Human Psychopharmacology Clinical and Experimental
December 1, 2001
A. C. Parrott
349 citations
MDMA (Ecstasy) is an illegal drug that increases serotonin and other neurotransmitter activity, producing euphoria, hyperactivity, and hyperthermia, especially in hot, crowded settings. Around 80% of users experience rebound depression and lethargy days after use. Repeated use causes tolerance and, in animals, serotonergic neurotoxicity. In humans, heavy users show reduced serotonin markers and deficits in memory, cognition, sleep, appetite, and sexual interest, which persist long after stopping use, suggesting permanent neuropharmacological damage.
Journal of Psychopharmacology
January 1, 2005
A. C. Parrott
241 citations
Chronic tolerance to MDMA (Ecstasy) is well-documented: novice users typically take one tablet per session, regular users two to three, and experienced users may take ten to twenty-five tablets. Users often report reduced subjective effects with repeated use, leading to dose escalation and binge patterns such as stacking multiple tablets or boosting successive doses. Some experienced users snort or inject MDMA. Chronic tolerance and bingeing are statistically linked to higher rates of drug-related psychobiological problems. Neuroadaptive processes are involved, but evidence on hepatic and behavioral mechanisms is lacking. Animal research suggests serotonergic neurotoxicity from intensive dosing may contribute, potentially explaining parallel declines in efficacy, dose escalation, and rising problems. The underlying mechanisms remain unclear, with serotonergic neurotoxicity as a possible novel cause.
Journal of Psychopharmacology
January 1, 1998
A. C. Parrott, A. J. Lees, N. J. Garnham et al.
226 citations
Regular and novice users of MDMA (ecstasy) showed similar performance to non-users on tests of reaction time and vigilance, but both user groups recalled significantly fewer words than controls on immediate and delayed word recall tasks. The study involved 10 regular users (10+ lifetime uses), 10 novice users (1-9 uses), and 10 never-users. These memory deficits align with animal research suggesting MDMA may cause serotonergic damage in brain regions critical for memory, such as the hippocampus and frontal cortex.
Human Psychopharmacology Clinical and Experimental
July 1, 2013
A. C. Parrott
184 citations
MDMA, initially considered a novel psychoactive substance with low abuse potential due to loss of efficacy, is now understood to cause widespread neuropsychobiological damage. Recreational users show a pattern of increasing doses and deteriorating cost-benefit ratios. MDMA elevates body temperature and thermal stress, and can increase cortisol levels by 800% in dance clubbers. It can be extremely euphoric but also intensifies negative moods. The drug causes apoptosis and has been investigated for cancer therapy due to anti-lymphoma properties. Users exhibit deficits in memory, higher cognition, problem solving, and social intelligence, while basic cognitive skills remain intact.
Human Psychopharmacology Clinical and Experimental
July 12, 2002
A. C. Parrott, Tom Buchanan, Andrew Scholey et al.
163 citations
Depression, memory problems, anxiety, mood fluctuation, poor concentration, infections, tremors/twitches, and weight loss are all more common among people who have used Ecstasy more often. In a survey of 282 Ecstasy users, memory problems attributed to the drug were reported by 19% of novice users (1–9 occasions), 52% of moderate users (10–99 occasions), and 73% of heavy users (100+ occasions). The incidence of psychobiological problems attributed to Ecstasy use increases directly with the number of times it has been used.
Neuropsychobiology
January 1, 2000
A. C. Parrott
153 citations
Repeated use of MDMA (Ecstasy) can damage serotonin-producing neurons in laboratory animals, and a similar pattern may occur in humans. A review of drug-free recreational Ecstasy users found consistent impairments in three cognitive areas: memory for new information, higher-level executive processing, and increased impulsivity. Basic cognitive functions like reaction time, vigilance, and Stroop performance remained intact. Some users reported memory and concentration problems they attributed to MDMA. Methodological issues, such as non-random assignment and other drug use, complicate the findings. The pattern of deficits matches animal data showing serotonergic damage in the frontal cortex and hippocampus, and aligns with a hypothetical construct of reduced cortical inhibition.
