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Official websites use. Share sensitive information only on official, secure websites. MDMA provides an immediate enjoyable feeling by stimulating the release of neurotransmitters, such as dopamine and serotonin in the brain. Unfortunately, abnormal regulation of the brain neurotransmitters, as well as the increased oxidative stress causes damage to the brain neurons after the MDMA exposure. Only a few studies have been done regarding its treatment. Thus, the treatment of MDMA complications should be further explored mainly by targeting its mechanism of action in the neurotransmitter systems. Hence, this study presents a short review regarding the recent findings on the role of neurotransmitters to cause MDMA neurotoxicity. The results will be useful for future research in elucidating the potential treatment based on the targeted mechanisms to treat the neurotoxic effects of MDMA. Hence, the choices of treatment for MDMA abusers who suffer from the symptoms need to be explored to reduce the effects. Unfortunately, the mechanism of action on how MDMA affects the body and brain needs to be studied first before the best treatment could be applied. MDMA administration was reported previously to cause the excessive release of both hippocampal glutamate and 5-HT concentrations mediated by the activations of NMDA receptors and 5-HT receptors, which damage the neurons in the brain. MDMA also affects memory and learning due to the disruption of hippocampal function, mainly through the alterations in dopaminergic and NMDA receptors. Several treatments have been proposed for MDMA neurotoxicity, such as the manipulation of the reward pathway, protecting the neurons, and regulating the normal level of 5-HT. The amphetamine-type stimulant drugs, such as MDMA or ecstasy become the choice of drug abuse among young people and adults besides opioids, which is due to a feeling of excitement experienced immediately after the administration. The MDMA side effects mostly affect the brain and behavior even after long periods of abstinence. People who want to quit the drug usually fail because of withdrawal complications. Moreover, other complications, such as the lower performance of the learning and memory and also anxiety could disturb their everyday life. Accordingly, this study reviewed the neurotoxic effects of MDMA on neuronal brain activity and MDMA targets, such as receptors and neurotransmitter systems that alter the brain and body functions. Therefore, researchers may target these areas as treatment options. The new findings are always welcomed for the sake of people and the community, especially in addiction. Substance abuse remains a worldwide issue. Data reported by the United Nations on Drugs and Crime on the total number of drug addicts worldwide shows the increasing number of drug users every year. Global trends in the estimated number of drug users 15—64 years old increased from million to million people from to , while people with drug user disorders increased from 26 million to Along with the challenges caused by opiates, the increasing number of amphetamine-type stimulants ATS users and related disorders are unnoticed, especially for MDMA. MDMA has been declared as an illegal substance in most countries. Some countries, such as Norway, Germany, and Canada have classified it as Schedule I drugs, which is illegal to buy or possess without a license. Considering a new trend in the substance abuse preference, the MDMA effects will be reviewed focusing on neurotoxicity and neurodegeneration. Besides, the targeted mechanism for the treatment of MDMA complications will be discussed. Current understanding of the MDMA mechanism of action arises from its effects on the psychological changes and dependence. Psychological changes are explained as the euphoria, sharpened sensory perception, an increase in social performance and empathy, and greater tolerance of the feelings Kalant, The biological mechanisms involved in MDMA exposure are the changes in the serotonergic system, which affects serotonin 5-hydroxytryptamine 5HT and dopamine. Interestingly, a study by Popova et al. Thus, there is still limited knowledge about MDMA mechanisms. Therefore, more extensive studies are needed in order to reveal strong evidence about the exact mechanism of MDMA toxicities. The activation of these receptors triggers a massive release of neurotransmitters. MDMA also inhibits serotonin reuptake by its binding to the transporter protein, thus prolonging signaling at the synapses. This causes the accumulation of the neurotransmitters between the synapses, which can result in excitotoxicity. Although MDMA was reported to improve the emotional and personality problems in psychotherapy as mentioned earlier, its long-term effects can be more adverse. The massive release of serotonin that initially causes the psychotic symptoms can also give rise to the chemical damage to serotonin-releasing cells Kalant, Due to the disruption of the normal brain biological system, MDMA can cause damage to the brain structure and nervous system, which increases the loss of neurons and alters the brain functions. Therefore, three main issues, including neuronal damage, alterations in neurotransmitters, and memory impairments will be reviewed in this present article based on the recent studies on the effects of MDMA abuse. Neuronal damage is the loss of brain cells either because of the alterations by toxic substances or