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Strong girl holding a plate behind her backSince the ’90s, popularity of the designer drug Ecstasy (MDMA) has soared, successfully securing a place in almost everyone’s recreational drug vocabulary. Millions of high school and college students worldwide have tried the drug. Much of Ecstasy’s popularity lies in its unique profile; instead of leaving the user stoned or drunk, MDMA can increase clarity of thought while instilling a sense of empathy for others and a positive view of oneself. Sound like the perfect drug? Not quite. Evidence of neurotoxicity is abundant and discourages many users from taking the drug on a regular basis. Because of this, MDMA probably has little relevance to physique enhancement. Nonetheless, it remains a fascinating drug, albeit disguised by myths and propaganda. But as usual, Chemically Correct is here to help astute minds sort out the real data.


Unlike the subjects of my previous articles (bupropion and nicotine), the history of MDMA hasn’t been lost in the nameless world of the pharmaceutical industry, nor does it date back to the beginning of time. David Pearce has compiled an in-depth compilation of MDMA history and pharmacology at, and I’m indebted to him for the brief history (as well as much of the other information) I’m about to provide here. The German pharmaceutical company Merck first synthesized MDMA in the early 1900’s. They created the compound as an intermediate during the synthesis of a vasoconstrictor. The CIA showed a brief interest in MDMA during the 1950s, but it never reached human testing and was quickly abandoned. The true revival of MDMA from pharmaceutical obscurity occurred in the late 1970s when psychedelic chemist Alexander Shulgin not only synthesized MDMA, but tried it as well. His account of his synthesis and experience with MDMA (as well as many of his other creations) can be found in his book, PiHKAL (Phenylethylamines I Have Known and Loved). He wrote of his experience, “I have never felt so great, or believed this to be possible…I am overcome with the profundity of the experience…” His enthusiasm for MDMA is especially noteworthy, considering his immense experience with other drugs. Shulgin quickly introduced the drug to several of his psychotherapist friends. His friends were equally awed, and MDMA’s potential as an adjunct to therapy was quickly realized and implemented. During the ‘80s, a small but substantial number of therapists around the country were using MDMA on their patients.

As word spread of the amazing drug, people began to explore its potential use recreationally. During the early 1980s, MDMA was readily available for purchase via 1-800 numbers, convenience stores, and of course, at bars and clubs. Inevitably, the DEA became aware of the situation, and succeeded in making MDMA a Schedule 1 substance, as it remains classified to this today.

But this has far from decreased MDMA’s popularity. The Israeli underground as well as other international organizations control MDMA production and trafficking, and ensure that adequate supplies are available for black market distribution. Despite DEA efforts, and even the occasional bust, the popularity and availability of MDMA is unlikely to die anytime soon. Probably the most unfortunate effect of scheduling is the red tape it puts in front of researchers who wish to investigate MDMA.


3,4-methylenedioxymethamphetamine is a ring-substituted phenylethylamine (PEA). As the chemical name suggests, MDMA consists of a methamphetamine backbone. Despite having some stimulant properties, MDMA produces remarkably different effects than its parent compound. Methamphetamine lacks MDMA’s potent serotonergic effects. This means that adding an ether group to the ring of a PEA at least somewhat determines whether the drug will be serotonergic in nature. Other serotonergic PEA’s, such as mescaline and even the antidepressant venlafaxine (Effexor), both have ether groups around the ring. I mentioned that ether groups “somewhat determine” serotonergic nature because in MDMA, stereochemistry seems to play a big role as well. The (+) enantiomer is more dopaminergic (crossing over with amphetamine) while the (-) enantiomer is more serotonergic (crossing over with mescaline) (1).


Due to the nature of each enantiomer, MDMA has been described as a cross between a stimulant and a hallucinogen. But the Ecstacy experience would rarely be characterized as “seeing cool shit on speed.” Such a label leaves much to be desired, so Dr. David Nichols (one of Shulgin’s close friends) coined the term “entactogen” to classify MDMA, which means, “to touch within” (2). David Pearce has more aptly characterized MDMA as an entactogen-empathogen, referring to both its ability to allow the user to get in touch with himself as well as its ability to increase the empathy one feels for others (3).

