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==Side effects== ===Short-term=== Acute adverse effects are usually the result of high or multiple doses, although single dose toxicity can occur in susceptible individuals.<ref name="Current2013" /> The most serious short-term physical health risks of MDMA are [[hyperthermia]] and [[dehydration]].<ref name="Acute amph toxicity" /><ref name="Hyponatremia" /> Cases of life-threatening or fatal [[hyponatremia]] (excessively low sodium concentration in the blood) have developed in MDMA users attempting to prevent dehydration by [[water intoxication|consuming excessive amounts of water]] without replenishing [[electrolytes]].<ref name="Acute amph toxicity" /><ref name="Hyponatremia" /><ref name="hyperpyrexia">{{cite journal | vauthors = White CM | title = How MDMA's pharmacology and pharmacokinetics drive desired effects and harms | journal = Journal of Clinical Pharmacology | volume = 54 | issue = 3 | pages = 245–52 | date = March 2014 | pmid = 24431106 | doi = 10.1002/jcph.266 | s2cid = 6223741 }}</ref> The immediate adverse effects of MDMA use can include: {{div col|colwidth=27em}} * [[Bruxism]] (grinding and clenching of the teeth)<ref name=Betzler2017/><ref name="pmid22392347" /><ref name=Current2013 /> * [[Dehydration]]<ref name="pmid22392347"/><ref name="Acute amph toxicity" /><ref name="Hyponatremia" /> * [[Diarrhea]]<ref name="Acute amph toxicity" /> * [[Erectile dysfunction]]<ref name=Betzler2017/><ref>{{cite journal | vauthors = Spauwen LW, Niekamp AM, Hoebe CJ, Dukers-Muijrers NH | title = Drug use, sexual risk behaviour and sexually transmitted infections among swingers: a cross-sectional study in The Netherlands | journal = Sexually Transmitted Infections | volume = 91 | issue = 1 | pages = 31–6 | date = February 2015 | pmid = 25342812 | doi = 10.1136/sextrans-2014-051626 | quote = It is known that some recreational drugs (eg, MDMA or GHB) may hamper the potential to ejaculate or maintain an erection. | doi-access = free }}</ref> * [[Hyperthermia]]<ref name=Betzler2017/><ref name="pmid22392347" /><ref name="Hyponatremia" /> * Increased wakefulness or [[insomnia]]<ref name=Betzler2017/><ref name="Acute amph toxicity" /> * Increased perspiration and sweating<ref name="Acute amph toxicity" /><ref name="Hyponatremia" /> * Increased [[heart rate]] and [[blood pressure]]<ref name=Betzler2017/><ref name="pmid22392347" /><ref name="Hyponatremia" /> * Increased [[Psychomotor agitation|psychomotor]] activity<ref name=Betzler2017/> * Loss of [[appetite]]<ref name=Betzler2017/><ref name="Toxnet MDMA after-effects"/> * Nausea and vomiting<ref name=Current2013 /> * Visual and auditory hallucinations (rarely)<ref name=Betzler2017/> {{div col end}} Other adverse effects that may occur or persist for up to a week following cessation of moderate MDMA use include:<ref name="Toxnet MDMA after-effects" /><ref name=Current2013 /> ; Physiological {{div col|colwidth=18em}} * Insomnia<ref name="Toxnet MDMA after-effects" /> * Loss of appetite<ref name="Toxnet MDMA after-effects" /> * Tiredness or lethargy<ref>{{Cite web|url=http://emedicine.medscape.com/article/821572-overview#showall|title=MDMA Toxicity: Background, Pathophysiology, Epidemiology|vauthors=Hahn IH|date=25 March 2015|website=Medscape|access-date=14 May 2016|archive-date=11 May 2016|archive-url=https://web.archive.org/web/20160511222711/http://emedicine.medscape.com/article/821572-overview#showall|url-status=live}}</ref><ref>{{Cite book|chapter-url=https://books.google.com/books?id=yGeBj9U6Za8C|title=Drug Abuse and Addiction in Medical Illness: Causes, Consequences and Treatment| vauthors = Parrott AC |date=2012|publisher=Springer Science & Business Media|isbn=978-1-4614-3375-0| veditors = Verster J, Brady K, Galanter M, Conrod P |page=179|chapter=13. MDMA and LSD }}</ref> * [[Trismus]] (lockjaw)<ref name="Current2013" /> {{div col end}} ;Psychological {{div col|colwidth=18em}} * [[Anhedonia]]<ref name="Toxnet MDMA after-effects" /> * Anxiety or paranoia<ref name="Toxnet MDMA after-effects"/> * Depression<ref name="Toxnet MDMA after-effects" /><ref name="Current2013" /> * Impulsiveness<ref name="Toxnet MDMA after-effects" /> * Irritability<ref name="Toxnet MDMA after-effects" /> * Memory impairment<ref name="Current2013" /> * Restlessness<ref name="Toxnet MDMA after-effects" /> {{div col end}} ===Long-term=== {{As of|2015}}, the long-term effects of MDMA on human brain structure and function have not been fully determined.