certain diseases. Neuronal cell death can occur due to the increased production of free radicals by neurotoxins. Memory and learning impairment by MDMA also results from the neuronal damages and dysfunction of the nervous system. MDMA administration was studied to cause neurodegeneration by enhancing the release of free radicals. The free radicals, such as reactive oxygen generation inhibit the activity of mitochondrial complex I Karuppagounder et al. The inhibition of mitochondria causes the loss of energy, and consequently neuronal death. Besides, the excessive levels of autophagy are also contributed to the neuronal damage induced by MDMA, which was studied in cultured cortical neurons Li et al. Moreover, as mentioned previously, MDMA is a drug with a binding affinity for the specific serotonin receptors. A study by Collins et al. The loss of parvalbumin neurons in the brain upon MDMA exposure was supported by another study by Anneken et al. It can be generally concluded that the excitation of both hippocampal glutamate and 5-HT concentrations mediated by the activation of NMDA and 5-HT receptors can cause neuronal damage. The deficiency of serotonin transporter also modulated MDMA-mediated neurotoxicity in rats Lizarraga et al. However, some researchers have suggested that MDMA may be able to cause a long-term 5-HT down-regulation without causing structural damage to serotonin neurons Kish, MDMA-induced serotonin deficit has been interpreted as neurotoxicity. However, in a clinical study, the brain imaging studies on MDMA users had been drug-free for 20 weeks or longer have not revealed less serotonin transporter binding levels in the brain Buchert et al. Brain imaging studies on humans have provided evidence regarding the altered serotonergic functioning in recreational ecstasy users. Breivik et al. Tao et al. A recent finding by Mercer et al. A study by Costa et al. Hence, MDMA causes neurotoxicity through different mechanisms; either by acting directly on the neuronal brain activity or by other indirect pathways. Future studies regarding the treatment of the detrimental effects caused by MDMA should focus on the compounds that have the healing properties towards the abnormal neurotransmitter regulations and the damaged neurons. It has been discovered that MDMA impairs learning and memory. A clinical study showed that MDMA users displayed relatively discrete declarative memory impairments, which were quantified by hair analysis for six months, and the pure chronic MDMA use was found to be associated with decreased performance in declarative memory Wunderli et al. The impairment of memory by MDMA was also studied in vivo. Memory deficit was detected in young mice exposed to MDMA that was explained by the increased expression of early markers of plasticity, observed through the reduction in dopaminergic markers in the substantia nigra. MDMA-treated rats also displayed a deficit in recognition memory in the novel recognition test, which was believed to occur due to the damage to dopamine neurons Cadoni et al. Thus, the main focus of the researchers for future studies should be on the treatment through these targeted areas. The toxicity effects induced by MDMA made the researchers motivated to explore its potential treatments. Several therapeutic methods have been suggested by the researchers for the treatment of MDMA abuse. For example, Garcia-Pardo et al. In addition, the potential treatments to protect toxicity caused by MDMA have also been studied. Dextrorphan was believed to prevent the effects of serotonin depletion by MDMA in the striatum, hippocampus, and cortex Finnegan et al. However, the ketoprofen, unfortunately, did not prevent the 5-HT depletion in the hippocampus Anneken et al. Another natural substance was shown to prevent apoptosis induced by MDMA. Ginger was proven to reduce the activation of the caspase cascade responsible for cell death Asl et al. Most of the recent studies and suggestions regarding the targeted treatment for MDMA abuse have focused on attenuating the neurotoxicity and neurotransmitters excitotoxicity in the brain. In future studies, the potential therapeutic substances, either synthetic or natural that can attenuate the long-term effects of MDMA through those involved mechanisms should be highly considered. In summary, people, especially young people, choose MDMA as their drug of choice due to its stimulating effects. The increased energy for doing their basic life activities makes MDMA as a drug of choice. However, these effects are satisfactorily detrimental to our body systems, particularly neuronal cells. As a library, NLM provides access to scientific literature. Basic Clin Neurosci. Find articles by Nor Suliana Mustafa. Nor Hidayah Abu Bakar 1. Find articles by Nor Hidayah Abu Bakar. Nasir Mohamad 1. Find articles by Nasir Mohamad. Liyana Hazwani Mohd Adnan 1. Find articles by Liyana Hazwani Mohd Adnan. Nurul Farah Aina Md Fauzi 1. Abdulsoma Thoarlim 1. Find articles by Abdulsoma Thoarlim. Syed Hadzrullathfi Syed Omar 1. Find articles by Syed Hadzrullathfi Syed Omar. Mohd Shafiee Hamzah 2. Find articles by Mohd Shafiee Hamzah. Zawawi Yusoff 2. Find articles by Zawawi Yusoff. Mahdi Jufri 5. Faculty of Pharmacy, University of Indonesia, Indonesia. Find articles by Mahdi Jufri. Rashidi Ahmad 6. Find articles by Rashidi Ahmad. Conflict of interest The authors declared no conflict of interest. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

Kuala Terengganu buying Ecstasy