While the psychological effects of MDMA are often complex and difficult to characterize clinically, most users report euphoria, increases in energy, self-confidence, extroversion, sexual arousal, and intensity of sensory perception (53, 68).

So what neurochemical activity occurs to produce this so-called entactogen-empathogen effect? Simply stated, MDMA induces the synaptic release of serotonin and dopamine (4,5). Not satisfied? Good—didn’t think you would be. As usual, we’ll go into the details of MDMA’s action on each monoamine and their respective receptor subtypes.


MDMA enters serotonergic neurones via the serotonin re-uptake pump, and reverses the normal direction of monoamine travel, inducing serotonin release (6). MDMA can also block the re-uptake pump, much like an SSRI (7). Recently, it has been shown that up-take inhibition by MDMA contributes to greater increases in 5-HT than direct release (9). Synthesis of 5-HT increases 6-fold upon administration, but falls below baseline shortly thereafter (20). MDMA also inhibits MAO-A, potentiating increases in serotonin (8).

MDMA relies upon indirect stimulation of 5-HT (1B) and 5-HT (2A) receptors to produce its stimulant effects (13). Antagonism of 5-HT (2C) receptors can potentiate MDMA’s dopamine release, but even without 5-HT (2C) antagonism, dopamine release is robust (13).

Probably in response to massive serotonin overflow, a decrease in tryptophan hydroxylase activity is observed following MDMA administration, which explains the reduced synthesis of 5-HT (10). MDMA also inhibits the firing of serotonergic neurons by indirect stimulation of 5-HT (1A) autoreceptors (11,12).


The concentrations of MDMA that are required to induce 5-HT release are 10 times lower than those need to induce dopamine release (21). However, once proper concentrations are achieved, dopamine release is actually greater than 5-HT (22). MDMA-induced increased in dopamine are due to several distinct mechanisms. First, MDMA produces dopamine release and uptake inhibition via the dopamine transporter, independent of any actions by 5-HT (7,14). Second, stimulation of 5-HT (2A) receptors by serotonin increases dopamine synthesis and release (15); when MDMA is administered with a 5-HT (2A) antagonist, dopamine release is attenuated (16). Third, MDMA elicits the release of dopamine from noradrenergic neurons via the NA uptake pump (23). Finally, MAO-B inhibition by MDMA prevents metabolism of dopamine (8).


Effects of MDMA on noradrenaline are similar to that of dopamine, except more potent (22,24): there is NA release that is facilitated by the increase in serotonin (17) and independent of serotonin increase (18). Furthermore, MDMA causes desensitization of a2-adrenoceptors, enhancing noradrenergic transmission (19). MDMA has modest affinity for the a2-adrenoceptor (25), but it is more likely that NA, rather than MDMA, causes the desensitization by acting as a direct agonist (19).


Part of MDMA’s stimulant effects might be due to the release of acetylcholine in the prefrontal cortex and the dorsal striatum, an effect that can be eliminated by the administration of an H1-antagonist (26, 27).

Hormonal Effects

MDMA acutely increases levels of corticosterone, cortisol, prolactin, oxytocin, vasopressin and DHEA (24,64). Corticosterone in particular works very intimately with the 5-HT system, and may modulate many of MDMA’s changes to 5-HT receptors, and even 5-HT neurotoxicity (65).

An interesting observation is that females seem to be much more sensitive to the subjective and neurotoxic effects of MDMA (66). This too is probably related to hormones. Estrogen has a substantial activating effect on 5-HT neurotransmission, upregulating tryptophan hydoxylase, decreasing both 5-HT transporter mRNA and the sensitivity of 5-HT (1A) autoreceptors (67).

For those interested, I intend on exploring the psychoactive and neuromodulatory effects of hormones as well as their implications in gender differences and psychiatric diseases in subsequent edition of Chemically Correct.


