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Discussion => Drug safety => Topic started by: HenryC0833 on August 24, 2013, 04:20 pm

Title: MDMA off switch
Post by: HenryC0833 on August 24, 2013, 04:20 pm
MDMA needs an off switch.  The adrenergic stimulation lasts much longer than the serotonergic or dopaminergic, resulting in lingering side effects and maybe a hangover.  Ideally, we would like to turn the MDMA "off" at that point to block the adrenergic effects.  Also if we could block NMDA receptor stimulation, so much the better.  For the most part, I "turn it off" by having a nice big breakfast.  I mean, isn't that why God invented Denny's? 

But with regard to pharmacological measures, what do you think would be best?

This is not exactly the same as asking about serotonin repletion, which is a subtly different topic.

I've heard of the following being advocated:

1.  SSRI's.  Some lab evidence of efficacy, but I worry about "dirty" chemicals that have some SNRI activity.
2.  Benzo's.  Interesting drug.  They do have an effect on central alpha receptors, seems like the lab data suggests the are central alpha stimulants?  But some central alpha stimulants (eg Clonidine) reduce peripheral adrenergic activity.  Benzo's are known to reduce peripheral adrenergic activity and is the recommended choice for amphetamine overdose.  Unclear to me the effect on NMDA receptors.

I wonder about the following:
1.  Barbiturates (assuming they can be found) which I believe are NMDA antagonists.
2.  Alcohol, which is an NMDA antagonist.
3.  Seroquel, which is pretty much the all-purpose "off switch" for psychedelics, of which MDMA is an example, in my opinion.  Seroquel does have activity at the NMDA receptor but it's not totally clear to me what it's doing there.  It seems to reverse the effects of NMDA agonists in animal studies, which is probably not precisely what we want, although in itself that statement doesn't tell the whole story.  It is a potent peripheral alpha blocker.  It has mood stabilizing, anti-anxiety and sedative properties. 
4.  Other specific NMDA antagonists, eg Ketamine.   (But NOT tramadol, which has been associated with serotonin syndrome.)

I am actually the most interested in Seroquel, which arguably should be included in the stash of any intrepid psychonaut. 

Anybody tried it?  What do you think?

Title: Re: MDMA off switch
Post by: Ballzinator on August 24, 2013, 05:53 pm
Barbiturates are positive allosteric GABA-A modulators, just like benzos.
Alcohol is an α7-nAChRs agonist, positive allosteric GABA modulator, 5-HT3 agonist, NMDA antagonist, AMPA antagonist, KARs antagonist, glycine agonist, an inhibitor of potassium, sodium and calcium ion channels, as well as adenosine reuptake.

Alcohol is out of the question because its shitty pharmacology makes it unpredictable.
Benzos and barbs will calm you down and they work well for MDMA comedowns and hangovers.
I have never heard of MDMA stimulating NMDA receptors and I can't find anything about it online so NMDA antagonists are probably not the best idea for MDMA hangovers.
Seroquel is also an antagonist of the 5-HT1A, 5-HT2C, 5-HT7, D1, D2, D3 and D4 receptors, which is probably not too helpful when coming down from a powerful SNDRI like MDMA.

If it's the reduction of adrenergic activity you're after, why not simply try α- and/or β-blockers?
Title: Re: MDMA off switch
Post by: zvp1014 on August 24, 2013, 06:28 pm
Perhaps it's a good idea if you're within walking distance of one, but Denny's sounds like an awful idea if you have to drive.
Title: Re: MDMA off switch
Post by: HenryC0833 on August 24, 2013, 08:54 pm
Eh never liked beta blockers in amphetamine overdose because of risk of peripheral vasoconstriction.  I know it's not the same but still. 

Coulda swore I read somewhere that the theory on MDMA neurotoxicity was due to NMDA receptor stimulation, but maybe that was just speculation or sumpin
Title: Re: MDMA off switch
Post by: HenryC0833 on August 24, 2013, 08:57 pm
I see your point tho on using seroquel in a serotonin depleted state.  Not exactly the same as using it to abort say an LSD trip
Title: Re: MDMA off switch
Post by: slirp on August 26, 2013, 02:14 am
I've never seen any data on adrenergic release from MDMA.  Does anyone have a link?  I'm really surprised to hear that MDMA causes an increase in (nor-)epinerpherine that lasts longer than the serotonin/dopamine increase.  Certainly interesting.

To sleep I just take a benzo such as Valium and go to sleep but then again I usually don't do that until long after taking the MDMA.
Title: Re: MDMA off switch
Post by: Dingo Ate My Drugs on August 26, 2013, 07:41 am
This is the case with most drugs.
The euphoria ends before the excessive stimulation does.
Just a part of the drug. Use a benzo after the drug to help sleep.