<ref name="Abstinent MDMA fMRI review">{{cite journal | vauthors = Garg A, Kapoor S, Goel M, Chopra S, Chopra M, Kapoor A, McCann UD, Behera C | title = Functional Magnetic Resonance Imaging in Abstinent MDMA Users: A Review | journal = Current Drug Abuse Reviews | volume = 8 | issue = 1 | pages = 15–25 | date = 2015 | pmid = 25731754 | doi = 10.2174/1874473708666150303115833 }}</ref> However, there is consistent evidence of structural and functional deficits in MDMA users with high lifetime exposure.<ref name="Abstinent MDMA fMRI review" /> These structural or functional changes appear to be dose dependent and may be less prominent in MDMA users with only a moderate (typically <50 doses used and <100 tablets consumed) lifetime exposure. Nonetheless, moderate MDMA use may still be [[Neurotoxicity|neurotoxic]] and what constitutes moderate use is not clearly established.<ref name="mueller2015">{{cite journal | vauthors = Mueller F, Lenz C, Steiner M, Dolder PC, Walter M, Lang UE, Liechti ME, Borgwardt S | title = Neuroimaging in moderate MDMA use: A systematic review | journal = Neuroscience and Biobehavioral Reviews | volume = 62 | pages = 21–34 | date = March 2016 | pmid = 26746590 | doi = 10.1016/j.neubiorev.2015.12.010 | doi-access = free }}</ref> Furthermore, it is not clear yet whether "typical" recreational users of MDMA (1 to 2 pills of 75 to 125{{nbsp}}mg MDMA or analogue every 1 to 4 weeks) will develop neurotoxic brain lesions.<ref>{{cite journal | vauthors = Gouzoulis-Mayfrank E, Daumann J | title = Neurotoxicity of drugs of abuse--the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines | journal = Dialogues in Clinical Neuroscience | volume = 11 | issue = 3 | pages = 305–17 | date = 2009 | doi = 10.31887/DCNS.2009.11.3/egmayfrank | pmid = 19877498 | pmc = 3181923 }}</ref> Long-term exposure to MDMA in humans has been shown to produce marked [[neurodegeneration]] in [[striatal]], [[hippocampal]], [[prefrontal cortex|prefrontal]], and [[occipital cortex|occipital]] serotonergic [[axon terminal]]s.<ref name="Abstinent MDMA fMRI review" /><ref name="Meth MDMA NTox">{{cite journal | vauthors = Halpin LE, Collins SA, Yamamoto BK | title = Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine | journal = Life Sciences | volume = 97 | issue = 1 | pages = 37–44 | date = February 2014 | pmid = 23892199 | pmc = 3870191 | doi = 10.1016/j.lfs.2013.07.014 | quote = In contrast, MDMA produces damage to serotonergic, but not dopaminergic axon terminals in the striatum, hippocampus, and prefrontal cortex (Battaglia et al., 1987, O'Hearn et al., 1988). The damage associated with Meth and MDMA has been shown to persist for at least 2 years in rodents, non-human primates and humans (Seiden et al., 1988, Woolverton et al., 1989, McCann et al., 1998, Volkow et al., 2001a, McCann et al., 2005) }}</ref> Neurotoxic damage to serotonergic axon terminals has been shown to persist for more than two years.<ref name="Meth MDMA NTox" /> Elevations in brain temperature from MDMA use are positively correlated with MDMA-induced neurotoxicity.<ref name="pmid22392347" /><ref name="Abstinent MDMA fMRI review" /><ref name="mueller2015" /> However, most studies on MDMA and serotonergic neurotoxicity in humans focus more on heavy users who consume as much as seven times or more the amount that most users report taking. The evidence for the presence of serotonergic neurotoxicity in casual users who take lower doses less frequently is not conclusive.