St Johns Wort and MDMA neuroprotection

[MakhnovistMushroom]

Fluoxetine (Prozac) taken ~6 hours after MDMA has been demonstrated to prevent the neurotoxic effects of the MDMA, due to its SSRI properties.
http://www.mdma.net/protect/prozac.html

Unfortunately Prozac is hard to get hold of. However, the herb St Johns Wort (available at health food shops) has (weaker) SSRI properties. Some questions:

Would this inhibit (or at least help reduce) neurotoxicity in a similar way to Prozac? A double dose of Prozac is recomended, how would one go about aproximating this with St Johns Wort? Prozac stays in the body for a long time (~half life of 7 days), would one need to redose St Johns Wort to approximate Prozac's effects, and if so how much and for how long?

Anything related to the use of St Johns Wort as neuroprotective appreciated. Cheers.

 

[nuke]

I have a feeling the protection it would lend would either be marginal or reduce the effects of the drug, or both.

The best way to prevent against neurotoxicity while not modifying the effects is probably with either MAO-B inhibitors or antioxidants. The former may not be safe (although everyone who has tried it so far has survived).

I've been recommending a high dose of idebenone (200mg-500mg) 2 hours before and then 1 hour in recently, due to idebenone's ability to easily cross the blood brain barrier, it's high functionality as an antioxidant and its very long half-life.

 

[Hammilton]

although everyone who has tried it so far has survived

At least as far as we know. I feel fairly certain someone has combined an MAOI and MDMA and not lived to tell us about it by now.

With idebenone, at least you don't have to worry about dying, but unless it's blocking monoamine oxidase, I don't know how useful it'll be. I haven't looked yet, but how does it accomplish it's antioxidant function?

Hyperforin is believed to be the primary active constituent responsible for the antidepressant and anxiolytic effects of the extracts of St. John's Wort.[6] Hyperforin has been shown to be a potent reuptake inhibitor of serotonin, norepinephrine, dopamine, GABA and glutamate and exerts these effects by to and activating the transient receptor potential ion channel TRPC6.[7][8] Activation of TRPC6 induces the entry of sodium and calcium into the cell which explains the inhibition of reuptake.[8]

Hyperforin is also thought to be responsible for the induction of the cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor (PXR).[9]

Hypericin is a red-coloured anthraquinone-derivative, which is together with Hyperforin one of the principal active constituents of Hypericum (Saint John's wort). Hypericin is believed to act as an antibiotic and non-specific kinase inhibitor. Hypericin may inhibit the action of the enzyme dopamine β-hydroxylase, leading to increased dopamine levels, although thus possibly decreasing norepinephrine and epinephrine.

I haven't looked up numbers, so I wonder how potent the former compound actually is, or how much is present, but it should be effective. That they claim it inhibits the reuptake of virtually everything is worrisome. 5HT, NE, DA, GABA, and Glutamate? Wow.

That it does so by TRPV6 agonism makes me wonder how effective it would be compared to Fluoxetine.

I would imagine that something actually blocking SERT would be preferable.

Mesembrine is an equally available alternative that is really an SSRI, and a very potent one.

That the latter compound blocks dopamine beta-hydroxylase is interesting. It would be really interesting to know how it effects the couse of stimulant psychosis. It might be useful for standard stimulant abusers (not serotonergic stimulants).

 

[nuke]

At least as far as we know. I feel fairly certain someone has combined an MAOI and MDMA and not lived to tell us about it by now.

With idebenone, at least you don't have to worry about dying, but unless it's blocking monoamine oxidase, I don't know how useful it'll be. I haven't looked yet, but how does it accomplish it's antioxidant function?

Probably the same as ubiquinone (which promotes regular mitochondrial function), although I'm not sure ubiquinone is completely characterized as to its antioxidant mechanism. Ubiquinone does react very quickly with O2·−/HOO·, effectively scavenging the oxidants.

Since the products of monoamine oxidase that mediate MDMA-induced neurotoxicity and cause neurons to undergo apoptosis via caspase-3 are O2·−/HOO·/NO·, it would theoretically be very effective. It should also be noted that monoamine oxidase lies within the outer mitochondrial membrane.

Antioxidant properties of 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone (idebenone).

