http://www.reddit.com/r/...gNerds/comments/4rw8p5//

This post on Reddit's DrugNerds subreddit really caught all 3 eyes of mine. In this post, a male in his late 20s talks about how he concomitantly uses selegilene (an irreversible MAOI) with frequent (once weakly) high dose (300mg) MDMA for four (or so) weeks on end. He found (in his own subjective experience) that the selegilene decreased the negative side/after-effects associated with high dose MDMA use, which led him to suggest that years' worth of reasoning that taking MAOIs with amphetamines was wrong, and that, instead, the use of MAO-B inhibitors (e.g. selegilene) may in fact be beneficial as it may help reduce hangovers & possible neurotoxicity issues.

I'm not quite sure what in the world to make of this experiment, but would like to report these results to the community at large for public input; I am very interested to hear others' insights regarding this totally taboo drug combo, as well as their own experiences with it (if applicable). He also mentioned that selegilene was mainly an MAO-B inhibitor, which led him to suggest that it wouldn't lead to serotonin syndrome, yet other posts on here have suggested that the use of MAO-A inhibitors may be safe with MDMA. Are they? Could it be that decades' worth of worldwide suspicion regarding this combo was a crock of USDA-grade A BS, or was it just a special case which isn't applicable to most of the psychonautical community at large? I eagerly await and appreciate everyone's input concerning this subject.

Stay well,
Stay safe,
Stay Sane,
Stay,
-God

I'd have to look into the specific claim this person is making (and we would first have to make the leap of faith to believe its true). But no, please don't get the idea that MDMA+MAOIs is safe, many people have died from this combination (at least from MAO-A inhibitors). Just because someone (supposedly) took that combination and didn't die doesn't mean they don't have unnoticed damage, neither that it will continue being safe for them if they keep doing, and neither that others will be just as safe. Also, just because a combination of substances will have beneficial effects in one area doesn't mean they dont have detrimental effects in others.

http://www.ncbi.nlm.nih.gov/pubmed/12603236
http://www.ncbi.nlm.nih.gov/pubmed/21570786
http://jat.oxfordjournal...ontent/35/4/219.full.pdf

I dont have much time now but I think it would be interesting to look into the metabolic pathway of MDMA, affinity of different MAOI subtypes, change in metabolism when enzymes are inhibited, role of CYPs in potential toxicity, genetic variation between different people which may be significant etc.. It's a complex matter that would deserve an in-depth look.

MDMA is a releasing agent of serotonin, MAOIs inhibit the breakdown of serotonin. Combine them and voila, serotonin syndrome. I'm no neuroscientist, but that is logic I'm not going to screw with.

A better way (at least according to popular belief) of averting the MDMA down is to replenish/boost the serotonin levels with 5HTP, though I'm uncertain of the validity of this claim.

In short, synthetic drugs are bad.
Stick to shrooms, peyote and DMT

Found this just now. Only the abstract. Ive read some other stuff before about selegeline having neuroprotective properties when combined with mdma. Ill try and find some papers about it.
Maoi-a and RIMA's are definitely a dangerous combo though


http://www.ncbi.nlm.nih.gov/pubmed/7542394#

And this one;


https://www.google.co.uk...2=TTVfJ2S-Mjf3sPB1umb-9A

So it seems maoi-b and mdma could actually be safer than mdma alone, whereas maoi-a and mdma is very dangerous.

This information kicks some sumo-sized touchis! Keep the studies coming guys! It may just be that the whole taboo against taking MAOIs with MDMA (a very potent MAOI in of itself) was only half-rooted in reality, and may in fact be good for ppl who suffer bad hangovers from that lovey-dovey bullcrap. The redditor who spearheaded this research revolution may have found yet another awesome way to minimize the bad parts of MDMA whilst maximizing the good!