<ref>{{cite journal | vauthors = Szigeti B, Winstock AR, Erritzoe D, Maier LJ | title = Are ecstasy induced serotonergic alterations overestimated for the majority of users? | journal = Journal of Psychopharmacology | volume = 32 | issue = 7 | pages = 741–748 | date = July 2018 | pmid = 29733742 | doi = 10.1177/0269881118767646 | s2cid = 13660975 | quote = Given the dose-response relationship between MDMA exposure and SERT reductions and the statistically non-significant SERT binding differences for users with use levels similar to the majority of real-life users, it can be speculated that SERT levels may not be significantly affected for most recreational ecstasy users. }}</ref> However, adverse [[neuroplastic]] changes to brain [[microvasculature]] and [[white matter]] have been observed to occur in humans using low doses of MDMA.<ref name="pmid22392347" /><ref name="Abstinent MDMA fMRI review" /> Reduced [[gray matter]] density in certain brain structures has also been noted in human MDMA users.<ref name="pmid22392347" /><ref name="Abstinent MDMA fMRI review" /> Global reductions in gray matter volume, thinning of the parietal and orbitofrontal cortices, and decreased hippocampal activity have been observed in long term users.<ref name="Betzler2017" /> The effects established so far for recreational use of ecstasy lie in the range of moderate to severe effects for [[serotonin transporter]] reduction.<ref>{{cite journal | vauthors = Roberts CA, Jones A, Montgomery C | title = Meta-analysis of molecular imaging of serotonin transporters in ecstasy/polydrug users | journal = Neuroscience and Biobehavioral Reviews | volume = 63 | pages = 158–67 | date = April 2016 | pmid = 26855234 | doi = 10.1016/j.neubiorev.2016.02.003 | doi-access = free }}</ref> Impairments in multiple aspects of cognition, including attention, learning, memory, [[Role of serotonin in visual orientation processing#MDMA and Visual Orientation Processing|visual processing]], and sleep, have been found in regular MDMA users.<ref name=Betzler2017/><ref name=Current2013 /><ref name=Pharm2014>{{cite journal | vauthors = Parrott AC | title = The potential dangers of using MDMA for psychotherapy | journal = Journal of Psychoactive Drugs | volume = 46 | issue = 1 | pages = 37–43 | year = 2014 | pmid = 24830184 | doi = 10.1080/02791072.2014.873690 | s2cid = 23485480 | url = https://www.researchgate.net/publication/262381558 }}</ref><ref name="Abstinent MDMA fMRI review" /> The magnitude of these impairments is correlated with lifetime MDMA usage<ref name=Current2013 /><ref name=Pharm2014 /><ref name="Abstinent MDMA fMRI review" /> and are partially reversible with abstinence.<ref name=Betzler2017/> Several forms of memory are impaired by chronic ecstasy use;<ref name=Current2013 /><ref name=Pharm2014 /> however, the effects for memory impairments in ecstasy users are generally small overall.<ref>{{cite journal|vauthors=Rogers G, Elston J, Garside R, Roome C, Taylor R, Younger P, Zawada A, Somerville M|date=January 2009|title=The harmful health effects of recreational ecstasy: a systematic review of observational evidence|journal=[[Health Technology Assessment (journal)|Health Technology Assessment]]|volume=13|issue=6|pages=iii–iv, ix–xii, 1–315|doi=10.3310/hta13050|pmid=19195429|doi-access=free|hdl=10871/11534|hdl-access=free}}</ref><ref name="Meta analysis - MDMA memory impairment">{{cite journal | vauthors = Kuypers KP, Theunissen EL, van Wel JH, de Sousa Fernandes Perna EB, Linssen A, Sambeth A, Schultz BG, Ramaekers JG | title = Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective | journal = PLOS ONE | volume = 11 | issue = 2 | pages = e0149438 | year = 2016 | pmid = 26907605 | pmc = 4764468 | doi = 10.1371/journal.pone.0149438 | bibcode = 2016PLoSO..1149438K | doi-access = free }}</ref> MDMA use is also associated with increased impulsivity and depression.