Mordente A, Martorana GE, Minotti G, Giardina B.
Institute of Biological Chemistry, Catholic University School of Medicine, Rome, Italy. [email protected]

Idebenone [2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone] is a synthetic analogue of coenzyme Q that is currently employed in the treatment of vascular and degenerative diseases of the central nervous system. There is some evidence to suggest that idebenone might function as an antioxidant; however, it has not been demonstrated whether this function pertains to the quinone or hydroquinone form of idebenone. Here we demonstrate that idebenone can scavenge a variety of free radical species, including organic radicals such as 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and diphenylpicrylhydrazyl, peroxyl and tyrosyl radicals, and peroxynitrite. Idebenone can also redox couple with hypervalent species of Mb or Hb, thus preventing lipid peroxidation promoted by these species. Likewise, idebenone inhibits microsomal lipid peroxidation induced by ADP-iron complexes or organic hydroperoxides. In so doing, idebenone prevents the destruction of cytochrome P450, which otherwise would accompany lipid peroxidation. Irrespective of the experimental system under investigation, idebenone functions by virtue of the electron-donating properties of the hydroquinone form. Redox coupling of this hydroquinone with free radicals generates the quinone compound, which per se lacks antioxidant activity. In many experiments, the antioxidant effects of idebenone become appreciable at approximately 2 microM, which is well in the range of plasma levels attainable in patients given oral doses of this drug. Moreover, comparative experiments have shown that the antioxidant efficiency of idebenone varies from no less than 50% to slightly more than 100% of that of vitamin E or Trolox. We would therefore propose that the neuroprotective effects of idebenone can be attributed, at least in part, to its ability to function as an antioxidant, involving redox cycling between hydroquinone and quinone.

http://www.ncbi.nlm.nih.gov/pubmed/9477226

Though some reviews say it may not be helpful: http://www.ncbi.nlm.nih.gov/pubmed/12709577

But for the most part it's been shown to be a useful, strong antioxidant:
http://www.ncbi.nlm.nih.gov/pubmed/9890635
http://www.ncbi.nlm.nih.gov/pubmed/12161253
http://www.ncbi.nlm.nih.gov/pubmed/9840428
http://www.ncbi.nlm.nih.gov/pubmed/9618276

 

[MakhnovistMushroom]

Thanks for the replies.

I have a feeling the protection it would lend would either be marginal or reduce the effects of the drug, or both.

Well, the idea would be to take the SSRI just as the effects of the MDMA were wearing off. Thats how the Prozac which proved effective in rats was administered. Why do you feel the protection would be marginal?

I've been recommending a high dose of idebenone (200mg-500mg) 2 hours before and then 1 hour in recently, due to idebenone's ability to easily cross the blood brain barrier, it's high functionality as an antioxidant and its very long half-life.

Ok. Antioxidants should obviously be taken too. Though from what I've read their protection isn't as good as Prozac. Would Idebendone be much better than 1000mg vit C (redosed as needed) or other cheap antioxidant?

Mesembrine is an equally available alternative that is really an SSRI, and a very potent one.

Cheers. What sort of dose/redose would aproximate a double dose of Prozac?

 

[MakhnovistMushroom]

Cheers rocknroll. Dosing SSRI's 3 hours in would cut the effects rather short, no? Can you link the studies which show that 6hrs in only partialy blocks (and that 3 completely does so)?

Which do people think would be more effective, Chlorpheniramine or Mesembrine? And if Mesembrine, what sort of dose/redose?

 

[DaftPunkFan]

I would highly recommend against using SJW has a neuroprotectant. SJW exerts its reuptake inhibition in a much different way than traditional SSRIs and it's far, far weaker at doing so. It's not even a substrate for SERT.

You can, however, use the antihistamine chlorpheniramine to protect against the damage. Chlorpheniramine is a potent and long-lasting (24h+) serotonin reuptake inhibitor. It was shown in rat studies to completely block the damage induced by MDMA just like the SSRIs. Better yet, it's available almost everywhere over-the-counter for cheap. I'm not exactly sure what dose to recommend you but I'm guessing somewhere around 50-100 mg. Here's some more information:

• http://en.wikipedia.org/wiki/User:Rocknroll714/chlorpheniramine
• http://www.ncbi.nlm.nih.gov/pubmed/10420168

Also I'd recommend you dose 3 hours in as opposed to 6 hours. In other studies it has been shown that dosing 3 hours in completely blocks the damage, whereas dosing 6 hours in only partially blocks it.

Wow, this is very good information. Would you recommend just using Chlorpheniramine after MDMA, or possibly complementing it with something else to help with the MDMA damamge?

