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3,4-Methylenedioxymethamphetamine (MDMA) and Synaptic Dopamine

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Handbook of Substance Misuse and Addictions

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Abstract

The aim of the present chapter is to shed light on different aspects related to synaptic dopamine and clinical effects of 3,4-methylenedioxymethamphetamine (MDMA). MDMA is a psychoactive stimulant abused by young people worldwide. Numerous studies demonstrated circulating catecholamine concentrations increase after MDMA administration, indicating sympathetic system activation modulating psychomotor and neuroendocrine function.

Its mechanism of action at synaptic terminals of the dopaminergic system is strongly similar to a cocaine-like effect attributable to an inhibition of the plasma membrane transporters for dopamine (DAT) and to an increased extracellular concentration of serotonin (5-HT). Clinical and preclinical studies have investigated the effects of repeated MDMA exposure. It produces neuroadaptive responses at both serotoninergic and dopaminergic level coherently with the development and maintenance of MDMA self-administration in some experimental animals and the development of a substance misuse in some humans. More systematic investigation in humans should be assessed, focusing on interindividual variables in MDMA pharmacokinetics-pharmacodynamics to better understand its acute specific pharmacological effects and toxicity.

Despite its misuse, there is a great enthusiasm from clinicians who see the potential role of MDMA as a powerful addition to psychotherapy for the treatment of post-traumatic stress disorder (PTSD), as well as a potential primary treatment for social dysfunction occurring in a wide range of other neuropsychiatric disorders (social anxiety, autism, schizophrenia, and alcohol use disorders).

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Abbreviations

5-HT:

5-hydroxytryptamine or serotonin

BP:

Blood pressure

CNS:

Central Nervous System

CPP:

Conditioned place preference

CYP2D6:

Cytochrome P450

DA:

Dopamine

DAT:

Dopamine transporter

DhβE:

Dihydroβerythroidine

FDA:

Food and Drug Administration

H:

Histamine

HR:

Heart rate

LSD:

Lysergic Acid Diethylamide

M:

Muscarine

MAO:

Monoamine oxidase

MDA:

3,4-methylenedioxyamphetamine

MDE:

3,4-methylenedioxyethylamphetamine

MDMA:

3,4-methylenedioxymethamphetamine

MLA:

Methyllycaconitine

MMDA:

3-methoxy-4,5-methylenedioxyamphetamine

nAChRs:

Nicotinic receptors

NE:

Norepinephrine

PTSD:

Post-traumatic stress disorder

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SERT:

Serotonin transporter

SNpc:

Substantia Nigra pars compacta

SSRI:

Selective serotonin reuptake inhibitor

T:

Temperature

VMAT:

Vesicular monoamine transporter

VTA:

Ventral Tegmental Area

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Authors and Affiliations

  1. IRCCS Neuromed, Pozzilli, Italy

    Francesca Romana Rizzo & Antonio Bruno

  2. IRCCS Fondazione Santa Lucia, Rome, Italy

    Mauro Federici & Nicola Biagio Mercuri

  3. Department of System Medicine, University of Rome Tor Vergata, Rome, Italy

    Nicola Biagio Mercuri

Authors
  1. Francesca Romana Rizzo
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  2. Antonio Bruno
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  3. Mauro Federici
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  4. Nicola Biagio Mercuri
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Correspondence to Nicola Biagio Mercuri .

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Editors and Affiliations

  1. School of Life Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Victor R. Preedy

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Rizzo, F.R., Bruno, A., Federici, M., Mercuri, N.B. (2022). 3,4-Methylenedioxymethamphetamine (MDMA) and Synaptic Dopamine. In: Patel, V.B., Preedy, V.R. (eds) Handbook of Substance Misuse and Addictions. Springer, Cham. https://doi.org/10.1007/978-3-030-92392-1_116

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