Neuropsychobiology
January 1, 2004
A. C. Parrott
152 citations
MDMA, also known as ecstasy, is an amphetamine derivative widely used recreationally, especially at dances and raves. Animal research shows that hot temperatures and crowding amplify MDMA's acute effects, increase social interaction and drug self-administration, and impair thermal control, causing overheating. In humans, acute medical dangers involve hyperthermia-related reactions that typically occur in hot, crowded environments. MDMA is a serotonergic neurotoxin in animals, and heat and crowding worsen axon loss; if this applies to humans, club conditions may raise the risk of adverse neuropsychological effects. Self-reported dancing or exercise while on MDMA is linked to more subsequent psychobiological problems.
Human Psychopharmacology Clinical and Experimental
May 1, 1997
D. Davison, A. C. Parrott
136 citations
Twenty recreational drug users described the psychological and physiological effects of MDMA. On the drug, they reported increased elation, agreeableness, energy, mental confusion, faster heart rate, feeling hot, sweating, dehydration, dilated pupils, and tight jaw. Coming off the drug led to lethargy, moodiness, insomnia, depression, irritability, and paranoia. 25 percent of the sample reported bad trips. Chronic tolerance was not apparent, but acute tolerance was evident, with a necessary period between doses to maintain effectiveness, which may help explain MDMA's low addiction potential.
Human Psychopharmacology Clinical and Experimental
December 1, 2001
Kirstie Soar, John Turner, A. C. Parrott
80 citations
A review of psychiatric case studies from the last 10 years finds that MDMA (Ecstasy) is strongly linked to the onset of psychological disorders and persistent psychiatric symptoms. Only 24% of patients had a previous psychiatric history, and 34% had a psychiatric illness among first-degree relatives. The substantial proportion of patients without such history, along with the temporal relationship between MDMA use and recurring symptoms, suggests a causal role of the drug. Supporting evidence from non-clinical samples shows that Ecstasy users have higher scores on SCL-90 subscales compared to non-users, with heavier users showing more pathology.
Neurotoxicology and Teratology
March 5, 2012
Lynn T. Singer, David G. Moore, Sarah Fulton et al.
77 citations
MDMA (Ecstasy) use during pregnancy is linked to poorer motor quality and lower milestone attainment in infants at 4 months, with a dose-response relationship: greater exposure corresponds to worse motor outcomes. This first prospective study of prenatal MDMA exposure in humans compared 28 women who used MDMA during pregnancy with 68 polydrug-using women who did not, controlling for confounding factors. MDMA-using mothers had fewer prior births and more health, work, and social problems. Exposed infants were more likely to be male. The findings suggest risk to the developing infant and indicate that continued follow-up is needed to determine whether early motor delays persist or resolve.
Neuropsychobiology
January 1, 2008
A. C. Parrott, Jing Zhan Lock, A.c. Conner et al.
77 citations
Recreational Ecstasy users showed an 800% increase in cortisol and a 75% increase in testosterone when dancing at a club on MDMA, but no such changes occurred when they danced at the same club without the drug. Body temperature did not change significantly, though a borderline trend for higher values appeared after MDMA. Feelings of happiness and excitement increased under MDMA but were not significantly greater than during abstinence. The findings suggest that neurohormonal release is a key part of the acute MDMA experience and support a bioenergetic stress model of recreational use.
Journal of Psychopharmacology
March 30, 2006
Kirstie Soar, John Turner, A. C. Parrott
65 citations
People who report problems from their ecstasy use show higher levels of psychiatric symptoms such as depression, anxiety, and somatization compared to those who use ecstasy without problems, polydrug users, and people who have never used illegal drugs. In contrast, non-problematic ecstasy users do not differ from controls on these measures. Problematic users also report greater lifetime consumption, average dosage, and binge use, and are more likely to have personal and family psychiatric histories. The findings suggest that ecstasy-related psychological problems are linked to dosage and pre-existing mental health vulnerabilities, not ecstasy use alone.
Journal of Psychoactive Drugs
January 1, 2014
A. C. Parrott
60 citations
MDMA has properties that could aid psychotherapy, but its effects are complex and not always beneficial. The drug acts as an entactogen, promoting feelings of love and warmth, yet it can also trigger negative experiences because it non-selectively releases thoughts and emotions—similar to LSD. Acutely, MDMA alters hormone levels, raising cortisol, oxytocin, and testosterone; oxytocin may help therapy, while cortisol can increase stress. After use, a neurochemical recovery period often brings lethargy and depression due to low serotonin. Regular use risks serotonergic neurotoxicity, memory problems, and other psychobiological issues. Proponents argue MDMA-assisted therapy should be limited to reactive disorders like PTSD, as it may worsen distress in those with prior psychiatric conditions.
