Has anyone become stupid here?

[sabre]

What I mean is, "E" fucks up all of the neurologics in your head. That is proven fact. That won't stop me of course, but I'm curious if "E" has effected your every day life. This question is aimed more towards long time users, but if new people feel stupid or bad after, I'd like to know

[e-tarded]

You need to do alot more research before you go posting.

What I mean is, "E" fucks up all of the neurologics in your head. That is proven fact.

Neuro-transmitters is the word you were looking for possibly.

Neurotoxicity

MDMA is unambiguously neurotoxic in lab animals in high doses. Typical dose regimens which elicit neurotoxicity are 20mg/kg (rats) or 5mg/kg (primates) given twice daily for four days either i.m. (intramuscularly) or s.c. (subcutaneously). Humans typically use MDMA p.o (per oral) and at levels of about 2.5 mg/kg or less. Subcutaneous administration of MDMA tends to increase toxicity 2-3 times over p.o.[1] Extrapolation of animal studies to human use is difficult, since humans typically use a less toxic route of administration, take somewhat less per dose and take a smaller cumulative dose.

One study of MDMA administered to primates most closely modelled human use and used doses of 2.5mg/kg given every 2 weeks for 4 months (2.5 mg/kg x 8) which found no evidence of neurotoxicity[2]. A single- dose study found a decrease in serotonin (5-HT) and it's major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in rhesus monkeys at 5mg/kg but not 2.5mg/kg. Another study gave rhesus monkeys 2.5mg/kg twice daily for four days and found depletions of 5-HT and 5-HIAA, but without any evidence of neurotoxicity from [3H]paroxetine binding to the 5-HT reuptake transporter[3]. The finding that depletions of 5-HIAA could occur in the absense of 5-HT neurotoxicity creates problems in interpreting the results of CSF 5-HIAA reductions in human users, which remains the strongest evidence of putative MDMA neurotoxicity in humans[4].

Other results of human studies in MDMA users are at odds with the conclusion that MDMA is a human neurotoxin. McCann, et al. in the same study which analyzed CSF 5-HIAA, found that MDMA users tended to have better impulse control and lower hostility while lower serotonin levels are thought to be correlated with increased hostility. A study of sleep patterns of MDMA users found that MDMA users had normal sleep patterns, but with a statistically significant decrease in stage 2 sleep, leading to an overall improvement in sleep quality -- more importantly these results are not at all in accordance with studies on sleep patterns of humans given the 5-HT supressor para-chlorophenylalanine (PCPA) or with animals having lesioned 5-HT systems[5].

Prospective studies (giving users MDMA in a controlled environment with baseline testing and then checking for indications of neurotoxicity) rather than retrospective studies (after the fact with no baseline) are only just getting underway at the Harbor-UCLA medical center (other studies are starting in England, Switzerland and Germany[6]). Initial retrospective results of the UCLA study indicate that MDMA may increase cerebral blood flow [7]. This may be indicative of benficial rather than neurotoxic changes in the brain:

We are aware of a variety of neuro-psychiatric disorders associated with measurements of low blood flow, including Alzheimer's Disease, HIV Dementia, Major Depressive Disorders and Chronic Cocaine Abuse. However, there are no known clinical disorders or drugs which induce long-term elevations of rates of cerebral blood flow. -- Charles S. Grob.

There have been reports of adverse psychiatric effects in the literature particularly anxiety attacks, paranoia and depression. However, some cases present the onset of psychiatric symptoms after a single typical dose[8] which suggests a psychological rather than biological/neurotoxic mechanism. Also, some cases of paranoia reported appear to have occured after repeated daily abuse and probably represent a manifestation of amphetamine psychosis, possibly in part due to adulteration or substitution by amphetamines[9].

The diet drug d-fenfluramine (Redux) causes similar effects on the 5-HT system, and it has been suggested that the lack of adverse psychiatric effects to chronic ingestion of d-fenfluramine implies that MDMA is probably without adverse effects. However, it appears that the mechanism behind MDMA and d-fenfluramine neurotoxicity are not the same, and this may make extrapolation from one drug to the other problematic[10].

To summarize the clinical data, the available evidence tends to suggest that in human users a (probably reversable) decrease in 5-HT may occur (possibly via suppression of the enzyme tryptophan hydroxylase) but that 5-HT neurons remain functionally intact. However, neurotoxic levels in humans are probably "attainable" and the exact amount of MDMA required to elicit a neurotoxic response in humans is unknown.

The exact mechanism of MDMA neurotoxicity in animals is not presently known [11], but it seems to require dopamine activity, oxidation, and access to the 5-HT transporter. Increasing dopamine activity via ingestion of methamphetamine, l-tyrosine, phenylalanine or l-dopa would tend to increase MDMA neurotoxicity. This is a concern since phenylalanine is in diet soft drinks and products sweeted with aspartame and is also in many "smart drinks" sold at raves and of course methamphetamine is a concern since MDMA is often cut with crystal. On the other hand ascorbate (vitamin C) and l-cystine which are anti-oxidants have been shown to prevent MDMA induced neurotoxicity in animals, as has the administration of a SSRI antidepressant (Prozac, Zoloft, Paxil, Luvox, etc.). Studies indicate that taking either an anti-oxidant or a SSRI up to 5 hours after taking MDMA will prevent neurotoxicity in animals[12].