MDMA’s half-life is approximately 2.5 hours for the (-) enantiomer and 2.2 hours for the (+) enantiomer (28). Because MDMA has non-linear pharmacokinetics (29), hardcore users who insist upon taking back-to-back doses will experience disproportionately high plasma levels. 50% of MDMA ingested by humans can be recovered unchanged in the urine (29). The other half is metabolized mainly by cytochrome P450 enzyme CPY2D6 to 3,4-methylenedioxyamphetamine (MDA) and 3,4-dihydroxymethamphetamine (HHMA), as well as other minor metabolites (30).


The big question on everyone’s mind might be, “Just how bad is MDMA for your brain?” But before we can answer that question, we need to address some preliminaries.

Definition of Neurotoxicity

The Kleven-Seiden criteria for neurotoxicity of amphetamine analogues has four requirements: 1) long-lasting depletions of 5-HT or dopamine; 2) a decrease in high affinity uptake sites for 5-HT or dopamine; 3) decreased activity of synthetic enzymes for 5-HT or dopamine (i.e. tryptophan or tyrosine hydroxylase); and 4) alterations in neuronal morphology (31).

Evidence of Neurotoxicity

A single 10mg/kg dose to rats produces two waves of 5-HT depletion, one within 3-6 hours after administration with levels returning to normal within a day, and another depletion 1 week after MDMA administration (5). This second wave is also accompanied by a decrease in 5-HT transporters (5). Acute administration in rats also decreases tryptophan hydroxylase (32). Rats taking 80mg/kg twice a day for two days experience degeneration of axon terminals (33). Thus, MDMA fulfills all the requirements for inducing neurotoxicity in rats, albeit at varying dosages.

Full criteria for neurotoxicity is also met in nonhuman primates such as baboons and monkeys, who appear to be much more sensitive to MDMA. Dosages as little as 2.5mg/kg can cause long lasting reductions in 5-HT levels (34).

As for humans, former MDMA users have reduced levels of the major serotonin metabolite 5-HIAA in their cerebrospinal fluid, suggesting 5-HT depletion (35). It has also been demonstrated that human MDMA users have decreased 5-HT uptake site binding compared to controls (36). Such observations would indicate that MDMA users suffer from 5-HT neurotoxicity. But before we say that MDMA is neurotoxic to humans, we should look at the conditions within the studies. The “users” in both studies were extremely experienced, having used MDMA around 200 times, multiple times a month for several years.

Whether the more “typical” user of MDMA (single doses, a few times a year) experiences neurotoxicity remains to be answered definitively.

Mechanisms of Neurotoxicity

Probably unknown to most “Just Say No” zealots is that MDMA by itself is not neurotoxic. When administered directly into the brain, MDMA will induce 5-HT release without any 5-HT neurotoxicity (37). This means that MDMA damage to the 5-HT system requires at least some systemic metabolism. Where, when, and how things go wrong is up for debate, but MDMA metabolites, monoamine metabolites, nitric oxide and hyperthermia probably all play a role. While the major metabolites of MDMA (MDA, HHMA) fail to produce neurotoxicity (38), HHMA can be further metabolized to form quinone-like free radicals, which can produce oxidative stress and membrane damage (39). Such minor toxic metabolites can also irreversibly inhibit tryptophan hydroxylase, which can take up to 2 weeks to recover activity (34,40).

Further oxidative stress on the 5-HT system might be due to dopamine. Blocking MDMA-induced dopamine release will prevent neurotoxic markers such as decreases in tryptophan hydroxylase activity and loss of 5-HT uptake sites (41). Conversely, augmenting dopamine release with L-Dopa will increase neurotoxicity (42). Researchers theorize that high concentrations of dopamine near depleted 5-HT neurons causes a decrease in uptake selectivity, allowing dopamine to enter through the 5-HT transporter. It’s possible that dopamine by itself could act as a foreign toxin to 5-HT neurons, but more likely, MAO-B metabolism of dopamine within the cell produces toxic by-products, including hydrogen peroxide, which increases oxidative stress (43).

