In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin2A Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) and Hallucinogen Users

Erritzoe, David; Frøkjær, Vibe G.; Holst, Klaus K.; Christoffersen, M.V.; Johansen, Sys Stybe; Svarer, Claus; Madsen, Jacob; Rasmussen, Peter Mondrup; Ramsøy, Thomas Z.; Jernigan, Terry L.; Knudsen, Gitte M.

doi:10.1001/archgenpsychiatry.2011.56

Cited by 76 publications

(79 citation statements)

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“…More recently, PET studies have reported 5-HT 2A receptor upregulation after chronic MDMA use over broad areas of the cerebral cortex, including: occipital parietal, frontal and frontoparietal regions (Di Iorio et al, 2012) and the dorsolateral prefrontal cortex (DLPFC) and parietal cortex (Urban et al, 2012), which is thought to be due to a loss or reduction in presynaptic signalling. Furthermore, McCann et al (2008), Kish et al (2010) and Erritzoe et al (2011) found reduced SERT binding in abstinent users after recreational use, which is interpreted as compensatory down-regulation. A complicating factor emerges in research in recreational ecstasy users as the majority of individuals who report recreational use of ecstasy use a range of other drugs in addition to ecstasy (Fox et al, 2001;Parrott et al, 2008;Roberts et al, 2013Roberts et al, , 2014 however, in most cases, they report that ecstasy is their "drug of choice".…”

Section: Introductionmentioning

confidence: 99%

Cortical oxygenation suggests increased effort during cognitive inhibition in ecstasy polydrug users

Roberts

Montgomery

2015

J Psychopharmacol

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Background: 3,4-methylenedioxymethamphetamine (ecstasy) is understood to cause serotonin dysfunction and deficits in executive functioning. When investigating executive function, functional neuroimaging allows the physiological changes underlying these deficits to be investigated. The present study investigated behavioural and brain indices of inhibition in ecstasy-polydrug users. Methods: Twenty ecstasy-polydrug users and 20 drug-naïve participants completed an inhibitory control task (Random Letter Generation-RLG) while prefrontal haemodynamic response was assessed using functional Near Infrared Spectroscopy (fNIRS). Results: There were no group differences on background measures including sleep quality and mood state. There were also no behavioural differences between the two groups.However, ecstasy-polydrug users displayed significant increases in oxy-Hb from baseline compared to controls at several voxels relating to areas of the inferior right medial prefrontal cortex, as well the right and left dorsolateral prefrontal cortex. Regression analysis revealed that recency of ecstasy use was a significant predictor of oxy-Hb increase at two voxels over the right hemisphere after controlling for alcohol and cannabis use indices. Conclusion:Ecstasy-polydrug users show increased neuronal activation in the PFC compared to nonusers. This is taken to be compensatory activation/recruitment of additional resources to attain similar performance levels on the task, which may be reversible with prolonged abstinence. FUNDING:This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Section: Introductionmentioning

confidence: 99%

Cortical oxygenation suggests increased effort during cognitive inhibition in ecstasy polydrug users

Roberts

Montgomery

2015

J Psychopharmacol

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“…Regression analysis was used to investigate possible correlations between reaction times (RT) and log 2 to the lifetime intake of ecstasy tablets or log 2 to the number of days since the last use of ecstasy. Due to our previous findings that the effects of cumulative ecstasy lifetime intake and time since last use of ecstasy on SERT binding follow a log 2 at UNIV CALIFORNIA SAN DIEGO on October 14, 2016 jop.sagepub.com Downloaded from distribution, we expected a log 2 -linear relationship between RT and lifetime intake and time since last use (for calculation of number of ecstasy tablets, please see Erritzoe et al, 2011). Analysis and results that include lifetime intake and/or number of days since last use of ecstasy (and the same is the case for amphetamine) will in this manuscript refer to "log 2 to" the number of accumulated lifetime doses/time since last use, but in order to improve readability, in the Results and Discussion sections, we have left out "log 2 to" from the text.…”

Section: Participantsmentioning

confidence: 99%

“…The degree of serotonin depletion as reflected by cerebral SERT binding was assessed with PET and the selective SERT radioligand, 11C-DASB, as described in more detail by Erritzoe et al (2011). In short, PET data were acquired on a GE-Advance scanner (GE, Milwaukee, WI) as a dynamic 90-minute emission recording after intravenous injection of the radiotracer, 11C-DASB.…”