<ref name=Betzler2017/> Serotonin depletion following MDMA use can cause depression in subsequent days. In some cases, depressive symptoms persist for longer periods.<ref name=Betzler2017/> Some studies indicate repeated recreational use of ecstasy is associated with depression and anxiety, even after quitting the drug.<ref>{{cite journal | vauthors = Laws KR, Kokkalis J | title = Ecstasy (MDMA) and memory function: a meta-analytic update | journal = Human Psychopharmacology | volume = 22 | issue = 6 | pages = 381–8 | date = August 2007 | pmid = 17621368 | doi = 10.1002/hup.857 | s2cid = 25353240 }}</ref> Depression is one of the main reasons for cessation of use.<ref name=Betzler2017/> At high doses, MDMA induces a [[neuroimmune system|neuroimmune response]] that, through several mechanisms, increases the permeability of the [[blood–brain barrier]], thereby making the brain more susceptible to environmental toxins and [[pathogen]]s.<ref name="MDMA BBB">{{cite journal | vauthors = Kousik SM, Napier TC, Carvey PM | title = The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation | journal = Frontiers in Pharmacology | volume = 3 | pages = 121 | year = 2012 | pmid = 22754527 | pmc = 3386512 | doi = 10.3389/fphar.2012.00121 | doi-access = free }}</ref><ref>{{cite book| vauthors = McMillan B, Starr C |title=Human biology |date=2014 |publisher=Brooks/Cole Cengage Learning |location=Belmont, CA |isbn=978-1-133-59916-6 |edition=10th }}</ref>{{Page needed|date=September 2015}} In addition, MDMA has [[immunosuppressive]] effects in the [[peripheral nervous system]] and pro-inflammatory effects in the [[central nervous system]].<ref>{{cite journal | vauthors = Boyle NT, Connor TJ | title = Methylenedioxymethamphetamine ('Ecstasy')-induced immunosuppression: a cause for concern? | journal = British Journal of Pharmacology | volume = 161 | issue = 1 | pages = 17–32 | date = September 2010 | pmid = 20718737 | pmc = 2962814 | doi = 10.1111/J.1476-5381.2010.00899.X }}</ref> MDMA may increase the risk of [[cardiac valvulopathy]] in heavy or long-term users due to activation of serotonin [[5-HT2B receptor|5-HT<sub>2B</sub> receptor]]s.<ref name="pmid24361689">{{cite journal | vauthors = Cavero I, Guillon JM | title = Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy | journal = Journal of Pharmacological and Toxicological Methods | volume = 69 | issue = 2 | pages = 150–161 | date = 2014 | pmid = 24361689 | doi = 10.1016/j.vascn.2013.12.004 }}</ref><ref name="pmid28676029">{{cite journal | vauthors = Padhariya K, Bhandare R, Canney D, Velingkar V | title = Cardiovascular Concern of 5-HT2B Receptor and Recent Vistas in the Development of Its Antagonists | journal = Cardiovascular & Hematological Disorders Drug Targets | volume = 17 | issue = 2 | pages = 86–104 | date = 2017 | pmid = 28676029 | doi = 10.2174/1871529X17666170703115111 }}</ref> MDMA induces cardiac [[epigenetics|epigenetic changes]] in [[DNA methylation]], particularly hypermethylation changes.<ref>{{cite journal | vauthors = Koczor CA, Ludlow I, Hight RS, Jiao Z, Fields E, Ludaway T, Russ R, Torres RA, Lewis W | title = Ecstasy (MDMA) Alters Cardiac Gene Expression and DNA Methylation: Implications for Circadian Rhythm Dysfunction in the Heart | journal = Toxicological Sciences | volume = 148 | issue = 1 | pages = 183–191 | date = November 2015 | pmid = 26251327 | pmc = 4731408 | doi = 10.1093/toxsci/kfv170 }}</ref> ===Reinforcement disorders=== <!--Dependence--> Approximately 60% of MDMA users experience [[drug withdrawal|withdrawal]] symptoms when they stop taking MDMA.<ref name="Toxnet MDMA after-effects"/> Some of these symptoms include fatigue, loss of appetite, depression, and trouble concentrating.<ref name="Toxnet MDMA after-effects"/> [[Drug tolerance|Tolerance]] to some of the desired<!-- (e.g., euphoria) - need ref--> and adverse<!-- (e.g., loss of appetite) - need ref--> effects of MDMA is expected to occur with consistent MDMA use.