Functional Magnetic Resonance Imaging in Abstinent MDMA Users: A Review

Abstract

Ecstasy or 3,4-methylenedioxymethamphetamine (MDMA) is a popular drug of abuse. In the animal studies MDMA has been shown to have deleterious effects on the serotonergic neurotransmitter system. Understanding the adverse effects of MDMA on human brain function is of considerable importance owing to the rising number of MDMA users. Various neuroimaging studies have investigated the structural, chemical and functional differences in the brain integrity of chronic MDMA users. Various neurocognitive domains like working memory, episodic memory, semantic memory, visual stimulation, motor function and impulsivity have been compared between chronic MDMA users and nonusers using fMRI. The fMRI studies remain much more sensitive in studying the neurological deficits associated with chronic MDMA use as compared to the cognitive studies alone and therefore they serve as a prelude in our understanding of MDMA induced neurotoxicity. However they still face certain limitations contributing to inconsistency in the results and further research is needed before we can draw definitive conclusions regarding the neurotoxic effects of MDMA.

DARK Classics in Chemical Neuroscience: Aminorex Analogues

“…It has recently been shown that 4,4′-DMAR inhibits the vesicular monoamine transporter 2 (VMAT2; SLC18A2) with a potency similar to that of MDMA . Perturbed function of VMAT2 has been associated with neurotoxicity. , Still, MDMA has been shown to only be neurotoxic when consumed in high doses over a long periods of time. − As mentioned before, in contrast to other amphetamine-type stimulants, 4,4′-DMAR does not interact with rat and mouse TAAR1 and therefore lacks the autoinhibitory pathway that attenuates monoamine release and mediates the neuroprotective effects. , It has however been shown that many psychoactive compounds stimulate human TAAR1 less potently than the receptor’s rodent counterparts . It is currently not confirmed whether aminorex and its derivatives are neurotoxic.…”

Neuroprotective Effects of Carnitine and Its Potential Application to Ameliorate Neurotoxicity

“…MDMA exposure causes increased noradrenaline, serotonin, and dopamine release, and adverse effects such as hyperthermia and dehydration can occur. MDMA is neurotoxic, and repeated use leads to neurodegeneration of axon terminals and structural changes in gray and white matter . Pretreatment of rats with ALC (100 mg/kg, ip) reversed the effects of MDMA exposure.…”

Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine

“…177 In general, neuroimaging studies used to assess the effects of MDMA in humans have produced mixed findings, with no clear evidence that MDMA is safe or neurotoxic. 178,179 Finally, when compared with MDMA-naıve controls, MDMA users are more likely to be afflicted with mental illnesses including depression, psychotic disorders, eating disorders, and anxiety disorders. 180 While retrospective studies on MDMA-using populations are certainly important, there are several confounding factors that limit the interpretability of these data.…”

“…Heavy MDMA users tend to have lower cerebral spinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)the principal metabolite of serotoninand thus, serotonergic toxicity has been presumed . In general, neuroimaging studies used to assess the effects of MDMA in humans have produced mixed findings, with no clear evidence that MDMA is safe or neurotoxic. , Finally, when compared with MDMA-naı̈ve controls, MDMA users are more likely to be afflicted with mental illnesses including depression, psychotic disorders, eating disorders, and anxiety disorders …”