Johns Hopkins Medicine
14 papers in the library · 2,676 citations · publishing 1988-2013
Neurology December 1, 1998 Karen I. Bolla, Una D. Mccann, George A. Ricaurte 376 citations
People who have stopped using MDMA show deficits in both verbal and visual memory. The severity of these memory problems is linked to how much MDMA they used in the past and to lower levels of serotonin activity in the brain, measured by a serotonin metabolite in spinal fluid.
Journal of Neuroscience June 15, 1999 George Hatzidimitriou, Una D. Mccann, George A. Ricaurte 338 citations
Seven years after treatment with MDMA (Ecstasy), squirrel monkeys still showed abnormal brain serotonin innervation patterns, though deficits in some regions were less severe than those observed at 18 months. No loss of serotonin nerve cell bodies in the rostral raphe nuclei was found, indicating that the abnormal patterns are not due to the loss of a particular cell group. Factors influencing recovery of injured serotonin axons include the distance of the affected terminal field from the raphe nuclei, the degree of initial injury, and possibly proximity to myelinated fiber tracts. Additional studies are needed to understand these factors and whether findings apply to humans.
Addiction May 1, 1994 Thomas Steele, Una D. Mccann, George A. Ricaurte 295 citations
MDMA (Ecstasy) produces a mix of stimulant and psychedelic effects mediated by brain monoamines, especially serotonin and dopamine. It also shows toxic activity toward brain serotonin neurons in animals, including non-human primates, at doses close to those used by humans. Whether MDMA is neurotoxic in humans remains under investigation, but documented adverse effects include systemic complications and neuropsychiatric consequences involving mood, cognition, and anxiety. Because MDMA use is restricted, retrospective clinical observations are a primary source of human data. This article reviews MDMA's behavioral pharmacology and toxicology to help clinicians recognize MDMA-related syndromes and understand serotonin's role in health and disease.
JAMA July 1, 1988 George A. Ricaurte 294 citations
MDMA, also known as ecstasy, is used recreationally and has been proposed as a therapy aid. In monkeys given repeated doses of 2.50, 3.75, or 5.00 mg/kg subcutaneously, the drug caused a dose-related depletion of serotonin and its metabolite 5-hydroxyindoleacetic acid across all brain regions examined two weeks later. These chemical deficits were accompanied by structural damage to serotonergic nerve fibers and pathological changes in nerve cell bodies within the dorsal raphe nucleus, but not the median raphe nucleus. The findings indicate MDMA acts as a selective serotonergic neurotoxin in nonhuman primates, suggesting humans using the drug may risk central serotonergic neuronal damage.
Neuropsychobiology January 1, 2000 George A. Ricaurte, Jie Yuan, Una D. Mccann 291 citations
MDMA, or 'Ecstasy', is a potent and selective neurotoxin for brain serotonin neurons in animals, as shown by neurochemical, neuroanatomical, and functional measures. New data indicate that MDMA reduces levels of the type 2 vesicular monoamine transporter, further supporting its serotonin neurotoxic potential. Using interspecies scaling, the authors demonstrate that dosages of MDMA known to be neurotoxic in animals fall squarely within the range used by recreational human users, countering the argument that animal dosages are too high to be relevant.
Neuropsychobiology January 1, 2000 Una D. Mccann, Victoria Eligulashvili, George A. Ricaurte 192 citations
MDMA (Ecstasy) is a brain serotonergic neurotoxin in animals, including nonhuman primates. Recreational doses overlap with those causing serotonin neurotoxicity in animals. Human MDMA users show selective decreases in cerebrospinal fluid 5-hydroxyindoleacetic acid and brain serotonin transporters, similar to neurotoxicity seen in nonhuman primates. Functional abnormalities possibly related to serotonin injury include cognitive deficits, altered sleep architecture, altered neuroendocrine function, altered behavioral responses to serotonin-selective drugs, and increased impulsivity. Further animal, longitudinal, and epidemiological studies are needed to confirm these findings and assess whether users face increased risk of neuropsychiatric illness with age.
Science September 27, 2002 George A. Ricaurte, Jie Yuan, George Hatzidimitriou et al. 179 citations
The recreational drug MDMA (ecstasy) is widely believed to selectively damage serotonin neurons in animals and possibly humans. However, nonhuman primates given several sequential doses of MDMA—a pattern similar to human use—developed severe damage to brain dopamine neurons, along with milder serotonin damage. This dopamine loss was linked to increased vulnerability to movement problems. The findings suggest that recreational MDMA users may unknowingly risk developing neuropsychiatric disorders related to dopamine or serotonin deficiency, either as young adults or later in life.
