Una Mccann

Una Mccann
Johns Hopkins Medicine | JHUSOM · Department of Psychiatry and Behavioral Sciences

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145
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Publications (145)
Article
Objective: Major depression is the most common psychiatric sequela of traumatic brain injury (TBI), but effective treatment continues to be a challenge, with few studies providing guidance. Methods: In a pilot study, the authors evaluated the effect size of low-frequency right-sided (LFR) repetitive transcranial magnetic stimulation (rTMS), comp...
Poster
Full-text available
Introduction Sleep disturbance is highly prevalent in traumatic brain injury (TBI). Approximately 30-70% of TBI patients report some type of sleep disruption. Nevertheless, studies that objectively characterize sleep in TBI are lacking. The present study employed multiple modalities to characterize sleep architecture and quality in patients with TB...
Article
There are limited data regarding the incidence of pathological laughter and crying (PLC) after traumatic brain injury (TBI). This study aimed to identify the occurrence of PLC in the first year after TBI and to determine whether there is a relationship between PLC and other clinical features or demographics. Subjects who sustained a first-time TBI...
Chapter
(±)3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a synthetic ring-substituted amphetamine analog that produces a unique blend of stimulant and psychedelic effects. Considerable research demonstrates that MDMA has the potential to damage brain serotonin (5-HT)-containing neurons in animals, and a growing body of data indicates that MDMA is al...
Article
Primary objective: To determine whether sleep disturbance in the acute post-traumatic brain injury (TBI) period predicts symptoms of depression, anxiety or apathy measured 6 and 12 months after TBI. Research design: Longitudinal, observational study. Methods and procedures: First time closed-head injury patients (n = 101) were recruited and ev...
Article
The neurotoxicity of ± 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is influenced by temperature and varies according to species. The mechanisms underlying these two features of MDMA neurotoxicity are unknown, but differences in MDMA metabolism have recently been implicated in both. The present study was designed to: 1) assess the effect of...
Article
Repeated doses of the popular recreational drug methylenedioxymethamphetamine (MDMA, 'Ecstasy') are known to produce neurotoxic effects on brain serotonin (5-HT) neurons but it is widely believed that typical single oral doses of MDMA are free of neurotoxic risk. Experimental and therapeutic trials with MDMA in humans are underway. The mechanisms b...
Article
A number of published studies have questioned the serotonin neurotoxic potential of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and related drugs (fenfluramine, p-chloroamphetamine) based upon results from Western blot studies using a custom synthesized serotonin transporter (SERT) antibody that found no reduction in the abundance of a 50kD...
Article
3,4-Methylenedioxymethamphetamine (MDMA)'s O-demethylenated metabolite, 3,4-dihydroxymethamphetamine (HHMA), has been hypothesized to serve as a precursor for the formation of toxic catechol-thioether metabolites (e.g., 5-N-acetylcystein-S-yl-HHMA) that mediate MDMA neurotoxicity. To further test this hypothesis, HHMA formation was blocked with dex...
Article
Full-text available
The extended-release formulation of zolpidem (Ambien CR) is approved for the treatment of insomnia without a treatment duration limit. Acutely zolpidem impairs performance, and no research to date has examined whether tolerance develops to these performance impairments during nighttime awakening. The present double-blind, placebo-controlled study e...
Article
Full-text available
The baboon is potentially an attractive animal for modeling 3,4-methylenedioxymethamphetamine (MDMA) effects in humans. Baboons self-administer MDMA, are susceptible to MDMA neurotoxicity, and are suitable for positron emission tomography, the method most often used to probe for MDMA neurotoxicity in humans. Because pharmacokinetic equivalence is a...
Article
Full-text available
The purpose of the present study was to determine if trihydroxymethamphetamine (THMA), a metabolite of methylenedioxymethamphetamine (MDMA, "ecstasy"), or its thioether conjugate, 6-(N-acetylcystein-S-yl)-2,4,5-trihydroxymethamphetamine (6-NAC-THMA), play a role in the lasting effects of MDMA on brain serotonin (5-HT) neurons. To this end, novel hi...
Article
Full-text available
This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Participants were 18 adults (17 hallucinogen...