<ref name="Toxnet MDMA after-effects"/> A 2007 [[Delphi method|delphic analysis]] of a panel of experts in pharmacology, psychiatry, law, policing and others estimated MDMA to have a psychological dependence and physical dependence potential roughly three-fourths to four-fifths that of cannabis.<ref name="pmid17382831">{{cite journal |vauthors=Nutt D, King LA, Saulsbury W, Blakemore C |title=Development of a rational scale to assess the harm of drugs of potential misuse |journal=Lancet |volume=369 |issue=9566 |pages=1047–1053 |date=March 2007 |pmid=17382831 |doi=10.1016/S0140-6736(07)60464-4 |s2cid=5903121 |author-link1=David Nutt |author-link4=Colin Blakemore}}<br />Lay summary: {{cite web |date=23 March 2007 |title=Scientists want new drug rankings |website=BBC News |url=http://news.bbc.co.uk/2/hi/health/6474053.stm |access-date=4 April 2008 |archive-date=2 December 2007 |archive-url=https://web.archive.org/web/20071202233524/http://news.bbc.co.uk/2/hi/health/6474053.stm |url-status=live }}</ref> <!--Addiction--> MDMA has been shown to induce [[ΔFosB]] in the [[nucleus accumbens]].<ref name="MDMA ΔFosB">{{cite journal | vauthors = Olausson P, Jentsch JD, Tronson N, Neve RL, Nestler EJ, Taylor JR | title = DeltaFosB in the nucleus accumbens regulates food-reinforced instrumental behavior and motivation | journal = The Journal of Neuroscience | volume = 26 | issue = 36 | pages = 9196–204 | date = September 2006 | pmid = 16957076 | pmc = 6674495 | doi = 10.1523/JNEUROSCI.1124-06.2006 }}</ref> Because MDMA releases dopamine in the [[striatum]], the mechanisms by which it induces ΔFosB in the nucleus accumbens are analogous to other dopaminergic psychostimulants.<ref name="MDMA ΔFosB" /><ref name="Nestler">{{cite journal | vauthors = Robison AJ, Nestler EJ | title = Transcriptional and epigenetic mechanisms of addiction | journal = Nature Reviews. Neuroscience | volume = 12 | issue = 11 | pages = 623–37 | date = October 2011 | pmid = 21989194 | pmc = 3272277 | doi = 10.1038/nrn3111 }}</ref> Therefore, chronic use of MDMA at high doses can result in [[neuroplasticity|altered brain structure]] and [[drug addiction]] that occur as a consequence of ΔFosB overexpression in the nucleus accumbens.<ref name="Nestler" /> MDMA is less addictive than other stimulants such as methamphetamine and cocaine.<ref>{{cite book| vauthors = Mack AH, Brady KT, Miller SI, Frances RJ |title=Clinical Textbook of Addictive Disorders|publisher=Guilford Publications |isbn=978-1-4625-2169-2 |page=169 |url=https://books.google.com/books?id=88W_CwAAQBAJ&pg=PA171 |quote=MDMA's addictive liability appears to be lower than that of other drugs of abuse....|date=2016-05-12}}</ref><ref>{{cite journal | vauthors = Favrod-Coune T, Broers B | title = The Health Effect of Psychostimulants: A Literature Review | journal = Pharmaceuticals | volume = 3 | issue = 7 | pages = 2333–2361 | date = July 2010 | pmid = 27713356 | pmc = 4036656 | doi = 10.3390/ph3072333 | quote = It seems to present a smaller addiction potential than cocaine or methamphetamine. | doi-access = free }}</ref> Compared with amphetamine, MDMA and its metabolite MDA are less reinforcing.<ref>{{cite book |vauthors=Ries R, Miller SC, Fiellin DA |title=Principles of addiction medicine. |date=2009 |publisher=Wolters Kluwer/Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-7477-2 |page=226 |edition=4th |url=https://books.google.com/books?id=j6GGBud8DXcC&pg=PA226 |quote=MDA and MDMA are less reinforcing than amphetamine... |access-date=11 January 2017 |archive-date=13 January 2023 |archive-url=https://web.archive.org/web/20230113000536/https://books.google.com/books?id=j6GGBud8DXcC&pg=PA226 |url-status=live }}</ref> <!--Diagnostic criteria--> One study found approximately 15% of chronic MDMA users met the [[DSM-IV]] diagnostic criteria for [[substance dependence]].