As stated before, selegiline is an MAO-B inhibitor, with negligible activity regarding MAO-A. It may just be that, despite their relative benign-ness with other substances IME, RIMAs such as harmalas (which of course are EXTREMELY and MUCH MORE SO unique than any other MAOI I've ever encountered in my studies & travels, yet still haven't and will not test with MDMA) may just be the bad side of this coin which gave this combo a bad name. Also, the studies endlessness points to seem theoretically correct at best, and horribly convoluted with boatloads of misinformation and background noise (i.e. other drugs/activities which were at play which may have been more toxic towards life than MDMA itself could ever dream of being). Another issue is that most MDMA is complete bull crap, cut to bejeesus and back with God-only-knows what kids will buy and pop by the dozens at rave-themed electronic music "festivals" (read: overly-hedonistic, overly-priced, gigantic drug-doing dens which breed dozens of hundreds of tragically unique drug OD case reports by the day), so how in the hell could we prove that this combination is unilaterally unsafe for all and any persons and MAOIs (yes, each drug is just as unique as the person who dies doing it as well as the manner (read: TRIP) in which they die from doing it). I am interested in seeing the possible utilization of selective MAO-B inhibitors, such as selegilene & Cat's Claw, after MDMA use/abuse, as I would be willing to hypothesize that, based on equally credible documents currently presented in this thread, that these drugs may be of quite some use in combating post-roll fatigue and depression, the devastating effects of which (as in my case) could last for upwards of a week post-use (and yes, I do indeed always test each and every batch of moonrocks with marquis, mandelin, and mecke reagents everytime, so I have a good idea of just what kinda chemical i'm dealing with). I would like to see more studies concerning the interaction of amphetamines (which are in fact MAOIs as well) with other classes/kinds of MAOIs in humans as, despite how potentially harmful & unethical this science seems, it is still science; very interesting science at that; and like any & all other cool and interesting sciences which pique my fancies, it must be further researched and further pursued until some kinda Frankenstein-like Monster comes out of it and proceeds to haunt me until the day I die.

Please keep this rockin' research a rolling,
-God/Cave Johnson's re-incarnate

When one takes MDMA it basically pries open the reuptake receptor in the serotonin cell. Other neurotransmitters get taken up through this SERT pathway where they are broken down by MAO-B into oxides that cause damage to the cell, hence neurotoxicity.

By taking an inhibitor of MAO-B, it helps prevent this oxidation process, though having the wrong neurotransmitters in serotonin cells can also damage the cell, which is why an SSRI taken ***POST MDMA***, which prevents other NT's from getting in the cell in the first place by blocking the reuptake receptor, is a moar effective measure against neurotoxicity.

More information on this mechanism is available here.

The main source of this information is one of the studies ijahdan linked above. Namely:

Sprague and Nichols, “Inhibition of MAO-B protects against MDMA-induced neurotoxicity in the striatum”, Psychopharmacology (Berl), 1995; 118(3):357-359.

Attached for the readers convenience.

I can't help but think this is a dangerous topic and subject maybe left for members only or actual psychiatrists to talk about.
I see the subject and I just see an accident waiting to happen.

Not trying to be a ninny.. just if anyone misunderstands the information presented here it really could be fatal..


My 2 cents.
Ess

Two questions: Firstly, does MAOI-B taken before MDMA have the potential to cause hyperserotonimia, or will it simply lessen the affects of the MDMA (as the link suggests). Secondly, what would a MAOI-A like harmaline do differently, before or after having consumed MDMA, in terms of the neurological affects, and how does this differ from the affects of an irreversible MAOI-A.

Sorry, I know this probably does not need to be said, and I'm sure everybody understands this, but I think people have an irrational fear of synthetic compounds and chemistry in general, and statements such as these fuel chemophobia, even if such statements were made light-heartedly.

Synthetic drugs are not "bad", this is a fallacy.

The notion the a compound can be "good" or "bad" is a fallacy, the compound is inanimate.

Psilocybe fungi, mescaline cacti, and dimethyltryptamine are pharmocologically safe, they are plant derived, they structurally resemble our higher neurotransmitters and have long history of human use, these are all positive features, and prove the general ability to safely consume these compounds...