British Journal of Pharmacology
March 9, 2012
A. C. Parrott
50 citations
A commentary argues that MDMA (ecstasy) is clearly damaging to humans, contradicting the claim that animal data cannot predict its adverse effects and that MDMA does not produce serotonin neurotoxicity in the human brain. Neuroimaging studies worldwide consistently show reduced levels of the serotonin transporter (SERT) across higher brain regions in abstinent recreational users, even after controlling for confounds. These SERT reductions correlate with impairments in memory and higher cognition. The author contends that extensive empirical data demonstrate both structural and functional deficits from MDMA use in humans.
PEDIATRICS
August 21, 2012
Lynn T. Singer, David G. Moore, Meeyoung O. Min et al.
49 citations
Heavier prenatal exposure to MDMA (ecstasy) predicted poorer mental and motor development in 12-month-old infants, with motor delays appearing in a dose-dependent manner. Lighter-exposed infants were comparable to nonexposed infants. No effects were found on language, emotional regulation, or parenting stress. The study involved 96 women in the United Kingdom—28 who used MDMA during pregnancy and 68 who did not—and used standardized developmental assessments.
Neuropsychobiology
October 20, 2010
Andrew Scholey, Lauren Owen, J. R. Gates et al.
46 citations
Among 49 undergraduate volunteers, self-reported Ecstasy use closely matched MDMA traces found in hair samples. Both self-report and hair analysis predicted lower happiness and higher stress ratings. Self-reported use, but not hair analysis, was also linked to lower tension. The findings suggest the Internet can effectively complement traditional laboratory studies on recreational drug effects.
Behavioural Pharmacology
July 11, 2014
A. C. Parrott, Catharine Montgomery, Mark Wetherell et al.
34 citations
Recreational use of MDMA (ecstasy) increases cortisol levels, a marker of stress, both immediately and over longer periods. In laboratory settings, acute use raises cortisol by 100-200%, while dance clubbers combining the drug with dancing experience an 800% increase. Abstinent users' three-month hair samples show cortisol levels 400% higher than controls. Chronic users exhibit heightened cortisol in stressful settings, deficits in complex cognitive tasks, and altered brain activation patterns suggesting increased mental effort. Mood deficits include more daily stress and higher depression in susceptible individuals. Changes in the hypothalamic-pituitary-adrenal (HPA) axis may explain these neuropsychobiological stress effects.
Neuropsychobiology
January 1, 2000
John Turner, A. C. Parrott
27 citations
Experts from diverse fields—animal neuroscience, human cognitive testing, police pathology, psychotherapy, and psychiatry—debated whether MDMA is a human neurotoxin. Some highlighted methodological weaknesses in human studies, such as uncertain tablet contents, reliance on self-reports, and confounding factors like heat, exertion, poor diet, and other drugs, which could mimic neural damage. The absence of gliosis in animal models suggested alternative interpretations for observed neural changes. Others noted no neural or behavioral change after a single dose and pointed to therapeutic benefits in supportive settings. However, novel studies across several European countries confirmed cognitive, behavioral, EEG, and neurological deficits in drug-free Ecstasy users, even after controlling for other drug use. The conclusion: if MDMA neurotoxicity is a myth, it is one with a heavy serotonergic component.
Human Psychopharmacology Clinical and Experimental
September 1, 1997
A. C. Parrott, Marta Stuart
24 citations
Twenty-one recreational polydrug users aged 17–34 reported their typical feeling states while on MDMA (Ecstasy), LSD, and amphetamine using a modified Profile of Mood States questionnaire. For three mood factors, MDMA produced intermediate effects: feelings of energy, confidence, and clearheadedness were highest under amphetamine, lowest on LSD, and intermediate after Ecstasy. However, MDMA's mood profile was more unique in other respects, with significantly higher feelings of elation, agreeableness, and composure than the other two drugs.