Interaction between 5-MeO-DMT and MDMA

[WSH]

5-MeO-DMT is known to cause both very postive effects and also very negative effects (e.g. racing heart, trouble breathing, panic attacks).

I've read that the combination with MDMA does away with these negative effects.

Here are a couple of reports that I've found:

"The MDMA seemed to completely do away with the terror that MeO can sometimes cause... the combination seems to bring out the best of both and combine them into a very nice whole"

"We began with just a tiny eyeballed hit, maybe 5mgs at the most. As soon as I blew out my hit I felt an instant RELAXATION, totally opposite of my 5-MeO trips alone. My thought process nearly stopped and I felt GOOD. Really, really good, like the best I've ever felt. There were no side effects! No racing heart, no problems breathing, just a mellow yet intense bliss"

It is known 5-MeO-DMT is a potent 5-HT1a agonist (~8nM; serotonin: 1.6nM) and 5-MeO-DMT also induces stimulus control via 5-HT1A receptors:

The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors.

In rats trained with 5-MeO-DMT, pindolol and WAY-100635 both produced a significant degree of antagonism of stimulus control

MDMA increases serotonin release and is an antidepressant and anxiolytic (I'm talking about acute effects, not the famous hangover)

5-HT1a autoreceptors decrease serotonin release and therefore they increase depression and panic.

My theory is that the negative 5-MeO-DMT effects are caused by the reduction of serotonin release because of 5-HT1a autoreceptor activation. The MDMA-induced increase of serotonin release cancels out 5-MeO-DMT's decrease, that's why there were no negative effects. 5-MeO-DMT then selectively stimulates postsynaptic 5-HT1a receptors, which would explain the positive effects.

Any comments?

 

[serotonin2A]

All indoleamine hallucinogems tested so far (psilocin, DMT, DPT, and LSD) inhibit serotonin release, so that mechanism could contribute to the effects of that class of compounds but could not be the sole cause of any effects that are unique to 5-MeO-DMT. Also, the discriminative stmulus effects are not mediated by the same 5-HT1A population responsible for inhibiting serotonergic neurons.

 

[neurotic]

I think serotonin release from MDMA isn't altered by 5HT1A autoreceptor activation.

A reasonable dose of MDMA would stop any negative psychological effects from any psychedelic too, because it lifts your mood.

Does 5-MeO-DMT really inherently cause negative effects? I think it's reasonable to think that your heart will start racing after you vaporize a powerful hallucinogen and peak within minutes.

 

[zikzak]

WSH, have you experimented further with this?

 

[immad]

According to "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain" from 2014, 5-MeO-DMT is a 5-HT reuptake inhibitor with a potency between between Methylone and 4-FA and as such, might increase the serotonergic effects of MDMA if it is taken after the MDMA has been able to release a decent amount of serotonin.

 

[serotonin2A]

According to "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain" from 2014, 5-MeO-DMT is a 5-HT reuptake inhibitor with a potency between between Methylone and 4-FA and as such, might increase the serotonergic effects of MDMA if it is taken after the MDMA has been able to release a decent amount of serotonin.

Taking a 5-HT uptake inhibitor with MDMA would block the effects of MDMA; MDMA cannot release 5-HT if it does not enter terminals through SERT.

Nevertheless, 5-MeO-DMT may be a 5-HT uptake inhibitor in vitro, but the interaction with SERT isn't relevant to its in vivo effects in humans because it is 500-1000-fold selective for 5-HT1A versus SERT. The Ki values are approximately 3 nM and 3 uM, respectively.