However this is no reason to dismiss synthetic compounds, or classify them as "bad"

Natural compounds can be just as "bad" or as "good" as synthetic compounds...morphine and codeine are natural, and in terms of negative impact, are terrible drugs, most opioid dependence starts with codeine or morphine pills, two fully natural plant compounds...

The same responsibility should go into using any compound, plant derived or synthetic, either can be equally dangerous and requires the same degree of precaution and care. A compound having its source in a plant or in the lab really makes no difference.

Sorry this was a little off topic.

-eg

Excess serotonin should not be an issue when pre dosing with an MAO-B inhibitor, as MAO-A is responsible for serotonin breakdown. MAO-B mostly focuses on phenethlyamine compounds. I'm less well versed in the pharmacokinetics of MAO-B, but from what I understand, pre-dosing an inhibitor of MAO-B would prevent breakdown of the MDMA itself as well as allow for excess build-up of other phenethylamine neurotransmitters such as dopamine. I wouldn't suggest it, I could be wrong about how that all works though. Just like using an SSRI, best results for preventing neurotoxicity would be obtained by dosing the MAO-B inhibitor during the comedown of the MDMA.

An MAO-A inhibitor is different, it prevents the breakdown of serotonin, so pre or post dosing both risk serotonin syndrome.

While a reversible inhibitor of MAO-A or MAO-B clears the system quickly and may not cause complete inhibition, allowing for normal MAO function within a few days, a non-reversible inhibitor will inhibit MAO function fully for approximately 2 weeks. This is why there are special dietary recommendations and other considerations for non-reversible MAOI's.

I would strongly discourage the use of non-reversible MAOI's in conjunction with MDMA or other amphetamines within any context.

I understand what you're getting at, but the unfortunate truth is that your average MDMA user hasn't a clue what he/she is ingesting. They may believe it to be pure LSD, or pure MDMA, but they don't know. Synthetic drugs have a great potential to be very bad. There have been many fatal overdoses of people using LSD, when in fact, unbeknownst to them, it was 25I or one the DOx. 5 tabs of LSD and 5 tabs of 25I are very different things. I personally will be steering far away from anything that isn't a plant, made by me or tested for purity.

This is a pretty good strategy in my opinion. Reagent tests are not perfect and you ideally should use several kits for accuracy. Buying drugs is a very risky business because the desired products and their various substitutes can be made so visually similar, plus it is conceivable that sellers can do clever things to help make the substance appear to be correct, on at least a few reagent tests.

Anyway, on the main topic:

The risks being taken for what appears to be small benefit (avoiding MDMA hangovers) doesn't make that much sense to me; it seems that there are a lot of details that might complicate such an undertaking (details that an average party-goer is sure to slip up and/or forget), and getting details wrong poses a serious, well-understood risk of brain damage or death. Not a good bargain!

In general, taking one drug to counter the comedown of another drug seems to be a short-sighted strategy that can burden the body more than either chemical alone. In my view, if you have a hangover of any kind, it's better to face the music and let the body do it's natural thing to recover, even if that means you feel crummy. Drink water, sleep in, do whatever; just don't constantly run the circuits upstairs on overdrive just for your immediate comfort.

Just because he hasn't felt a hangover doesn't mean he's fine; his reasoning makes me worried. There is a possibility that the article author has already injured themselves and they are not aware of it, but sadly we can't know for sure. Brain damage isn't something that you can readily feel like a stomach ache!

isn't tumeric an MAO-B inhibitor?

Turmeric is an inhibitor of both MAO-A and MAO-B at very high doses.

Attached:
Yu, Z. F., L. D. Kong, and Y. Chen. "Antidepressant activity of aqueous extracts of Curcuma longa in mice." Journal of Ethnopharmacology 83.1 (2002): 161-165.