Article
Mild traumatic brain injury (mTBI) is a complex entity with no known objective diagnostic markers. To test the hypothesis that sleep disturbances in the acute mTBI period can serve as an indicator of brain injury, the authors compared sleep polysomnograms (PSG) and sleep EEG power spectra (PS) data in seven mTBI subjects with seven age- and race-ma...
Article
(±)3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that has potential to damage brain serotonin (5-HT) neurons in humans. Brain 5-HT neurons play a role in pain modulation, yet little is known about long-term effects of MDMA on pain function. Notably, MDMA users have been shown to have altered sleep, a phenomenon that can le...
Article
Sleep difficulty is a common symptom of cannabis withdrawal, but little research has objectively measured sleep or explored the effects of hypnotic medication on sleep during cannabis withdrawal. Twenty daily cannabis users completed a within-subject crossover study. Participants alternated between periods of ad libitum cannabis use and short-term...
Article
Mild traumatic brain injury (mTBI) is a complex entity with no known objective diagnostic markers. To test the hypothesis that sleep disturbances in the acute mTBI period can serve as an indicator of brain injury, the authors compared sleep polysomnograms (PSG) and sleep EEG power spectra (PS) data in seven mTBI subjects with seven age- and race-ma...
Article
Full-text available
Previous studies have suggested a link between heart rate (HR) following trauma and the development of posttraumatic stress disorder (PTSD). This study expands on previous work by evaluating HR in burn patients followed longitudinally for symptoms of acute stress disorder (ASD) and PTSD. Data were collected from consecutive patients admitted to the...
Article
Full-text available
J. Neurochem. (2010) 114 , 1135–1142. Abstract It is widely believed that dopamine (DA) mediates methamphetamine (METH)‐induced toxicity to brain dopaminergic neurons, because drugs that interfere with DA neurotransmission decrease toxicity, whereas drugs that increase DA neurotransmission enhance toxicity. However, temperature effects of drugs th...
Article
Methylenedioxymethamphetamine (MDMA, "ecstasy") is a popular recreational drug of abuse and a selective brain serotonin neurotoxin. Functional consequences of MDMA neurotoxicity 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 p...
Article
Full-text available
Methylenedioxymethamphetamine (MDMA; "Ecstasy") is a popular recreational drug and brain serotonin (5-HT) neurotoxin. Neuroimaging data indicate that some human MDMA users develop persistent deficits in brain 5-HT neuronal markers. Although the consequences of MDMA-induced 5-HT neurotoxicity are not fully understood, abstinent MDMA users have been...
Article
Full-text available
Following an acute burn injury, higher distress is consistently observed among individuals exhibiting a conflict between approach coping (e.g., processing) and avoidance coping (e.g., suppression) relative to those individuals who use only one of these methods. Study objectives were to determine if contradictory coping messages would lead to such a...
Article
Full-text available
The mechanism by which the recreational drug (+/-)-3,4-methylenedioxymethamphetamine (MDMA) destroys brain serotonin (5-HT) axon terminals is not understood. Recent studies have implicated MDMA metabolites, but their precise role remains unclear. To further evaluate the relative importance of metabolites versus the parent compound in neurotoxicity,...
Article
The present study compared the disposition and metabolism of the recreational drug (±) 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of...
Article
Full-text available
(+/-)3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not know...
Article
At certain doses, the psychoactive drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") destroys brain serotonin axon terminals. By causing increases in plasma MDMA concentrations that exceed those predicted by the increase in dose, nonlinear pharmacokinetics has the potential to narrow the range between safe and neurotoxic doses of MDMA....
Article
Treatment for anxiety and post-traumatic stress disorder (PTSD) includes exposure therapy and medications, but some patients are refractory. Few studies of repetitive transcranial magnetic stimulation (rTMS) for anxiety or PTSD exist. In this preliminary report, rTMS was combined with exposure therapy for PTSD. Nine subjects with chronic, treatment...
Article
Studies in abstinent methamphetamine (METH) users have demonstrated reductions in brain dopamine transporter (DAT) binding potential (BP), as well as cognitive and motor deficits, but it is not yet clear whether cognitive deficits and brain DAT reductions fully reverse with sustained abstinence, or whether behavioral deficits in METH users are rela...
Article
In recent years, there has been growing interest in the use of Western blot analysis to monitor changes in the abundance of the serotonin transporter (SERT) protein. In the Western blot procedure, heat denaturation is a common, early step. We now report that heating samples to 90 degrees C decreases the abundance of the SERT protein band and causes...