MDMA also causes increases in nitric oxide synthase (NOS) in the frontal and parietal cortex (44). Nitric oxide (NO) generates oxidative stress by decreasing glutathione concentrations (45) and producing toxic free radicals via reaction with superoxide (46). Inhibiting NOS with N-nitro-L-arginine prevents MDMA’s neurotoxic effect, but only in the two regions of the brain where NOS is upregulated (44). The role of NO could be related to the toxic effects of dopamine metabolism, as nitric oxide can increase the synthesis of dopamine (47). However, inhibition of NO had no effect on MDMA induced dopamine increases, making it likely that NO has a more direct role in MDMA neurotoxicity (44).

The hyperthermic effect of MDMA is possibly the most acute risk that users face, as it can quickly lead to dehydration or even heat stroke. The extent of hyperthermia depends greatly upon the environmental temperature as well as water intake (48). A less noticeable effect of hyperthermia to the user is depletion of antioxidants in the liver (49). Preventing MDMA-induced hyperthermia with the use of a D1 antagonist blocked neurotoxic changes (50, 34).

MDMA Neuroprotection

A simple and sure way to prevent neurotoxicity is to take an SSRI either before or with MDMA. SSRI’s with long half-lives and active metabolites, such as fluoxetine (Prozac), can provide protection even if MDMA is administered a week after the last SSRI dose (51). Because SSRI’s are neuroprotectant, this implies that entrance of MDMA (or dopamine) via the serotonin re-uptake pump is required to produce neurotoxicity. Further evidence that dopamine is the toxic culprit, and not MDMA itself, lies in the observation that SSRI’s can provide some neuroprotection up to an hour after MDMA administration (52). Such a time frame would coincide more with MDMA’s delayed dopamine release, rather than its immediate penetration of the re-uptake pump.

The only downside to taking an SSRI before or with MDMA is that it largely nullifies the “ecstasy” of the experience (53). No MDMA uptake through the 5-HT transporter equates to no MDMA magic (i.e. serotonin and dopamine release). So unless you’re paranoid about some frat boy slipping MDMA into your drink, SSRI’s probably aren’t the best option for MDMA users looking to have a good time.

The serotonin precursors, 5-HTP and L-tryptophan, are also effective neuroprotectants against MDMA toxicity (62). Unlike the SSRI’s however, 5-HT precursors can actually augment the MDMA experience (63).

Another interesting option is use of the MAO-B inhibitor L-deprenyl. The premise behind this should make sense since we’ve already discussed the role of MAO-B deamination in neurotoxicity. Pretreatment with deprenyl in rats prevents lipid peroxidation as well as deficits in 5-HT, 5-HT transporters and tryptophan hydroxylase (54). For humans, a dose of 5-10mg before MDMA use should be sufficient, although longer use of low-dose deprenyl might be prudent, since it has additional antioxidant effects (55).

While there might be many distinct factors in MDMA neurotoxicity, what ties them together is that they all cause an increase in oxidative stress. Thus, a diverse and complete regimen of antioxidants (possibly even double dosing before and after taking MDMA) wouldn’t be a bad idea. Positive research exists for selenium (56), vitamin C (57), vitamin E (58), zinc (59), alpha lipoic acid (60), and L-cysteine (61). But getting creative and adding other antioxidants like green tea, vitamin A, and grape seed extract would probably help as well.

Other simple precautions, like minimizing exposure to overly hot environments, staying hydrated, and maintaining a good diet could go a long way in preventing toxicity, but are often underrated and ignored


MDMA can be a very life-enriching experience for many, especially when it’s used with intimate friends in a comfortable environment, maximizing the potential for positive self-insight and communication. During its brief popularity in the psychotherapy circle, patients often found that it allowed them to be more honest with themselves and their doctors, confronting issues in a couple of hours which often took years to work up to. For other people, it provides a less than healthy means of escape and self-medication. But for the majority of users, MDMA is just plain fun. But despite all the glowing reviews, MDMA is still a very flawed drug. Even if one is successful in preventing neurotoxicity, the rapid tolerance that one develops minimizes MDMA’s potential for any sort of continued use beyond a handful of times. MDMA does not induce a cocaine-like tolerance, in which users will take more and more to get the same effect. Rather, people just find that MDMA eventually loses its magic, and they stop using the drug.

