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
References
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.
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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.
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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.
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Kanna
Gericke, N., and A. M. Viljoen. "Sceletium—a review update." Journal of ethnopharmacology 119.3 (2008 ): 653-663.
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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.
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