Article
(+/-) 3, 4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug of abuse and a brain serotonin (5-HT) neurotoxin in animals. Growing evidence suggests that humans who use MDMA recreationally can also develop 5-HT neurotoxic injury, although functional consequences have been difficult to identify. Twenty-five abstinent MDMA users and...
Article
This study investigated the prevalence of symptoms of depression in patients hospitalized with severe burns and the association of symptoms of depression in the hospital with physical health 2 months after discharge, controlling for pre-burn physical health as measured by the SF-36 physical composite score. Survivors of acute burns were evaluated d...
Article
Full-text available
We studied in vivo expression of the serotonin transporter (SERT) protein after 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine (PCA), or fenfluramine (FEN) treatments, and compared the effects of substituted amphetamines to those of 5,7-dihydroxytryptamine (5,7-DHT), an established serotonin (5-HT) neurotoxin. All drug treatments pro...
Article
Full-text available
Impaired central pain modulation is implicated in the pathophysiology of chronic pain. In this controlled experiment, we evaluated whether partial sleep loss altered endogenous pain inhibition and reports of spontaneous pain. Thirty-two healthy females were studied polysomnographically for 7 nights. On Nights 1-2 (Baseline), subjects slept undistur...
Article
Authors conducted a systematic review to assess performance characteristics of depression screening instruments after acute myocardial infarction (AMI). Among the seven studies identified, the Beck Depression Inventory (BDI) and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) were used most frequently. Studies were gen...
Article
The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997. Both drugs are known to have the potential to damage brain serotonin (5-HT) axons and axon terminals in animals, including nonhuman primates. This study used quantitative positron emission tomography (PET) with [(11)C] M...
Article
Full-text available
Abuse of stimulant drugs invariably leads to a disruption in sleep-wake patterns by virtue of the arousing and sleep-preventing effects of these drugs. Certain stimulants, such as 3,4-methylenedioxymethamphetamine (MDMA), may also have the potential to produce persistent alterations in circadian regulation and sleep because they can be neurotoxic t...
Article
Full-text available
We studied in vivo expression of the serotonin transporter (SERT) protein after 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine (PCA), or fenfluramine (FEN) treatments, and compared the effects of substituted amphetamines to those of 5,7-dihydroxytryptamine (5,7-DHT), an established serotonin (5-HT) neurotoxin. All drug treatments pro...
Article
Full-text available
Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions. The par...
Article
To examine the relationship between temperature (ambient and core), dopaminergic neurotoxicity, and plasma drug [methamphetamine (METH)] and metabolite [amphetamine (AMPH)] concentrations, two separate groups of squirrel monkeys (n = 4-5 per group) were treated with METH (1.25 mg/kg, given twice, 4 h apart) or vehicle (same schedule) at two differe...
Article
Full-text available
The increasing use of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) in the setting of large dance parties ('raves') and clubs has been the source of some concern, because of potential acute adverse events, and because animal studies suggest that MDMA has the potential to damage brain serotonin (5-HT) neurons. However, it is not yet known whether M...
Article
A large body of data indicates that (+/-)3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can damage brain serotonin neurons in animals. However, the relevance of these preclinical data to humans is uncertain, because doses and routes of administration used in animals have generally differed from those used by humans. Here, we examined the pharm...
Article
Full-text available
Pharmacotherapy with amphetamine is effective in the management of attention-deficit/hyperactivity disorder (ADHD), now recognized in adults as well as in children and adolescents. Here we demonstrate that amphetamine treatment, similar to that used clinically for adult ADHD, damages dopaminergic nerve endings in the striatum of adult nonhuman prim...
Article
Full-text available
(+/-)3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') is a widely used illicit drug that produces toxic effects on brain serotonin axons and axon terminals in animals. The results of clinical studies addressing MDMA's serotonin neurotoxic potential in humans have been inconclusive. In the present study, 23 abstinent MDMA users and 19 non-MDMA co...
Article
Full-text available
Sleep-deprivation experiments suggest that sleep loss increases pain sensitivity. It is unclear from preliminary studies, however, whether sleep-related processes are directly associated with pain perception or whether hyperalgesia is due to the secondary effects of sleep deprivation and/or demand characteristics. Consequently, we sought to evaluat...