Garlic (or garlic extract) I believe is a good inhibitor of MAO-B

In doing some further research on this, it appears the main danger of predosing an MAO-B inhibitor before taking MDMA is going to be excessive build up of catecholamine neurotransmitters. While excess dopamine isn't too much of a concern (and would in part help explain the positive/mood boost effects the author of the reddit thread in the OP describes), buildup of noradrenergic neurotransmitters is a serious concern and can lead to hypertensive crisis and even death. This is why tyramine containing foods and amphetamines are contraindicated with MAOI's, as both can lead to noradrenergic toxicity.

Another possible issue with MAO-B inhibitors is that they can prevent the breakdown of MDMA and it's metabolites, which themselves may be taken up through the SERT pathway and contribute to neurotoxicity within the serotonin cell. While in one respect MAO-B inhibitors may help to prevent neurotoxicity, in another respect it is possible they may help to compound it.

We also know very little about MDMA and it's metabolites in relation to CYP enzyme metabolism and preventing normal breakdown of these compounds via MAO-B inhibitors could potentially effect these mechanisms as well.

So while that's all well and good, that leads us to heart of the matter. How does one best prevent the neurotoxic effects of MDMA?

As alluded to previously, MAO-B inhibitors taken post MDMA can be helpful in this regard, however it appears an SSRI is significantly more effective at preventing MDMA induced neurotoxicity. There is a catch-22 here however, while taking an SSRI prior to MDMA is most effective at preventing neurotoxicity, it is also reported to significantly dampen the effects. Taking an SSRI at 6 hours after MDMA ingestion did have detectable effects in preventing neurotoxicity, but only slightly. Taking an SSRI at 12 hours after MDMA ingestion did not have a detectable effect in preventing neurotoxicity. So there is a short window in which dosing an SSRI is effective. It should also be noted this research was done specifically with Prozac (fluoxetine), so it may not be generally applicable to other SSRI's, and pre-dosing an SSRI before MDMA may still potentially risk serotonin syndrome.

It is also important to note most of the research regarding SSRI's in preventing MDMA neurotoxicity has only been done in animals and may not be applicable to humans.

So, with that foundation under our belt, what are some good short acting SSRI's and reversible inhibitors of MAO-B?

Turns out many of the kavalactones in Kava Kava (Piper methysticum) appear to be reversible inhibitors of MAO-B with short half lives. I would suggest further research on the other properties of these compounds before diving in, but this looks like a promising option. Again, noting that an SSRI is more effective than an MAO-B inhibitor for preventing MDMA neurotoxicity.

The one I mainly work with post MDMA is Kanna (Sceletium tortuosum). Many of the compounds in Kanna have mild SSRI effects and short half lives making it an ideal alternative to pharmacuetical SSRI's for blocking the SERT pathway and preventing neurotoxicity. It's not very tasty on it's own, but a couple grams of Kanna with a couple grams of licorice root make a fine comedown tea.

Another short acting natural SSRI worth looking into is an old favorite of this forum that is near and dear to all our hearts, our very own THH (Tetrahydroharmine). There is a lack of information on exactly how effective THH is as an SSRI, but from what I can tell it should be effective enough for our purposes, and it has a fairly short half life, making it a great candidate. Now that we have a good conversion tek on the forum, this is certainly an area worthy of further research.

One last herbal supplement that deserves honorable mention is St. Johns Wort (Hypericum perforatum). This herb is a non-selective monoamine reuptake inhibitor with a long history of post MDMA use amongst user communities. There are both pros and cons to non-selective reuptake inhibition, and in general a more specific SSRI is preferred, but just know this is another option that can assist in preventing neurotoxic effects from MDMA.

Note: Do not combine SSRI's and MAOI's. Do not take SSRI's or MAOI's with St. Johns Wort. Pick one of the above options, do not mix them. Allow at least 3 days between taking any of the above herbs and any other form of SSRI or MAOI (including harmalas).

