Yosta Vegting1, Liesbeth Reneman2,3, Jan Booij4,3. 1. Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, 1105, AZ, Amsterdam, The Netherlands. y.vegting@amc.uva.nl. 2. Department of Radiology, Academic Medical Center, University of Amsterdam, 1105, AZ, Amsterdam, The Netherlands. 3. Brain Imaging Center, Academic Medical Center, University of Amsterdam, 1105, AZ, Amsterdam, The Netherlands. 4. Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, 1105, AZ, Amsterdam, The Netherlands.
Abstract
RATIONALE: Ecstasy is a commonly used psychoactive drug with 3,4-methylenedioxymethamphetamine (MDMA) as the main content. Importantly, it has been suggested that use of MDMA may be neurotoxic particularly for serotonergic (5-hydroxytryptamine (5-HT)) neurons. In the past decades, several molecular imaging studies examined directly in vivo the effects of ecstasy/MDMA on neurotransmitter systems. OBJECTIVES: The objective of the present study is to review the effects of ecstasy/MDMA on neurotransmitter systems as assessed by molecular imaging studies in small animals, non-human primates and humans. METHODS: A search in PubMed was performed. Eighty-eight articles were found on which inclusion and exclusion criteria were applied. RESULTS: Thirty-three studies met the inclusion criteria; all were focused on the 5-HT or dopamine (DA) system. Importantly, 9 out of 11 of the animal studies that examined the effects of MDMA on 5-HT transporter (SERT) availability showed a significant loss of binding potential. In human studies, this was the case for 14 out of 16 studies, particularly in heavy users. In abstinent users, significant recovery of SERT binding was found over time. Most imaging studies in humans that focused on the DA system did not find any significant effect of ecstasy/MDMA use. CONCLUSIONS: Preclinical and clinical molecular imaging studies on the effects of ecstasy/MDMA use/administration on neurotransmitter systems show quite consistent alterations of the 5-HT system. Particularly, in human studies, loss of SERT binding was observed in heavy ecstasy users, which might reflect 5-HT neurotoxicity, although alternative explanations (e.g. down-regulation of the SERT) cannot be excluded.
RATIONALE: Ecstasy is a commonly used psychoactive drug with 3,4-methylenedioxymethamphetamine (MDMA) as the main content. Importantly, it has been suggested that use of MDMA may be neurotoxic particularly for serotonergic (5-hydroxytryptamine (5-HT)) neurons. In the past decades, several molecular imaging studies examined directly in vivo the effects of ecstasy/MDMA on neurotransmitter systems. OBJECTIVES: The objective of the present study is to review the effects of ecstasy/MDMA on neurotransmitter systems as assessed by molecular imaging studies in small animals, non-human primates and humans. METHODS: A search in PubMed was performed. Eighty-eight articles were found on which inclusion and exclusion criteria were applied. RESULTS: Thirty-three studies met the inclusion criteria; all were focused on the 5-HT or dopamine (DA) system. Importantly, 9 out of 11 of the animal studies that examined the effects of MDMA on 5-HT transporter (SERT) availability showed a significant loss of binding potential. In human studies, this was the case for 14 out of 16 studies, particularly in heavy users. In abstinent users, significant recovery of SERT binding was found over time. Most imaging studies in humans that focused on the DA system did not find any significant effect of ecstasy/MDMA use. CONCLUSIONS: Preclinical and clinical molecular imaging studies on the effects of ecstasy/MDMA use/administration on neurotransmitter systems show quite consistent alterations of the 5-HT system. Particularly, in human studies, loss of SERT binding was observed in heavy ecstasy users, which might reflect 5-HT neurotoxicity, although alternative explanations (e.g. down-regulation of the SERT) cannot be excluded.
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