It may be sensible irregardless of if MDMA is neurotoxic in humans for users to take an antioxidant (e.g. 2-4 g vitamin C, orange juice) along with some 5-HT precursors (l-trytophan or 5-hydroxytryptophan (5-HTP), bananas, milk).

1. Ricaurte, GA, DeLanney, LE, Irwin, I, Langston, JW. "Toxic Effects of MDMA on Central Serotonergic Neurons in the Primate: Importance of Route and Frequency of Drug Administration," Brain Research, Vol 446, P165-168, 1988.

2. Ricarute, GA, personal communication on the findings of an unpublished study.

3. Insel, TR, Battaglia, G, Johannessen, JN, Marra, S, DeSouza, EB, "3,4-Methylenedioxymethamphetamine (Ecstasy) Selectively Destroys Brain Serotonin Terminals in Rhesus Monkeys," Journal of Pharmacology and Experimental Therapeutics, Vol 249(1), P 713-720, 1989.

4. McCann, UD, Ridenour, A, Shaham, Y, Ricaurte, GA. "Serotonin neurotoxicity after (+/-) 3,4-methylenedioxy-methamphetamine (MDMA, Ecstasy): a controlled study in humans," Neuropsychopharmacology, Vol 10(2), P 129-138, 1994.

5. Allen, RP, McCann, UD, Ricaurte, GA, "Persistent effects of (+-) 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) on human sleep," Sleep, Vol 16(6), P 560-564.

6. MAPS Newslatter Vol 6, No 3, Summer 1996. http://www.maps.org/news-letters/v06n3/

7. MAPS Newsletter Vol 5, No 4, Summer 1995. http://www.maps.org/news-letters/v05n4/05402mdm.html. Grob-C-S, Poland-R-E Chang-L, Ernst-T, "Psychobiologic effects of 3,4-methylenedioxymethamphetamine in humans: methodological considerations and preliminary observations," Behav. Brain Res., 1996 73(1-2), P 103-7.

8. McCann-U-D, Ricaurte-G-A, "MDMA ('ecstasy') and panic disorder: induction by a single dose," Biol. Psychiatry 1992 Nov 15 32(10):950-3.

9. McGuire-P-K, Cope-H, Fahy-T-A, "Diversity of psychopathology associated with use of 3,4-methylenedioxymethamphetamine ('Ecstasy')," Br. J. Psychiatry, 1994 Sep 165(3):391-5.

10. Colado-M-I, O'Shea-E, Granados-R, Murray-T-K, Green-A-R, "In vivo evidence for free radical involvement in the degeneration of rat brain 5-HT following administration of MDMA ('ecstasy') and p-chloroamphetamine but not the degeneration following fenfluramine," Br. J. Pharmacol., 1997 Jul 121(5):889-900.

11. Seiden-L-S, Sabol-K-E, "Methamphetamine and methylenedioxymethamphetamine neurotoxicity: possible mechanisms of cell destruction," NIDA Res. Monogr. 1996 163:251-76.

12. Gudelsky-G-A, "Effect of ascorbate and cysteine on the 3,4-methylenedioxymethamphetamine-induced depletion of brain serotonin," J. Neural Transm., 1996 103(12), P 1397-404. McCann-U-D, Ricaurte-G-A, "Reinforcing subjective effects of (+/-) 3,4-methylenedioxymethamphetamine ('ecstasy') may be separable from its neurotoxic actions: clinical evidence." J. Clin. Psychopharmacol. 1993 Jun 13(3):214-7. Schmidt-C-J, Kehne-J-H, "Neurotoxicity of MDMA: neurochemical effects.", Ann. N.Y. Acad. Sci. 1990 600:665-80. Steranka-L-R, Rhind-A-W, "Effect of cysteine on the persistent depletion of brain monoamines by amphetamine, p-chloroamphetamine and MPTP," Eur. J. Pharmacol. 1987 Jan 13 133(2):191-7. Battaglia-G, Yeh-S-Y, De-Souza-E-B, "MDMA-induced neurotoxicity: parameters of degeneration and recovery of brain serotonin neurons," Pharmacol. Biochem. Behav. 1988 Feb 29(2):269-74.

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~*P*L*U*R*~

Four Simple Words To Live By....

[PinkFloyd40]

yes, me thinks it haz makes me dummer

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"And thus they give the time, that Nature meant

For peaceful sleep and meditative snores,

To ceaseless din and mindless merriment

And waste of shoes and floors."

[sinergygrl]

E tarded...

Thank you for the very informative post. I think there a lot of people out there that need to research things a little more before they go putting shit into their bodies. It amazes me how ignorant so many people are. Naturally there are consiquences to everything, and you need to know what they are.

To the person who made the first post, read over what e tarded posted, what you don't understand get a dictionary and start looking up the shit. It sounds like you don't know a whole lot about what you are doing, and that is scary. I may be wrong, but your post really makes me wonder. Because obviously you haven't understood a damn thing you have read so far.

I have rolled quite a bit, but I only do it once a month, I think there has been a couple times I did it twice a month. I know htat no matter what this drug is going to have some sort of negative effect on my body, but why make it worse by being stupid. I do everything possible to make sure I can do it responsibly. Well... as responsible as you can do an illegal drug. It helps a lot because my boyfriend is in med school and can get me a lot of information on things that actually comes from medical research instead of some web page that could be hearsay.

I didn't mean to be rude, but you have to know what you are doing or you shouldn't be doing it.

-SIN