Article
The relationship between baseline depression and health-related quality of life were examined in a cohort of patients after hospitalization due to acute myocardial infarction (N=196). Patients were assessed for presence of mood disturbance, anxiety, and quality of life at the time of hospitalization and again 4 months later. Baseline assessment was...
Article
Use of illicit drugs in clubs and large dance parties (so-called raves) is a burgeoning cultural trend. Such recreational drug use is associated with several medical complications, both acute and longlasting. Although few, if any, of the drugs currently used in recreational venues are truly new, their patterns and context of use have changed (a gre...
Article
Full-text available
The objective of this study was to determine the ability of cardiovascular healthcare workers to assess the presence or absence of symptoms of depression in patients hospitalized with acute myocardial infarction (AMI) in the absence of formal screening. Patients admitted with AMI underwent screening using the Beck Depression Inventory (BDI) adminis...
Article
Full-text available
Focus Points • There is growing evidence that anxiety is an independent risk factor for the development of cardiovascular disease. • Anxiety following a major cardiac event can impede recovery and is associ-ated with a higher morbidity and mortality. • First-line treatment of anxiety in patients with cardiac disease should con-sist of psychoeducati...
Article
Full-text available
In mice, the recreational drug (+/-)3,4-methylenedioxymethamphetamine [MDMA ("ecstasy")] produces a selective toxic effect on brain dopamine (DA) neurons. Using cDNA microarray technology in combination with an approach designed to facilitate recognition of relevant changes in gene expression, the present studies sought to identify genes potentiall...
Article
In addition to the social, cultural and indirect medical complications of amphetamine analog abuse, this class of drugs is also known to have the potential to damage brain monoaminergic cells directly. Using methamphetamine as a prototype, this article provides a brief review of the history of amphetamine neurotoxicity research and the progress tha...
Article
El incremento del consumo de éxtasis (MDMA) por parte de los jóvenes ha obligado al estudio de efectos a corto y medio plazo sobre el SNC. En la última década, se demostró la existencia de neurotoxicidad serotoninérgica en el SNC. Recientemente aparecieron estudios tendentes a demostrar también daño dopaminérgico que se ha evidenciado en experiment...
Article
Little is known about serotonin neurons in Parkinson disease (PD). To study the serotonin system in PD with positron emission tomography, using the serotonin transporter radioligand [11C](+)McN5652. We measured the density of the serotonin transporter and the density of [11C]WIN35,428-labeled dopamine transporters in the striatum of 13 adults with...
Article
Responds to comments by M. Mithoefer, et al (see record 2003-06079-001) on the article by G. A. Ricaurte, et al (see record 2002-18729-002) which reported dopamine neurotoxicity in primates injected repeatedly with MDMA. The original authors remain of the opinion that there are not sufficient data to conclude that clinical MDMA research can be cond...
Article
It has been suggested that pharmacological challenges that induce panic attacks are confounded by effects of environmental stress, elevated baseline arousal, and expectancy bias. To control for effects of arousal and cognition on the panicogenic effects of pentagastrin, pharmacological challenges were conducted during sleep in seven patients with p...
Article
The present studies were conducted to further explore the potential role of metabolic compromise in substituted amphetamine-induced serotonin (5-HT) neurotoxicity. To this end, we examined the glucoprivic effects of 2-deoxy-D-glucose (2-DG) on the 5-HT neurotoxic effects of fenfluramine (FEN) and methylenedioxymethamphetamine (MDMA). Rats were trea...
Article
Low levels of serotonin may reduce the density of the serotonin transporter (SERT) by either increasing trafficking or reducing synthesis; a "neuroadaptive response". To determine whether 3,4-methylenedioxymethamphetamine (MDMA)-induced reductions in SERT density could be related to such a mechanism, p-chlorophenylalanine or MDMA was administered t...
Article
The prevailing view is that the popular recreational drug (±)3,4-methylenedioxymethamphetamine (MDMA, or “ecstasy”) is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in ad...
Article
To measure the prevalence of 3,4-methylenedioxymethamphetamine (MDMA) and other drug use in young males entering compulsory military service in Asturias (northern Spain) and to define trends in MDMA use in this group during the period from 1995 to 1999. We also sought to determine whether MDMA users have distinct personality features or higher leve...
