But it doesn't mean that it does either Dan. There are conflicting studies both ways. There are theories that some "damage" can occur to the hippocampus, and others that say there is long term SERT damage. To say that it causes brain damage for sure, suggesting it is long term and irreversable is IRRESPONSIBLE. Alcohol is neurtoxic and that is well documented, but you don't see Dr Drew doing a Public service announcement on that. What I have a problem with is what he is insinuating: You do ecstasy and you will turn into a babbling moron."" Read up a little bit more first, then come back to me. Here are some things to consider, as written by Adam X on another site:
As far as actual mechanisms of neurotoxicity, I like the toxic metabolite theory, possibly MDA, or a metabolite thereof. MDA is neurotoxic, this has been demonstrated in vitro and in vivo. MDMA, as we're all aware, is metabolized to MDA. No studies have been undertaken to assess the neurotoxicity of MDMA when conversion to MDA is inhibited, so this question remains unanswered.
It's my theory that Deprenyl (at selective dosages) inhibits the conversion of MDMA to MDA, or inhibits the conversion of MDA to its toxic metabolite(s), although not through MAO-B inhibition. MAO-B is highly selective, preferring phenethylamine and dopamine to serotonin and norepinephrine. MDMA is a phenethylamine, but so is amphetamine, and much more closely so. Deprenyl does not appear to appreciably inhibit the metabolism of methamphetamine or amphetamine, if it did amphetamine levels would build very rapidly to very high levels after frequent Deprenyl administration since amphetamine and methamphetamine are metabolites of Deprenyl. Toxic psychosis would be an eventual result of long-term Deprenyl administration. Furthermore, direct inhibition of MAO-B by Deprenyl does not increase the effects of either drug. Therefore I think we can safely rule out MAO-B.
Aside from inhibiting MAO-B, Deprenyl induces dozens of enzymatic changes. Deprenyl is not specifically an MAO-B inhibitor, it seems to inhibit some enzymes while inducing others (1) (eg. superoxide dismutase). It could be that this "beefing up" of the brain's own natural antioxidant capabilites are responsible for the neuroprotective effects of Deprenyl with regard to MDMA. Unfortunately, I don't think this is the case. Deprenyl increases SOD (superoxide dismutase) apparantly by altering expression of SOD 1 and 2 genes. This would seem to be a process which may take several days or weeks before maximum protection occurs. To the best of my knowledge, pretreatment with a single dose of Deprenyl is adequate to prevent MDMA induced neurotoxicity, AND, a single dose of Deprenyl effectively inhibits enzymes beginning immediately. If it were the altered gene expression of SOD 1 and 2, as opposed to an ezymatic factor, then this single pretreatment with Deprenyl would not prevent MDMA induced neurotoxicity.
Another possibility is that the "neurotoxic" actions of MDMA/MDA are mediatied via apoptosis. Deprenyl seems to inhibit this, possibly by blocking the mitochondrial signals which initiate this (3). This is another theory I find lacking however, since studies on Deprenyl and apoptosis utilized P450 blockers, thereby preventing the extensive first pass metabolism of Deprenyl. Studies on Deprenyl and apoptosis without P450 inhibitors are needed for further clarification.
Finally, it very well may be that it's the "upregulation" of SOD and other antioxidant enzymes is the method by which Deprenyl inhibits MDMA neurotoxicity. Certainly the method of damage is membrane lipid peroxidation subsequest to free radical formation, the only question is: How are the radicals being formed? Again, the problem of time comes into play. I find it hard to believe that a single treatment of Deprenyl markedly increases SOD gene expression.
I don't have any direct evidence to support any of these theories, though I suspect if I had enough time and were so inclined I could find supporting evidence if I looked long enough. If I had to pick and choose one answer, it would be the following:
MDMA metabolites induce neurotoxic membrane lipid peroxidation when the antioxidant capabilities of the brain are overwhelmed. Heat, stress, diet, basal metobolic rate and other factors play a key role in the amount of free radicals which can be mopped up before damage occurs. Pretreatment supplementation with massive amounts of vitamin C and vitamin E have been shown to reduce or eliminate altogether this membrane lipid peroxidation.
MDMA is metabolized into a toxic metabolite via a key enzyme or enzymes, after which it is taken up into the serotonin axon. If the antioxidant capabilities of the brain are overwhelmed, (mitochondrial ?) extensive free radical oxidation occurs, resulting in the eventual destruction of the axon. If it's mitochondrial damage, then it very well may be apoptosis which is responsible for the "death" of the axon. The axon cannot survive without the mitochondria.
Deprenyl inhibits some enzymes, while inducing others. Deprenyl likely inhibits a key enzyme responsible for the conversion of MDMA into it's toxic metabolite(s). This enzyme (or enzymes) is not the sole metabolic pathway for elimiating MDMA, it may not even be the preferred, but it's probably the fastest. It's likely not MAO-B, due to the reasons offered above. Apparantly, the key to unlocking the secret of MDMA neurotoxicity lies in unlocking the secret of Deprenyl in MDMA neuroprotection, or at least in determining every single enzyme involved in the metabolism of MDMA
X
1. 'Histamine N-methyltransferase: inhibition by monoamine oxidase inhibitors'; Agents Actions. 1993 Sep;40(1-2):1-10.
2. 'METHYLATION PHARMACOGENETICS: Catechol O-Methyltransferase, Thiopurine Methyltransferase, and Histamine N-Methyltransferase' Annu. Rev. Pharmacol. Toxicol. 1999. 39:19–52
3. 'Modulation of gene expression rather than monoamine oxidase inhibition: (-)-Deprenyl-related compounds in controlling neurodegeneration'; Neurology (USA), 1996, 47/6 SUPPL. 3 (S171-S183)
As you can see, there is much to be considered. It is way to early to make declarations about anything when X is involved. It is unclear what damage occurs, what effect said damage would have, the mechanisms through which this damage occurs, what doses one would have to take if it did, which is further compounded by study methods including, but not limited to: Polydrug users being studied and then singling out Ecstasy as the root cause, Animal's being administered extremely high doses directly into the blood stream, shoddy research methods, conflicting results etc.
So yes, I call that irresponsible.
