Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research

Parrott, Andrew C.

doi:10.1002/hup.2318

Cited by 163 publications

(172 citation statements)

References 151 publications

(249 reference statements)

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“…While some proponents recommend MDMA at 1.5-1.7 mg/kg for treatment of PTSD Vollenweider et al, 2002), recreational users generally consume ϳ1.0 -3.0 mg/kg (Baylen and Rosenberg, 2006;Dumont and Verkes, 2006;Parrott, 2013). It is not unusual, however, for experienced MDMA users to take higher doses in an attempt to overcome tolerance to the drug's subjective effects (Parrott, 2013). Similar to the slow development of hyperthermia in rats, the desired psychoactive effects of oral MDMA in human users develop with relatively long latencies that could lead to multiple drug dosing.…”

Section: Translational Relevancementioning

confidence: 99%

“…MDMA is a Schedule I controlled substance in the United States and under similar restrictions in most Western countries, but whether MDMA is harmful remains a contentious issue (Pentney, 2001;Check, 2004;Parrott, 2013). Initial studies in human and laboratory animals showed that MDMA exposure can induce life-threatening health complications, including fatal hyperthermia (Gordon et al, 1991;Ricaurte et al, 2000;Kalant, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

Kiyatkin

Kim

Wakabayashi

et al. 2014

Journal of Neuroscience

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MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed "rave" parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses.Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22Ϫ23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity-and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ϳ1/5 of LD 50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues.

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Section: Translational Relevancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

Kiyatkin

Kim

Wakabayashi

et al. 2014

Journal of Neuroscience

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“…These highly variable MDMA-induced temperature responses, ranging from barely detectable increases to pathological hyperthermia, are also typical in humans; the same drug dose could have minimal or no adverse effects in some individuals, but serious life-threatening complications in others (Kalant, 2001;Parrott, 2013a). Our study focused on acute MDMA intoxication, but heightened brain temperature can also cause long-term changes in neural functions, as found in both preclinical studies and human research (Malberg and Seiden, 1998;Parrott and Young, 2014).…”

Section: Conclusion and Translational Relevancementioning

confidence: 99%

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction

Kiyatkin

Ren

Wakabayashi

et al. 2015

Neuropsychopharmacol

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MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (42.5°C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

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“…In humans, MDMA-related reductions of 5-HT transporters in different regions of the basal ganglia and the neocortex have been reported analogously (for review see Roberts et al, 2016b). Over the past three decades, the behavioral effects of MDMA use have been investigated extensively, and a broad range of cognitive dysfunctions has been reported in long-term MDMA users (Parrott, 2013).…”

Section: Introductionmentioning

confidence: 97%

“…While declarative memory impairments have been consistently shown in MDMA users with moderate to large effect sizes (for review see Kalechstein et al, 2007;Parrott, 2013), other cognitive domains yielded inconclusive results. The meta-analysis from Laws and Kokkalis (2007) found a medium effect size (d=0.63) for working memory (short-term memory) deficits in recreational MDMA users, but also reported that impairments are likely driven by verbal working memory deficits, whereas visual working memory may be primarily affected by cannabis use.…”

Section: Introductionmentioning

confidence: 99%

Discrete memory impairments in largely pure chronic users of MDMA

Wunderli

Vonmoos

Fürst

et al. 2017

European Neuropsychopharmacology

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Abbreviated running title:Discrete memory impairments in pure users of MDMA Original Article Submitted:Number of words in the abstract: 241/250 Number of words in the main text: 4493/5000 Number of Tables: 3 Number of Figures: AbstractChronic use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has repeatedly been associated with deficits in working memory, declarative memory, and executive functions. However, previous findings regarding working memory and executive function are inconclusive yet, as in most studies concomitant stimulant use, which is known to affect these functions, was not adequately controlled for. Therefore, we compared the cognitive performance of 26 stimulant-free and largely pure (primary) MDMA users, 25 stimulant-using polydrug MDMA users, and 56 MDMA/stimulantnaïve controls by applying a comprehensive neuropsychological test battery. Neuropsychological tests were grouped into four cognitive domains. Recent drug use was objectively quantified by 6-month hair analyses on 17 substances and metabolites. Considerably lower mean hair concentrations of stimulants (amphetamine, methamphetamine, methylphenidate, cocaine), opioids (morphine, methadone, codeine), and hallucinogens (ketamine, 2C-B) were detected in primary compared to polydrug users, while both user groups did not differ in their MDMA hair concentration. Cohen's d effect sizes for both comparisons, i.e., primary MDMA users vs. controls and polydrug MDMA users vs. controls, were highest for declarative memory (dprimary=.90, dpolydrug=1.21), followed by working memory (dprimary=.52, dpolydrug=.96), executive functions (dprimary=.46, dpolydrug=.86), and attention (dprimary=.23, dpolydrug=.70). Thus, primary MDMA users showed strong and relatively discrete declarative memory impairments, whereas MDMA polydrug users displayed broad and unspecific cognitive impairments. Consequently, even largely pure chronic MDMA use is associated with decreased performance in declarative memory, while additional deficits in working memory and executive functions displayed by polydrug MDMA users are likely driven by stimulant co-use.

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Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research

Abstract: The damaging effects of Ecstasy/MDMA are far more widespread than was realized a few years ago, with new neuropsychobiological deficits still emerging.

Cited by 163 publications

References 151 publications

Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction

Discrete memory impairments in largely pure chronic users of MDMA

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