And you said you weren't sure about a good dose, but 50-100mg is a good guess?

 

[Hammilton]

If you combine it you'll probably block the effects.

 

[DaftPunkFan]

Since rat studies have shown that it fully blocks the neurotoxicity 3-4 hours in I'd feel pretty confident that taking a good sized dose after rolling would be sufficient for full protection. If you're paranoid like I am though you could take some antioxidants in conjunction to ensure even greater protection. As for dose, 50-100 mg was a mildly educated but basically complete guess. I'd suggest looking into it a bit more to validate it, which is something I've been meaning to do actually...

Alright cool, sounds like a pretty wise thing to take after rolling. Has anyone actually used this like 3-4 hours into a roll though? Do you notice a significantly smoother comedown/ day after rolling? I'm curious to see what people have experienced....

 

[melange]

neuroprotection vs. possible case of serotonin syndrome?




If I was taking mdma, I wouldn't be thinking about neuroprotection.


I agree with nuke, as in antioxidants is the way you should go

 

[andreas]

This should cover most neuron- protection questions and MDMA


http://www.erowid.org/chemicals/mdma/mdma_article3.shtml

 

[slowboy]

St John's Wort, like some SSRIs, takes about two weeks to kick in. I doubt if taking even a large dose would do anything in the short term other than invoke mild nausea. Having said that I've been taking SJW for about six months and it really does work for me as an anti-depressant/anxiolytic with no apparent side effects. I have no experience of MDMA but if your system is already "topped up" with SJW it may be possible to take a large dose after taking MDMA to counter negative effects. Whether this would actually work or not, or how sensible it would be, I have no idea but it would probably be preferable to taking a large dose of Prozac or something similar.

 

[lenses]

IME SJW quicks in very quickly, perhaps... lets say.... 8 hours after a dose.

I would wait until i'm completely done rolling to dose the SJW. Should be effective...

If your brain isn't too HIT by drugs (ie:healthy) , a once in a while dose of MDMA shouldn't effect it too badly . I believe that MDMA damage builds up the closer your dosing is. The brain has some built in protection against MDMA damage if you're healthy...

Pure molly is very benign to me in doses under 250mgs.

Cannabis is quite neuroprotective as well.

I would recommend the SJW though, I was quite surprised by its effectiveness.

-lenses

 

[Phoenix123]

I'm going to go ahead and give this a big bump.

I understand that, as an SSRI, it may be helpful to take at the end of an MDMA experience. However, what about if it is taken approximately 24 hours beforehand? I have been prescribed it and have been taking it daily for 6 days. My last dose was at 7:30 AM and I want to roll tomorrow night. The dose I took this morning was 8 mg, extended release.

 

[atara]

SJW has MAOI properties, doesn't it? Sounds like a plain awful idea.

Plus an SSRI before MDMA will abolish the effects.

St John's Wort, like some SSRIs, takes about two weeks to kick in. I doubt if taking even a large dose would do anything in the short term other than invoke mild nausea. Having said that I've been taking SJW for about six months and it really does work for me as an anti-depressant/anxiolytic with no apparent side effects. I have no experience of MDMA but if your system is already "topped up" with SJW it may be possible to take a large dose after taking MDMA to counter negative effects. Whether this would actually work or not, or how sensible it would be, I have no idea but it would probably be preferable to taking a large dose of Prozac or something similar.

Wherever this conception arose, it's not very relevant. An SSRI taken after MDMA will inhibit the SERT, even if it doesn't cause any antidepressant effect.

 

[asecin]

I have a feeling the protection it would lend would either be marginal or reduce the effects of the drug, or both.

The best way to prevent against neurotoxicity while not modifying the effects is probably with either MAO-B inhibitors or antioxidants. The former may not be safe (although everyone who has tried it so far has survived).

I've been recommending a high dose of idebenone (200mg-500mg) 2 hours before and then 1 hour in recently, due to idebenone's ability to easily cross the blood brain barrier, it's high functionality as an antioxidant and its very long half-life.

idebenone ? how can you recomend it to people ? its still not comercialy available and its in experimental phases. did you even try it yourself ?

 

[nuke]

Yes, I have, and other people I know have as well. It is commercially available.