Article
Full-text available
There has been considerable interest in the development of a PET radioligand selective for the serotonin (5-hydroxytryptamine [5-HT]) transporter (SERT) that can be used to image 5-HT neurons in the living human brain. The most widely used SERT radiotracer to date, trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl[pyrrolo-[2,1-a]isoquinolin...
Article
Full-text available
Aim: To measure the prevalence of 3,4-methylenedioxymethamphetamine (MDMA) and other drug use in young males entering compulsory military service in Asturias (northern Spain) and to define trends in MDMA use in this group during the period from 1995 to 1999. We also sought to determine whether MDMA users have distinct personality features or higher...
Article
The mechanism by which 3,4-methylenedioxymethamphetamine (MDMA) produces serotonin (5-HT) neurotoxicity is unknown but considerable evidence suggests that endogenous brain dopamine (DA) is involved. However, it has recently become apparent that some of the data implicating brain DA in MDMA neurotoxicity may be confounded by drug effects on thermore...
Article
3,4-Methylenedioxymethamphetamine ("Ecstasy," MDMA) and fenfluramine, widely used by humans, are potent brain serotonin (5-HT) neurotoxins in animals. Thus, there is concern that humans previously exposed to these amphetamine derivatives may have incurred brain 5-HT neurotoxicity. However, assessing the status of brain 5-HT neurons in the living or...
Article
Establishing functional deficits as a result of neurotoxic dosing regimens of MDMA has been difficult. However, moderate success has been achieved when sensitive animal models and drug challenge have been used together. The present study used a repeated-acquisition technique and dose-effect determinations before, during and after neurotoxic MDMA ex...
Article
Full-text available
The purpose of these studies was to examine the role of gene expression in methamphetamine (METH)-induced dopamine (DA) neurotoxicity. First, the effects of the mRNA synthesis inhibitor, actinomycin-D, and the protein synthesis inhibitor, cycloheximide, were examined. Both agents afforded complete protection against METH-induced DA neurotoxicity an...
Article
Rationale: Establishing functional deficits as a result of neurotoxic dosing regimens of MDMA has been difficult. However, moderate success has been achieved when sensitive animal models and drug challenge have been used together. Objective: The present study used a repeated-acquisition technique and dose-effect determinations before, during and af...
Chapter
(±) 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) is an increasingly popular drug of abuse in the United States, Europe, and Australia (1–3). MDMA is a synthetic amphetamine analog that bears structural similarity to both the psychomotor stimulant, amphetamine, and the hallucinogen, mescaline. MDMA users report that in addition to having some...
Article
Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mes...
Article
THE ARTICLE by Reneman et al1 in this issue of the ARCHIVES is timely and provocative and highlights several areas of controversy in the fields of substance abuse, drug-induced neurotoxic effects, and neuroimaging. The authors present evidence that the illicit recreational drug 3,4-methylenedioxymethamphetamine (MDMA, or "ecstasy") may cause persis...
Article
Nuclear imaging studies have examined cerebral blood flow (rCBF) in subjects with posttraumatic stress disorder (PTSD) using symptom evocation paradigms. To date, no such studies have investigated rCBF as related to subjects' reports of flashback intensity. Subjects with varying traumatic histories and longstanding PTSD were studied using [15O]-H2O...
Article
Although the neurotoxic potential of methamphetamine (METH) is well established, underlying mechanisms have yet to be identified. In the present study, we sought to determine whether ionic dysregulation was a feature of METH neurotoxicity. In particular, we reasoned that if METH impairs the function of Na(+)/H(+) and/or Na(+)/Ca(2+) antiporters by...
Article
The present studies examined the role of endogenous dopamine (DA) in methamphetamine (METH)-induced dopaminergic neurotoxicity while controlling for temperature-related neuroprotective effects of the test compounds, reserpine and alpha-methyl-p-tyrosine (AMPT). To determine if the vesicular pool of DA was essential for the expression of METH-induce...
Article
Although the neurotoxic potential of methamphetamine (METH) is well established, underlying mechanisms have yet to be identified. In the present study, we sought to determine whether ionic dysregulation was a feature of METH neurotoxicity. In particular, we reasoned that if METH impairs the function of Na+/H+ and/or Na+/Ca2+ antiporters by compromi...