The real benefits of MDMA won’t be derived from individual use, but rather from continued research on the drug. The amount we can learn from MDMA is far from being realized; MDMA research stands to elucidate many aspects of neuroadaptation and toxicity; the 5-HT and dopaminergic systems, and their involvement in mood and psychopathology. MDMA could even influence the development of future pharmaceuticals for mood disorders. Imagine a non-neurotoxic drug that implemented MDMA’s powerful and fast acting effects on 5-HT and dopamine. It would place Prozac and Ritalin into the realms of castor oil and bloodletting. But such a future isn’t here yet. So until then, take your antioxidants, stay hydrated, and “roll” safely.


1. Baker LE, Taylor MM. Assessment of the MDA and MDMA optical isomers in a stimulant-hallucinogen discrimination. Pharmacol Biochem Behav. 1997 Aug;57(4):737-48.
2. Nichols DE, Hoffman AJ, Oberlender RA, Jacob P 3rd, Shulgin AT.
J Med Chem 1986 Oct;29(10):2009-15.
3. Pearce D. Utopian Pharmacology: Mental Health in the Third Millenium, MDMA and Beyond.
4. Nichols DE, Lloyd DH, Hoffman AJ, Nichols MD, Yim GKW. Effects of certain hallucinogenic amphetamine analogues on the release of [3H]-serotonin from rat brain synaptosomes. J Med Chem. 1982;25:530-535.
5. Schmidt C. Neurotoxicity of the psychedelic amphetamine, MDMA. J Pharmacol Exp Ther. 1987;240:1-7.
6. Schmidt CJ, Kehne JH. Neurotoxicity of MDMA: neurochemical effects. Annals of the New York Academy of Sciences. 1990;600:665-680.
7. Steele TD, Nichols DE, Yim GKW. Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of (3H)monoamine into synaptosomes from different regions of rat brain. Biochem Pharmacol. 1987 Jul 15;36(14):2297-303.
8. Leonardi ET, Azmitia EC. MDMA (ecstasy) inhibition of MAO type A and type B: comparisons with fenfluramine and fluoxetine (Prozac). Neuropsychopharmacology. 1994 Jul;10(4):231-8.
9. Iravani MM, Asari D, Patel J, Wieczorek WJ, Kruk ZL. Direct effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin or dopamine release and uptake in the caudate putamen, nucleus accumbens, substantia nigra pars reticulata, and the dorsal raphe nucleus slices. Synapse. 2000 Jun 15;36(4):275-85.
10. Schmidt CJ, Taylor VL. Depression of rat brain tryptophan hydroxylase activity following the acute administration of methylenedioxymethamphetamine. Biochem Pharmacol. 1987 Dec 1;36(23):4095-102.
11. Aguirre N, Galbete JL, Lasheras B, Del Rio J. Methylenedioxymethamphetamine induces opposite changes in central and pre- and postsynaptic 5-HT(1A) receptors in rats. Eur. J Pharmacol. 281, 101-105.
12. Millan MJ, Colpaert FC. Methylenedioxymethamphetamine induces spontaneous tail-flicks in the rat via 5-HT1A receptors. Eur J Pharmacol. 1991 Feb 7;193(2):145-52.
13. Fletcher PJ, Korth KM, Robinson SR, Baker GB. Multiple 5-HT receptors are involved in the effects of acute MDMA treatment: studies on locomotor activity and responding for conditioned reinforcement. Psychopharmacology (Berl). 2002 Jul;162(3):282-91.
14. Nash JF, Brodkin J. Microdialysis studies on 3,4-methylenedioxymethamphetamine-induced dopamine release: effect of dopamine uptake inhibitors. J. Pharmacol Exp Ther. 1991;259:820-5.
15Gudelsky GA, Nash JF. Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine: implications for serotonin-dopamine interactions. J Neurochem. 1996;66:243-9.