Section: Mdma Use and Sert Bindingmentioning

confidence: 99%

“…Importantly, lowering brain serotonin levels in preclinical models leads to low SERT combined with high serotonin 2A receptor levels, and low SERT has also been found to be associated with high serotonin 2A receptor levels in humans (Erritzoe et al, 2010). The reduction in subcortical SERT binding in ecstasy users seems to be reversible, since a positive correlation with time of abstinence from ecstasy intake has been observed (Buchert et al, 2004;Erritzoe et al, 2011;McCann et al, 2005;Semple et al, 1999). Taken together, data from these preclinical and clinical studies indicate that there is a causal relationship between ecstasy intake and effects on the serotonergic system.…”

Section: Introductionmentioning

confidence: 99%

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Serotonergic neurotransmission in emotional processing: New evidence from long-term recreational poly-drug ecstasy use

et al. 2016

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The brain’s serotonergic system plays a crucial role in the processing of emotional stimuli, and several studies have shown that a reduced serotonergic neurotransmission is associated with an increase in amygdala activity during emotional face processing. Prolonged recreational use of ecstasy (3,4-methylene-dioxymethamphetamine [MDMA]) induces alterations in serotonergic neurotransmission that are comparable to those observed in a depleted state. In this functional magnetic resonance imaging (fMRI) study, we investigated the responsiveness of the amygdala to emotional face stimuli in recreational ecstasy users as a model of long-term serotonin depletion. Fourteen ecstasy users and 12 non-using controls underwent fMRI to measure the regional neural activity elicited in the amygdala by male or female faces expressing anger, disgust, fear, sadness, or no emotion. During fMRI, participants made a sex judgement on each face stimulus. Positron emission tomography with 11C-DASB was additionally performed to assess serotonin transporter (SERT) binding in the brain. In the ecstasy users, SERT binding correlated negatively with amygdala activity, and accumulated lifetime intake of ecstasy tablets was associated with an increase in amygdala activity during angry face processing. Conversely, time since the last ecstasy intake was associated with a trend toward a decrease in amygdala activity during angry and sad face processing. These results indicate that the effects of long-term serotonin depletion resulting from ecstasy use are dose-dependent, affecting the functional neural basis of emotional face processing.

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“…Also, serotonergic (Erritzoe et al, 2011;Reneman et al, 2002) and cognitive (Adamaszek et al, 2010;Nulsen et al, 2010;Parrott et al, 1998;Quednow et al, 2006) deficits have been reported in human chronic MDMA users, which could be due to neurotoxicity or to drug-induced long-lasting regulatory changes (Biezonski and Meyer., 2011).…”

Section: Introductionmentioning

confidence: 99%

3,4-Methylenedioxy-methamphetamine induces in vivo regional up-regulation of central nicotinic receptors in rats and potentiates the regulatory effects of nicotine on these receptors

Piccoli¹,

García-Ratés²,

Camarasa³

et al. 2013

NeuroToxicology

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NIC+MDMA but not when they were given alone. In the hippocampus, MDMA potentiated the α7 regulatory effects of NIC (raising a 25.5% increase to 52.5%) but alone was devoid of effect. MDMA had no effect on heteromeric nAChR in striatum and a coronal section of the midbrain containing superior colliculli, geniculate nuclei, substantia nigra and ventral tegmental area. Specific immunoprecipitation of solubilised receptors suggests that the up-regulated heteromeric nAChRs contain α4 and β2 subunits. Western blots with specific α4 and α7 antibodies showed no significant differences between the groups, indicating that, as reported for nicotine, up-regulation caused by MDMA is due to post-translational events rather than increased receptor synthesis.

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In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin2A Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) and Hallucinogen Users

Cited by 76 publications

References 83 publications

Cortical oxygenation suggests increased effort during cognitive inhibition in ecstasy polydrug users

Cortical oxygenation suggests increased effort during cognitive inhibition in ecstasy polydrug users

Serotonergic neurotransmission in emotional processing: New evidence from long-term recreational poly-drug ecstasy use

3,4-Methylenedioxy-methamphetamine induces in vivo regional up-regulation of central nicotinic receptors in rats and potentiates the regulatory effects of nicotine on these receptors

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