A note on 5-HTP: 5-Hydroxytryptophan is a precursor for serotonin that will give a short term temporary serotonin boost. This means it's most effective to take while you are on MDMA to get a little extra kick out of your roll, but it's not very effective as a post MDMA supplement, because the serotonin boost is so short lived. Better options for longterm rebuilding of serotonin levels post MDMA are supplements that will upregulate your serotonin receptors such as Ayahausca/Harmalas and St. John's Wort (Remember to wait a few days after your MDMA session before beginning to take these substances, and don't mix them).

Don't forget to dose heavy on the vitamins and antioxidants before, during, and after your sessions.

And of course, remember to
TEST YOUR DRUGS!

Rave Safe,
-PLURR


MAO-B Inhibitors and MDMA
CNS stimulants with MAOIs
Markowitz, J. S., S. D. Morrison, and C. Lindsay DeVane. "Drug interactions with psychostimulants." International clinical psychopharmacology 14.1 (1999): 1-18. * Attached

MDMA and CYP Enzymes
Enzyme CYP2D6 and MDMA Pharmacology

MDMA and SSRI's
This is Your Brain on Ecstasy ^ Really!: An MDMA Neurochemistry Slideshow
McCANN, UNA D., and GEORGE A. RICAURTE. "Reinforcing subjective effects of (+/-) 3, 4-methylenedioxymethamphetamine (" ecstasy" ) may be separable from its neurotoxic actions: clinical eRemember to vidence." Journal of Clinical Psychopharmacology 13.3 (1993): 214-217. * Attached
Sanchez, V., et al. "The mechanisms involved in the long‐lasting neuroprotective effect of fluoxetine against MDMA (‘ecstasy’)‐induced degeneration of 5‐HT nerve endings in rat brain." British journal of pharmacology 134.1 (2001): 46-57.

Kava
Uebelhack, R., L. Franke, and H-J. Schewe. "Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)." Pharmacopsychiatry 31.05 (1998 ): 187-192. * Attached

Kanna
Gericke, N., and A. M. Viljoen. "Sceletium—a review update." Journal of ethnopharmacology 119.3 (2008 ): 653-663. * Attached
Harvey, Alan L., et al. "Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids." Journal of ethnopharmacology 137.3 (2011): 1124-1129

THH
Callaway, James C., et al. "Pharmacokinetics of Hoasca alkaloids in healthy humans." Journal of ethnopharmacology 65.3 (1999): 243-256

St. Johns Wort
Nathan, Pradeep J. "Hypericum perforatum (St John's Wort): a non-selective reuptake inhibitor? A review of the recent advances in its pharmacology." Journal of Psychopharmacology 15.1 (2001): 47-54. * Attached

Fairly high doses of garlic extract taken over longer periods of time inhibit both MAO-A and MAO-B.

Dhingra, Dinesh, and Vaibhav Kumar. "Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of garlic extract in mice." Indian journal of pharmacology 40.4 (2008 ): 175.

Dreamer042 wrote:

"Another short acting natural SSRI worth looking into is an old favorite of this forum that is near and dear to all our hearts, our very own THH (Tetrahydroharmine). There is a lack of information on exactly how effective THH is as an SSRI, but from what I can tell it should be effective enough for our purposes, and it has a fairly short half life, making it a great candidate. Now that we have a good conversion tek on the forum, this is certainly an area worthy of further research."

This made me think of a couple of things, firstly, where can I fimd this conversion tek? I looked in the harmala section and the wiki but there only seems to be discussion of various methods, not a solid tek for the process.

Secondly, assuming the conversion is not 100% perfect, wouldn't the presence of unconverted harmaline be a risk?

Not planning to try any mdma combos anyway, hardly take it anymore, few times a year at most, but I would like to convert some rue extract to thh as it just doesnt have that caapi magic.

Hordenine is a fairly well studied MAO-B Inhibitor that accours in many plants:
https://en.wikipedia.org/wiki/Hordenine

Unfortunately the plants that contain hordenine also contain other phenethylamines which could be dangerous. Fortunately the 99% pure HCL salt can be found online as a supplement for bodybuilding.

I believe that peyote and san Pedro contain hordenine. We all know about the phenethylamines they contain, but i don't think there's a real risk there.