16. Nash JF. Ketanserin pretreatment attenuates MDMA-induced dopamine release in the striatum as measured by in vivo microdialysis. Life Sci. 1990;47:2401-8.
17. Done CJG, Sharp T. Biochemical evidence for the regulation of central noradrenergic activity by 5-HT1 and 5-HT2 receptors: microdialysis studies in the awake and anaesthetised rat. Neuropharmacology1994;33:411–21.
18. Fitzgerald JL, Reid JJ. Effects of methylenedioxymethamphetamine on the release of monoamines from rat brain slices. Eur J. Pharmacol. 1990;191:217-20.
19. Arrue A, Ruiz-Ortega JA, Ugedo L, Giralt MT. Short-term effects of 3,4-methylenedioximethamphetamine on noradrenergic activity in locus coeruleus and hippocampus of the rat. Neurosci Lett. 2003 Feb 13;337(3):123-6.
20. Nishisawa S, Mzengeza S, Diksic M. Acute effects of 3,4-methylenedioxymethamphetamine on brain serotonin synthesis in the dog studied by positron emission tomography. Neurochem Int. 1999 Jan;34(1):33-40.
21. Schmidt CJ, Levin JA, Lovenberg W. In vitro and in vivo neurochemical effects of methylenedioxymethamphetamine on striatal monoaminergic systems in the rat brain. Biochem Pharmacol. 1987 Mar 1;36(5):747-55.
22. Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 2001 Jan;39(1):32-41.
23. Shankaran M, Gudelsky GA. Effect of 3,4-methylenedioxymethamphetamine (MDMA) on hippocampal dopamine and serotonin. Pharmacol Biochem Behav. 1998 Dec;61(4):361-6.
24. Cole JC, Sumnall HR. The pre-clinical behavioural pharmacology of 3,4-methylenedioxymethamphetamine (MDMA). Neurosci Biobehav Rev. 2003 May;27(3):199-217.
25. Lavelle A, Honner V, Docherty JR. Investigation of the prejunctional alpha2-adrenoceptor mediated actions of MDMA in rat atrium and vas deferens. Br J Pharmacol. 1999 Nov;128(5):975-80.
26. Acquas E, Marrocu P, Pisanu A, Cadoni C, Zernig G, Saria A, Di Chiara G. Intravenous administration of ecstasy (3,4-methylendioxymethamphetamine) enhances cortical and striatal acetylcholine release in vivo. Eur J Pharmacol. 2001 Apr 27;418(3):207-11.
27. Fischer HS, Zernig G, Schatz DS, Humpel C, Saria A. MDMA (‘ecstasy’) enhances basal acetylcholine release in brain slices of the rat striatum. Eur J Neurosci. 2000 Apr;12(4):1385-90.
28. Esteban B, O’Shea E, Camarero J, Sanchez V, Green AR, Colado MI. 3,4-Methylenedioxymethamphetamine induces monoamine release, but not toxicity, when administered centrally at a concentration occurring following a peripherally injected neurotoxic dose. Psychopharmacology (Berl). 2001 Mar;154(3):251-60.
29. de la Torre R, Farre M, Ortuno J, Mas M, Brenneisen R, Roset PN, Segura J, Cami J. Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans. Br J Clin Pharmacol. 2000 Feb;49(2):104-9.
30. Kreth K, Kovar K, Schwab M, Zanger UM. Identification of the human cytochromes P450 involved in the oxidative metabolism of “Ecstasy”-related designer drugs. Biochem Pharmacol. 2000 Jun 15;59(12):1563-71.
31. Hegadoren KM, Baker GB, Bourin M. 3,4-Methylenedioxy analogues of amphetamine: defining the risks to humans. Neurosci Biobehav Rev. 1999 Mar;23(4):539-53.
32. Schmidt CJ, Taylor VL. Depression of rat brain tryptophan hydroxylase activity following the acute administration of methylenedioxymethamphetamine. Biochem Pharmacol. 1987 Dec 1;36(23):4095-102.
33. Commins DL, Vosmer G, Virus RM, Woolverton WL, Schuster CR, Seiden LS. Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. J Pharmacol Exp Ther. 1987 Apr;241(1):338-45.
