Psychopharmacology
December 1, 2011
Roland R. Griffiths, Matthew W Johnson, William A Richards et al.
938 citations
Psilocybin can produce mystical-type experiences that lead to lasting positive changes in attitudes, mood, and behavior. In a double-blind study, 18 adults (17 with no prior hallucinogen use) received 0, 5, 10, 20, or 30 mg/70 kg psilocybin in five sessions under supportive conditions. At the two highest doses, 72% of volunteers reported a mystical-type experience, and 39% experienced extreme anxiety or fear. One month later, participants rated these sessions as having substantial personal and spiritual significance, with the ascending dose sequence showing greater positive effects. At 14 months, these positive ratings remained undiminished and were consistent with observer reports. The effects generally increased with dose.
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.
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.
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.
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.