 

[chantho]

It hasn't even really been proven that MDMA causes neurotoxicity. All the studies show is that in RATS the MDMA that metabolizes into HHMA and HMMA then MAY release free radicals when they metabolize. But rats metabolize these by glucoronidation and humans by sulfation. the ratio for humans is 3.1 HMMA-Sul to 1.8 HMMA-Glu. If you are still worried then dont do the drug or look up some neuroantioxidants. Ive even found research that proves mary jane is a good neuroantioxidant haha. Journal Article : Xenobiotica, March 2008; 38 (3): p. 314-324 "Urinary Excretion of the main metabolites of 3, 4-methylenedioxymethamphetamine (MDMA), including the sulfate and glucorinide of 4-hydroxy-3-methoxymethamphetamine (HMMA), in humans and rats" cheers guys!

 

[MeDieViL]

It hasn't even really been proven that MDMA causes neurotoxicity. All the studies show is that in RATS the MDMA that metabolizes into HHMA and HMMA then MAY release free radicals when they metabolize. But rats metabolize these by glucoronidation and humans by sulfation. the ratio for humans is 3.1 HMMA-Sul to 1.8 HMMA-Glu. If you are still worried then dont do the drug or look up some neuroantioxidants. Ive even found research that proves mary jane is a good neuroantioxidant haha. Journal Article : Xenobiotica, March 2008; 38 (3): p. 314-324 "Urinary Excretion of the main metabolites of 3, 4-methylenedioxymethamphetamine (MDMA), including the sulfate and glucorinide of 4-hydroxy-3-methoxymethamphetamine (HMMA), in humans and rats" cheers guys!

Some neurotoxic damage has been observed in humans:

Br J Psychiatry. 2008 Oct;193(4):289-96.
Neurotoxic effects of ecstasy on the thalamus.
de Win MM, Jager G, Booij J, Reneman L, Schilt T, Lavini C, Olabarriaga SD, Ramsey NF, Heeten GJ, van den Brink W.
The most interesting finding is that different imaging techniques all showed a specific effect of ecstasy on the thalamus. Even after adjustment for amphetamine, cocaine, cannabis and other relevant potential confounders, a significant effect of ecstasy, and no effects of any of the other drugs, was found on [123I]β-CIT binding (reduced), fractional anisotropy (reduced) and rrCBV (increased) in the thalamus. As [123I]β-CIT SPECT was previously validated to assess in vivo binding to serotonin transporters, the finding of decreased [123I]β-CIT binding probably reflects lower serotonin transporter densities in ecstasy users. Moreover, the thalamus is a serotonin transporter-rich area and previous studies showed that [123I]β-CIT binding in the thalamus is mainly related to transporter binding, although the thalamus also contains noradrenaline transporters. Diffusion tensor imaging measures diffusional motion of water molecules in the brain which is normally restricted in amplitude and direction by cellular structures such as axons. When axons are damaged, extracellular water content increases and fractional anisotropy decreases. Therefore, it is likely that the observed decreased fractional anisotropy is related to ecstasy-induced axonal injury.

Brain. 2008 Nov;131(Pt 11):2936-45. Epub 2008 Oct 7.
Sustained effects of ecstasy on the human brain: a prospective neuroimaging study in novel users.
de Win MM, Jager G, Booij J, Reneman L, Schilt T, Lavini C, Olabarriaga SD, den Heeten GJ, van den Brink W.
Decreased FA and increased ADC in the thalamus may reflect ecstasy-induced axonal damage, because axonal cell membranes are known to be responsible for most of the restriction of water diffusion and axonal damage lead to decreased FA and increased ADC. This finding of ecstasy-induced brain pathology in the thalamus corroborates findings from previous studies showing decreased thalamic SERT densities in (heavy) ecstasy users, most probably reflecting damage to terminals of serotonergic axons...As the thalamus is important for neurocognitive processes, one can speculate that ecstasy-induced thalamic damage is (partly) responsible for decreased verbal memory performance frequently reported in heavy ecstasy users and recently also shown in the current prospective cohort of low-dose ecstasy users (Schilt et al., 2007).

 

[chantho]

Some neurotoxic damage has been observed in humans:

these are all signs of serotonin depletion (at least Im pretty sure thats what your articles say) and while you experience a depletion in baseline serotonin after you do the drug (thats the NATURE of the drug) it was shown through the imaging technique PET (positron emission tomography) that after 20 weeks of discontinued MDMA use serotonin values ( and the associated axons) were recovering. That is why so many people who take MDMA wait like 4 months until doing it again. You can weather this by looking for good stuff in what you eat or taking some amino acid supplements.