34. Lyles J, Cadet JL. Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms. Brain Res Brain Res Rev. 2003 May;42(2):155-68.
35. McCann UD, Mertl M, Eligulashvili V, Ricaurte GA. Cognitive performance in (+/-) 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) users: a controlled study. Psychopharmacology (Berl). 1999 Apr;143(4):417-25.
36. McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte GA. Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings. Lancet. 1998 Oct 31;352(9138):1433-7.
37. Esteban B, O’Shea E, Camarero J, Sanchez V, Green AR, Colado MI. 3,4-Methylenedioxymethamphetamine induces monoamine release, but not toxicity, when administered centrally at a concentration occurring following a peripherally injected neurotoxic dose. Psychopharmacology (Berl). 2001 Mar;154(3):251-60.
38. McKenna DJ, Peroutka SJ. Neurochemistry and neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). J Neurochem. 1990 Jan;54(1):14-22.
39. Hiramatsu M, Kumagai Y, Unger SE, Cho AK. Metabolism of methylenedioxymethamphetamine: formation of dihydroxymethamphetamine and a quinone identified as its glutathione adduct. J Pharmacol Exp Ther. 1990 Aug;254(2):521-7.
40. Schmidt CJ, Taylor VL. Depression of rat brain tryptophan hydroxylase activity following the acute administration of methylenedioxymethamphetamine. Biochem Pharmacol. 1987 Dec 1;36(23):4095-102.
41. Brodkin J, Malyala A, Nash JF. Effect of acute monoamine depletion on 3,4-methylenedioxymethamphetamine-induced neurotoxicity. Pharmacol Biochem Behav. 1993 Jul;45(3):647-53.
42. Schmidt CJ, Black CK, Taylor VL. L-DOPA potentiation of the serotonergic deficits due to a single administration of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine or methamphetamine to rats. Eur J Pharmacol. 1991 Oct 2;203(1):41-9.
43. Sprague JE, Everman SL, Nichols DE. An integrated hypothesis for the serotonergic axonal loss induced by 3,4-methylenedioxymethamphetamine. Neurotoxicology. 1998 Jun;19(3):427-41.
44. Zheng Y, Laverty R. Role of brain nitric oxide in (+/-)3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity in rats. Brain Res. 1998 Jun 8;795(1-2):257-63.
45. Gegg ME, Beltran B, Salas-Pino S, Bolanos JP, Clark JB, Moncada S, Heales SJ. Differential effect of nitric oxide on glutathione metabolism and mitochondrial function in astrocytes and neurones: implications for neuroprotection/neurodegeneration? J Neurochem. 2003 Jul;86(1):228-37.
46. Vincent SR. Nitric oxide: a radical neurotransmitter in the central nervous system. Prog Neurobiol. 1994 Jan;42(1):129-60.
47. Kim D, Choi HJ, Kim SW, Cho SW, Hwang O. Upregulation of catecholamine biosynthetic enzymes by nitric oxide. J Neurosci Res. 2003 Apr 1;72(1):98-104.
48. Dafters RI. Hyperthermia following MDMA administration in rats: effects of ambient temperature, water consumption, and chronic dosing. Physiol Behav. 1995 Nov;58(5):877-82.
49. Carvalho M, Carvalho F, Remiao F, de Lourdes Pereira M, Pires-das-Neves R, de Lourdes Bastos M. Effect of 3,4-methylenedioxymethamphetamine (“ecstasy”) on body temperature and liver antioxidant status in mice: influence of ambient temperature. Arch Toxicol. 2002 Apr;76(3):166-72.
50. Nash JF Jr, Meltzer HY, Gudelsky GA. Elevation of serum prolactin and corticosterone concentrations in the rat after the administration of 3,4-methylenedioxymethamphetamine. J Pharmacol Exp Ther. 1988 Jun;245(3):873-9.