The American Journal of Drug and Alcohol Abuse January 1, 1992 John H. Krystal, Lawrence H. Price, Charles Opsahl et al. 171 citations
Chronic use of MDMA (ecstasy) is associated with mild-to-moderate impairments in memory, as measured by the Wechsler Memory Scale, even when no memory deficits are apparent on clinical examination. In a study of nine individuals with extensive MDMA use, eight showed at least mild impairment on one or more neuropsychological tests. Despite previous evidence suggesting serotonin deficits in this group, none reported depressed mood or met criteria for an affective disorder at the time of testing. These findings raise concern about potential detrimental effects of MDMA on cognitive function and highlight important issues regarding serotonin's role in cognition and mood regulation.
Synapse June 1, 1998 Ursula Scheffel, Zsolt Szabó, William B. Mathews et al. 146 citations
A single baboon treated with MDMA (5 mg/kg twice daily for four days) showed large decreases in serotonin transporter binding in all brain regions when scanned with PET and a serotonin-specific tracer 13 to 40 days later. Reductions ranged from 44% in the pons to 89% in the occipital cortex. Tracers for dopamine transporters showed no changes. At 9 and 13 months, some brain regions partly recovered serotonin transporter levels while others, such as the neocortex, remained persistently low. These findings demonstrate that PET can detect MDMA-induced damage to serotonin neurons in living primates and suggest the method could be used to test whether human MDMA users experience similar neurotoxicity.
Journal of Clinical Psychopharmacology October 1, 1991 Una D. Mccann, George A. Ricaurte, Domenic A. Ciraulo 137 citations
Two people who took large doses of MDMA, a recreational amphetamine analog, developed long-lasting neuropsychiatric syndromes. These cases suggest that MDMA, which is known to damage serotonin neurons in animals, may also cause harmful effects in humans. The evidence indicates that ingesting large amounts of MDMA can lead to lasting adverse functional consequences in vulnerable individuals.
SLEEP September 1, 1993 Richard P. Allen, Una D. Mccann, George A. Ricaurte 113 citations
MDMA, a recreational drug that damages serotonin neurons in animals, is linked to persistent sleep disturbances in humans. Comparing all-night sleep recordings of 23 MDMA users with 22 matched controls, MDMA users averaged 19 minutes less total sleep and 23.2 minutes less non-REM (NREM) sleep, primarily due to 37 minutes less stage 2 sleep. No significant differences appeared in stages 1, 3, or 4. While the cause—whether serotonin neurotoxicity—remains unknown, the findings suggest MDMA use can lead to lasting changes in brain structures governing sleep.
Addiction Biology June 14, 2013 Sarah Bradbury, Judith Bird, Joyce Colussi‐mas et al. 59 citations
About half of rats fail to acquire MDMA self-administration, and the difference is not due to how the drug is metabolized. MDMA triggers greater release of serotonin than dopamine in the brain. Rats that did acquire self-administration showed lower serotonin overflow than those that did not. Destroying serotonin neurons with a toxin made more rats acquire MDMA self-administration and speeded acquisition of cocaine self-administration. These findings suggest that serotonin limits initial sensitivity to MDMA's rewarding effects and delays reliable self-administration.
The Scientific World JOURNAL January 1, 2007 Una D. Mccann, George A. Ricaurte 52 citations
Abusing stimulant drugs like MDMA disrupts sleep-wake patterns because they promote arousal and prevent sleep. MDMA can also damage brain serotonin neurons in animals and possibly humans, and serotonin helps regulate sleep and circadian rhythms. People with MDMA-induced serotonin damage may develop chronic sleep and circadian problems, which could contribute to other issues like memory disturbances seen in abstinent users. This review examines preclinical and clinical studies on how prior MDMA exposure affects sleep, circadian activity, and the circadian pacemaker, identifies knowledge gaps, and suggests future research directions.
Synapse September 5, 2002 Liesbeth Reneman, Jan Booij, Jan B. A. Habraken et al. 33 citations
SPECT imaging with [123I]β-CIT can detect reductions in serotonin transporter density caused by MDMA neurotoxicity. A rhesus monkey treated with MDMA showed a 39% decrease in SERT binding in the hypothalamic/midbrain region 31 days after treatment, matching autoradiography data (−34%). Rat studies confirmed significant binding reductions in SERT-rich regions one week after neurotoxic MDMA doses. The findings validate [123I]β-CIT SPECT as a method for measuring MDMA-induced serotonergic damage in the brain.