, Jovanovski D. The neuropsy-
chology of ecstasy (MDMA) use: a quantitative review.
Hum Psychopharmacol 2007;22:427–435.
Kalechstein AD, De La Garza R II, Mahoney JJ III, Fante-
grossi WE, Newton TF. MDMA use and neurocognition:
a meta-analytic review. Psychopharmacology 2007;189:
de Win MM, Jager G, Booij J, et al. Sustained effects of
ecstasy on the human brain: a prospective neuroimaging
study in novel users. Brain 2008;131(pt 11):2936–2945.
McCann UD, Ridenour A, Shaham Y, Ricaurte GA. Seroto-
nin neurotoxicity after(?/?)
humans. Neuropsychopharmacology 1994;10:129–138.
First MB, Spitzer RL, Gibbon M, Williams JB. Structured
Clinical Interview for DSM-IV Axis I Disorders (SCID-I),
clinician version. Arlington, VA: American Psychiatric
Publishing Inc; 1997.
Iber C, Ancoli-Israel S, Chesson AL, Quan SF. The AASM
Terminology, and Technical Specifications. Westchester, IL:
American Academy of Sleep Medicine; 2007.
Morgan MJ, Impallomeni LC, Pirona A, Rogers RD. Ele-
vated impulsivity and impaired decision-making in abstinent
Neurology 73December 8, 2009
ecstasy(MDMA)userscomparedtopolydruganddrug-naive Download full-text
controls. Neuropsychopharmacology 2006;31:1562–1573.
Quednow BB, Ku ¨hn KU, Hoppe C, Westheide J, Maier W,
Daum I, Wagner M. Elevated impulsivity and impaired
decision-making cognition in heavy users of MDMA (“ec-
stasy”). Psychopharmacology 2007;189:517–530.
McCann UD, Eligulashvili V, Mertl M, Murphy DL, Ricau-
rte GA. Altered neuroendocrine and behavioral responses to
m-chlorophenylpiperazine in 3,4-methylenedioxymetha-
mphetamine (MDMA) users. Psychopharmacology 1999;
Gerra G, Zaimovic A, Ferri M, et al. Long-lasting effects of
(?/?)3,4-methylenedioxymethamphetamine (ecstasy) on
serotonin system function in humans. Biol Psychiatry
Banks S, Dinges DF. Behavioral and physiological conse-
quences of sleep restriction. J Clin Sleep Med 2007;3:
Carskadon MA, Acebo C, Jenni OG. Regulation of adoles-
cent sleep: implications for behavior. Ann NY Acad Sci
O’Brien EM, Mindell JA. Sleep and risk-taking behavior
in adolescents. Behav Sleep Med 2005;3:113–133.
Carley DW, Paviovic S, Janelidze M, Radulovacki M.
Functional role for cannabinoids in respiratory stability
during sleep. Sleep 2002;25:391–398.
More Ways to Meet Your Maintenance of
New NeuroSAE™ Now Available!
Now you can get additional practice with the new 2008 version of the popular AAN NeuroSAE
(Neurology Self-Assessment Examination). The 2007 and 2008 versions of this unique practice test
are designed to help you meet the American Board of Psychiatry and Neurology (ABPN) self-
assessment requirement for Maintenance of Certification.
● Content outline based on the outline used for the ABPN’s cognitive examination for recertifi-
cation in clinical neurology
● 100 Multiple-choice questions help you determine strengths and areas for improvement
● Convenient—take online on your own schedule
● Receive feedback by subspecialty area and suggestions for further reading
● Compare your performance to other neurologists
● $99/examination for AAN members and $149/examination for nonmembers
Take one—or both—versions. Visit www.aan.com/neurosae today!
Neurology 73 December 8, 2009