51. Sanchez V, Camarero J, Esteban B, Peter MJ, Green AR, Colado MI. The mechanisms involved in the long-lasting neuroprotective effect of fluoxetine against MDMA (‘ecstasy’)-induced degeneration of 5-HT nerve endings in rat brain. Br J Pharmacol. 2001 Sep;134(1):46-57.
52. Schmidt CJ, Taylor VL. Reversal of the acute effects of 3,4-methylenedioxymethamphetamine by 5-HT uptake inhibitors. Eur J Pharmacol. 1990 May 31;181(1-2):133-6.
53. Liechti ME, Baumann C, Gamma A, Vollenweider FX. Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) are attenuated by the serotonin uptake inhibitor citalopram. Neuropsychopharmacology. 2000 May;22(5):513-21.
54. Sprague JE, Nichols DE. The monoamine oxidase-B inhibitor L-deprenyl protects against 3,4-methylenedioxymethamphetamine-induced lipid peroxidation and long-term serotonergic deficits. J Pharmacol Exp Ther. 1995 May;273(2):667-73.
55. Carrillo MC, Kitani K, Kanai S, Sato Y, Miyasaka K, Ivy GO. The effect of a long term (6 months) treatment with (-)deprenyl on antioxidant enzyme activities in selective brain regions in old female Fischer 344 rats. Biochem Pharmacol. 1994 Apr 20;47(8):1333-8.
56. Sanchez V, Camarero J, O’Shea E, Green AR, Colado MI. Differential effect of dietary selenium on the long-term neurotoxicity induced by MDMA in mice and rats. Neuropharmacology. 2003 Mar;44(4):449-61.
57. Shankaran M, Yamamoto BK, Gudelsky GA. Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT. Synapse. 2001 Apr;40(1):55-64
58. Johnson EA, Shvedova AA, Kisin E, O’Callaghan JP, Kommineni C, Miller DB. d-MDMA during vitamin E deficiency: effects on dopaminergic neurotoxicity and hepatotoxicity. Brain Res. 2002 Apr 19;933(2):150-63.
59. Jayanthi S, Ladenheim B, Andrews AM, Cadet JL. Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (Ecstasy). Neuroscience 1999;91(4):1379-87
60. Aguirre N, Barrionuevo M, Ramirez MJ, Del Rio J, Lasheras B. Alpha-lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity. Neuroreport. 1999 Nov 26;10(17):3675-80.
61. Gudelsky GA. Effect of ascorbate and cysteine on the 3,4-methylenedioxymethamphetamine-induced depletion of brain serotonin. J Neural Transm. 1996;103(12):1397-404.
62. Sprague JE, Huang X, Kanthasamy A, Nichols DE. Attenuation of 3,4-methylenedioxymethamphetamine (MDMA) induced neurotoxicity with the serotonin precursors tryptophan and 5-hydroxytryptophan. Life Sci. 1994;55(15):1193-8.
63. Sprouse JS, Bradberry CW, Roth RH, Aghajanian GK. 3,4-Methylenedioxymethamphetamine-induced release of serotonin and inhibition of dorsal raphe cell firing: potentiation by L-tryptophan. Eur J Pharmacol. 1990 Mar 27;178(3):313-20.
64. Harris DS, Baggott M, Mendelson JH, Mendelson JE, Jones RT. Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl). 2002 Aug;162(4):396-405.
65. Yau JL, Noble J, Seckl JR. Site-specific regulation of corticosteroid and serotonin receptor subtype gene expression in the rat hippocampus following 3,4-methylenedioxymethamphetamine: role of corticosterone and serotonin. Neuroscience. 1997 May;78(1):111-21.
66. Liechti ME, Gamma A, Vollenweider FX. Gender differences in the subjective effects of MDMA. Psychopharmacology (Berl). 2001 Mar 1;154(2):161-8.
67. McEwen B. Estrogen actions throughout the brain. Recent Prog Horm Res. 2002;57:357-84.
68. Cohen RS. Subjective reports on the effects of the MDMA (‘ecstasy’) experience in humans. Prog Neuropsychopharmacol Biol Psychiatry. 1995 Nov;19(7):1137-45.