Posted by Larry Hoover on August 29, 2004, at 20:31:34
In reply to Re: Ecstasy safely converted and prescribed?, posted by verne on August 29, 2004, at 19:50:19
> There's nothing "safe", "useful", or "positive" about ecstasy as the chemist suggests.
>
> I don't know the chemistry but ecstasy uses up something in the brain having to do with the capacity to feel pleasure. "Holes" in the brain are readily visible in those who've taken even a few doses.
>
> And as pointed out already in this thread, untreatable depression is the result.The two factors which must be present, for brain damage to occur, are either or both of, a very high single dose, and repeated dosing without a recovery period between doses.
The first abstract below demonstrates this relationship nicely. Note that the threshold for brain damage, or even abnormal brain chemistry post-use, is greater than 4 mg/kg (by interperitoneal injection, not oral), a dose three times the typical human dose, employing a route of intake not normally employed by humans. Only repeated use, far in excess of that frequency used by any but the most committed clubbers, caused measurable changes in brain chemistry. The authors conclude, "We suggest that damage occurs when endogenous free radical scavenging mechanisms become overwhelmed or exhausted." In other words, antioxidant levels can be used up, if you overdo it. That's what leads to the damage, not the acute drug effects.
The second one makes two very clear points. Prior to its publication, only two studies had shown neurological damage from MDMA, and only following *very high doses*, not specified in the abstract.
By no means am I saying that makes MDMA safe, but dose (and frequency of dose) make the poison. The post-MDMA depletion of serotonin is not permanent. Your body will make as much as it needs, within no more than 48 hours.
Lar
Neuropharmacology. 1998 Jul;37(7):919-26.
The relationship between the degree of neurodegeneration of rat brain 5-HT nerve terminals and the dose and frequency of administration of MDMA ('ecstasy').O'Shea E, Granados R, Esteban B, Colado MI, Green AR.
Departamento de farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
The effect of varying the dose and frequency of administration of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') on both the acute hyperthermic response and the long term neurodegeneration of 5-hydroxytryptamine (5-HT) nerve terminals in the brain has been studied in Dark Agouti rats. A single injection (4-15 mg/kg i.p.) of MDMA produced immediate dose-related hyperthermia and a dose-related decrease in 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and [3H]paroxetine binding in regions of the brain 7 days later, with a dose of 4 mg/kg having no degenerative effect. This dose was also without effect when given once daily for 4 days, but produced a marked loss of [3H]paroxetine binding and indole concentration ( approximately 55%) when given twice daily for 4 days. When a dose of 4 mg/kg was given twice weekly for 8 weeks it had no effect on these serotoninergic markers, despite a clear anorectic effect of the drug being seen. These data demonstrate that MDMA-induced neurodegeneration is related to both the dose and frequency of administration and indicate that damage to 5-HT neurones can occur in the absence of a hyperthermic response to the drug. We suggest that damage occurs when endogenous free radical scavenging mechanisms become overwhelmed or exhausted.
Brain Res. 2003 Jun 6;974(1-2):127-33.
Demonstration and localization of neuronal degeneration in the rat forebrain following a single exposure to MDMA.Schmued LC.
Department of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA. lschmued@nctr.fda.gov
Methylenedioxymethamphetamine (MDMA, Ecstasy) is a powerful releaser of serotonin. Increasing recreational use of this stimulant and hallucinogenic drug has raised concerns about its potential to produce brain damage. The vast majority of previous research studies have focused on the compound's ability to deplete serotonin (5-hydroxytryptamine, 5-HT) from axon terminals. Despite extensive research on this '5-HT terminal neurotoxicity', a much less studied aspect of MDMA toxicity involves its ability to actually kill nerve cells. Only two prior studies mention the existence of MDMA-induced neuronal degeneration, as reflected by a limited number of argyrophylic neurons within the somatosensory cortex, following very high doses of MDMA. The development of Fluoro-Jade B as a simple and reliable marker of neuronal degeneration has allowed us to conduct the first comprehensive localization of MDMA induced neuronal degeneration throughout the entire rat forebrain. In addition to the previously reported neuronal degeneration within parietal cortex, degenerating neurons were also observed in the insular/perirhinal cortex, the ventromedial/ventrolateral thalamus, and the tenia tecta. The extent of neuronal degeneration observed generally correlated with the degree of hyperthermia achieved.
poster:Larry Hoover
thread:383476
URL: http://www.dr-bob.org/babble/20040825/msgs/383848.html