Posted by PsychoSage on April 7, 2004, at 0:00:26
In reply to Re: Super LINKAGE - ecstasy+effexor is a NO-NO, posted by djmmm on April 6, 2004, at 20:54:20
Okay, I am sorry if I went off on the neurotoxicity tangent, but the whole point of some people's abuse of SSRI's is to counteract the consequences of the abuse of ecstasy which is not quite the same thing as MDMA all the time.
THE ISSUE HERE IS EFFEXOR AND E. NOT NEUROTOXICITY OR NEURODEGENERATION. SEROTONIN SYNDROME IS THE ISSUE!
SEROTONIN SYNDROME CAN BE MILD OR FATAL!
THE ISSUE IS NOT WHETHER OR NOT PROZAC CAN RESTORE SEROTONIN LEVELS.
Rational people contend that serotonin syndrome of varying degrees {just like drunkenness can occur in varying degrees}
can occur when an SSRI or SNRI like Effexor is taking in conjunction with MDMA or street ecstasy.Were these MICE on SSRI therapy before they were given the SSRI with the MDMA?
What are the side effects for Mice who are on SSRI therapy before they have any MDMA when they take a dose of MDMA and the SSRI?
They can't be the same for SSRI abstinent mice. One dose of an SSRI versus many doses over many months which produce a steady state will be the difference between night and day.
Neurodegeneration and serotonin syndrome are TWO DIFFERENT THINGS. Isn't neurodegeneration aided by dopamine concentrations? An SSRI can block out the good feelings of MDMA and inhibit the explosion of serotonin but not block dopamine production.
I pasted your NIH database study link below, and I have added some links and comments above it:
ACUTE Hyperthermia is a symptom of serotonin syndrome last time I checked. see table 1:
http://www.currentpsychiatry.com/images/pdf/CP%200503%20Tables%20and%20Charts/Serotonin/CP503ST1.pdf
Since then, case reports have described serotonin syndrome with many drug combinations, including nonpsychotropics and illicit drugs. Using an irreversible MAOI with a serotonergic agent is the most toxic reported combination, but any drug or combination that increases serotonin can, in theory, cause serotonin syndrome (Table 2). A clinical scale3 is being developed to define and identify this potentially dangerous state, but no consensus has emerged on diagnostic criteria.
Look at the list of drugs here {table 2} and tell me if Effexor or ecstasy {MDMA} are in there.
http://www.currentpsychiatry.com/images/pdf/CP%200503%20Tables%20and%20Charts/Serotonin/CP503ST2.pdf
6. Neither fluoxetine or fluvoxamine altered MDMA-induced ACUTE HYPERTHERMIA. 7. These data demonstrate that fluoxetine produces long-lasting protection against MDMA-induced neurodegeneration, an effect apparently related to the presence of the drug and its active metabolite inhibiting the 5-HT transporter. Fluoxetine does not alter the metabolism of MDMA or its rate of cerebral accumulation.
Effect of GBR 12909 and fluoxetine on the acute and long term changes induced by MDMA ('ecstasy') on the 5-HT and dopamine concentrations in mouse brain.
However, GBR 12909 (10 mg/kg, i.p.) not only failed to prevent the acute effects induced by MDMA (30 mg/kg x 3, i.p.) on dopamine metabolism 30 min later, but in fact potentiated them. The 5-HT uptake inhibitor, fluoxetine (10 mg/kg, i. p.) failed to prevent both the acute and long term dopaminergic deficits.*** so, a dopamine reuptake inhibitor doesn't prevent the effects of MDMA even though MDMA produces dopamine. that was just an interesting thing to find. Prozac does not take care of dopaminergic deficits, so it really doesn't take care of those post ecstasy blues does it? THIS STUDY SAYS PROZAC DOES NOTHING FOR MDMA caused DOPAMINE DAMAGE!****
** By title alone this means nothing because it doesn't relate to serotonin syndrome**Alpha-lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity.
Attenuation of 3,4-methylenedioxymethamphetamine (MDMA) induced neurotoxicity with the serotonin precursors tryptophan and 5-hydroxytryptophan
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7934616
*****we know that tryptophan increases serotonin levels, and it is great if serotonin levels can be increased or stablized because MDMA is neurotoxic!***
The monoamine oxidase-B inhibitor L-deprenyl protects against 3,4-methylenedioxymethamphetamine-induced lipid peroxidation and long-term serotonergic deficits
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7538579
****deprenyl's metabolite is like l or d methamphetamine; i am not sure of the significance of that but it is no wonder it is being studied for meth addiction treatment***
3,4-Methylenedioxymethamphetamine (MDMA)-induced serotonergic neurotoxicity was assessed in the striatum, hippocampus and frontal cortex of rats by using [3H]paroxetine binding to label serotonin (5-HT) uptake sites and 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels as markers of serotonergic function. MDMA (40 mg/kg) induced a significant decrease in both [3H]paroxetine binding Bmax and 5-HT and 5-HIAA levels 7 days after treatment.
***MDMA screws with paroxetine. Okay, that is what I gather.****
The monoamine oxidase-B inhibitor L-deprenyl (2 mg/kg) administered 30 min before MDMA blocked these decreases.
***deprenyl saves serotonin receptors I gather**
MDMA (40 mg/kg) also maximally increased the formation of thiobarbituric acid reactive substances (an indicator of lipid peroxidation) 12 hr after treatment in all three brain regions studied. This increase in malondialdehyde formation was also blocked by pretreatment with L-deprenyl. Tryptophan hydroxylase (TPH) activity was also significantly reduced 18 hr after MDMA. L-Deprenyl reversed this decrease in TPH activity.
*** go deprenyl!***
Another experiment confirmed that a significant fraction of [3H]dopamine uptake into hippocampal synaptosomes was blocked by 500 nM fluoxetine, a selective 5-HT uptake inhibitor.
** i have read that serotonin increase in SSRIs causes dopamine decrease or something-- is that related to this? is that why SSRIs make us apathetic?*****
These data suggest that the deamination by monoamine oxidase-B of excessive dopamine within the 5-HT terminal generates hydrogen peroxide that may lead to membrane lipid peroxidation, and perhaps other oxidative insults, resulting in selective 5-HT terminal degeneration subsequent to MDMA treatment.*** so dopamine rips up the serotonergic areas??? so if MAO-B is inhibited by deprynel than the by-product of MAO-B can not hurt 5-HT terminals??
WHAT DOES THIS SAY ABOUT SEROTONIN SYNDROME??????? NOTHING!!****Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT.
MDMA-induced 5-HT neurotoxicity has been proposed to involve oxidative stress due to increased formation of hydroxyl radicals. Recently, MDMA-induced 5-HT neurotoxicity has been shown to be accompanied by a suppression of behavioral and neurochemical responses to a subsequent injection of MDMA.
*** this is interesting!!! so hypothetically, MDMA and an SSRI can cause 5HT neurotoxicity, but the SSRI that is left working and subsequent doses increase or stabilize 5HT levels.an SSRI supposedly blocks the effects of MDMA. according to the above, when 5-HT is at toxic levels, MDMA can not be felt.
So, in actuality a person on an SSRI and MDMA is really on the threshold of serotonin syndrome. COULD THAT BE MORE TRUE than the idea an SSRI BLOCKS out MDMA as if nothing were taken into the body??!??!?!?****
I think it is obvious here that people see the word "protective", and they think there is my excuse to use the SSRI or ignore the possibility of serotonin syndrome which once again appears in varying degrees from MILD to FATAL.
poster:PsychoSage
thread:332813
URL: http://www.dr-bob.org/babble/20040402/msgs/333594.html