<ref name=Steinkellner2011>{{cite journal | vauthors = Steinkellner T, Freissmuth M, Sitte HH, Montgomery T | title = The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine | journal = Biological Chemistry | volume = 392 | issue = 1–2 | pages = 103–15 | date = January 2011 | pmid = 21194370 | pmc = 4497800 | doi = 10.1515/BC.2011.016 | quote = ...approximately 15% of routine MDMA users recently fit the diagnostic criteria for MDMA dependence according to the Diagnostic and Statistical Manual, fourth edition/DSMIV. }}</ref> However, there is little evidence for a specific diagnosable MDMA dependence syndrome because MDMA is typically used relatively infrequently.<ref name=Epstein2013>{{cite book|veditors=McCrady BS, Epstein EE|title=Addictions: a comprehensive guidebook|date=2013|publisher=Oxford University Press|location=Oxford|isbn=978-0-19-975366-6|page=299|edition=Second|url=https://books.google.com/books?id=MUYfAQAAQBAJ&pg=PA299|access-date=11 January 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113000537/https://books.google.com/books?id=MUYfAQAAQBAJ&pg=PA299|url-status=live}}</ref> <!--Treatment--> There are currently no medications to treat MDMA addiction.<ref>{{cite book|vauthors=Mack AH, Brady KT, Miller SI, Frances RJ|title=Clinical Textbook of Addictive Disorders|publisher=Guilford Publications|isbn=978-1-4625-2169-2|page=171|url=https://books.google.com/books?id=88W_CwAAQBAJ&q=mdma+addiction&pg=PA171|quote=There are no known pharmacological treatments for MDMA addiction.|date=2016-05-12|access-date=13 October 2020|archive-date=19 January 2023|archive-url=https://web.archive.org/web/20230119130056/https://books.google.com/books?id=88W_CwAAQBAJ&q=mdma+addiction&pg=PA171|url-status=live}}</ref> ===During pregnancy=== MDMA is a moderately [[teratogenic drug]] (i.e., it is toxic to the fetus).<ref name=vorhees>{{cite journal | vauthors = Vorhees CV | title = Methods for detecting long-term CNS dysfunction after prenatal exposure to neurotoxins | journal = Drug and Chemical Toxicology | volume = 20 | issue = 4 | pages = 387–99 | date = November 1997 | pmid = 9433666 | doi = 10.3109/01480549709003895 }}</ref><ref name=meamar>{{cite journal | vauthors = Meamar R, Karamali F, Sadeghi HM, Etebari M, Nasr-Esfahani MH, Baharvand H | title = Toxicity of ecstasy (MDMA) towards embryonic stem cell-derived cardiac and neural cells | journal = Toxicology in Vitro | volume = 24 | issue = 4 | pages = 1133–8 | date = June 2010 | pmid = 20230888 | doi = 10.1016/j.tiv.2010.03.005 | bibcode = 2010ToxVi..24.1133M | quote = In summary, MDMA is a moderate teratogen that could influence cardiac and neuronal differentiation in the ESC model and these results are in concordance with previous in vivo and in vitro models. }}</ref> [[Uterus|In utero]] exposure to MDMA is associated with a [[neurotoxicity|neuro]]- and [[cardiotoxicity]]<ref name=meamar/> and impaired motor functioning. Motor delays may be temporary during infancy or long-term. The severity of these developmental delays increases with heavier MDMA use.<ref name=Pharm2014 /><ref name=singer>{{cite journal | vauthors = Singer LT, Moore DG, Fulton S, Goodwin J, Turner JJ, Min MO, Parrott AC | title = Neurobehavioral outcomes of infants exposed to MDMA (Ecstasy) and other recreational drugs during pregnancy | journal = Neurotoxicology and Teratology | volume = 34 | issue = 3 | pages = 303–10 | year = 2012 | pmid = 22387807 | pmc = 3367027 | doi = 10.1016/j.ntt.2012.02.001 | bibcode = 2012NTxT...34..303S }}</ref> MDMA has been shown to promote the survival of fetal dopaminergic neurons in culture.<ref>{{cite journal | vauthors = Lipton JW, Tolod EG, Thompson VB, Pei L, Paumier KL, Terpstra BT, Lynch KA, Collier TJ, Sortwell CE | title = 3,4-Methylenedioxy-N-methamphetamine (ecstasy) promotes the survival of fetal dopamine neurons in culture | journal = Neuropharmacology | volume = 55 | issue = 5 | pages = 851–859 | date = October 2008 | pmid = 18655796 | doi = 10.1016/j.neuropharm.2008.06.062 | pmc = 2572681 }}</ref>
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