MAOI's block DMT

[Nibs]

Came across a nearly 25 year old article that was written by MAPS that makes a very compelling case that MAOI's actually block the effects of serotonin antagonists (triptamines, phenylethylamines, ergolines). By increasing serotinin levels with an MAOI via intramuscular, intravenous, or inhalation, it severly degrades the effects of substances such as DMT and LSD. Interesting it might have benefits at low doses with mescaline, and nothing has been studied with Psilocin. "Since data on related visionary tryptamines DMT and LSD suggest conventional wisdom on this point is wrong, any potentiation of psilocybin by MAOI would be an anomaly, hardly expected - certainly not to be taken for granted." If this is true, which it appears it most likely is, then substances such as changa and its ability to potentiate DMT has been falsely subjective, and this also applies to dosing MAOI's while tripping on LSD.
*Note This does not apply to oral MAOI's in conjunction with oral triptamines.

Lately I have been exclusively predosing with Rue or Caapi before smoking DMT, and i can say that my visials have not been all that mind blowing, only when I smoke fairly large amounts do they become vivid, and this must be because i am forcing the DMT to overpower the MAOI. Ive been a big fan of changa, but after reading this ill be going back to taking DMT neat for a while and see how that goes.

Link to the full article:

MAPS - Pharmahuasca: On Phenethylamines and Potentiation

 

[monomind]

The aim of changa is not to potentiate the dmt but rather to create a synergy that will make the experience less crazy and more integrative. So I dont think potentiation is really the point with Changa.

When smoking caapi or rue while under the influence of psilocybin there are dramatic potentiation effects.

 

[OneIsEros]

As the last post mentioned - try smoking a few bowls of rue on either ayahuasca or mushrooms sometime. It is overwhelmingly powerful.

 

[bismillah]

Ok, well, I can say that the idea is just plain wrong—at least as far as my subjective experience is concerned.

To put it succinctly:

15mg of dmt: meh

15mg of dmt after rue tea: why is there a kaleidoscope stuck to my eyeballs

Mind you, I don't feel anything (not even a little bit) from 3g of rue until after I add DMT to the mix. When the two are combined it hits like a sack of bricks, even at a low dose.

Also, I don't pretend to be a neurochemist, but doesn't DMT *displace* serotonin in the brain? I'd think we wouldn't really be able to trip at all if it didn't.

 

[dragonrider]

This is something that has been discussed before, and the interesting thing is that different people have very different experiences with MAOI's and 5-ht-2 agonists.

Some people say it potentiates mushrooms and other psychedelic drugs, while others say it weakens them.

Personal metabolism may play a role, but also ROA, and time taken between administration of both substances.

Increased levels of serotonin should indeed diminish the effects of these 5-ht2a agonists, so i suppose that the longer you wait after administring a MAOI and a psychedelic, the more it could weaken the effects of it, by increasing levels of serotonin.

On the other hand many of these substances are also breaken down by the enzyme, so MAOI's may also increase the amount of these psychedelics that actually reach the receptors in the brain.

And then there is the fact that most of the MAOI's taken this way, also increase levels of dopamine and noradrenaline, wich both also have the potential to make the experience more intense or rewarding. An adrenaline rush, wich is actually a noradrenaline rush, often makes us experience things more intensely, and dopamine is often being called "pleasure molecule".

So it seems complicated. The levels of these substances, already in your blood when taking them, must also play a role.

 

[Sabnock1990]

Idk about other substances, but neither Rue/Harmalas nor Moclobemide lessen the effect of DMT or Psilocin, definitely potentiates them and makes them last longer, the increase in neurotransmitters i do think makes the headspace clearer/cleaner though, more soberish but the psyches definitely still work just fine. Idk about LSD or Mescaline or others though. SSRI's have a different mechanism for raising Serotonin and imo should definitely get in the way of psyches working, but MAO-A inhibition raises background Serotonin, not foreground Serotonin, imo/ime, so the background Serotonin is raised by substances which can raise Serotonin, as opposed to having foreground Serotonin forced into the synaptic cleft via SSRI's which would compete with psyches for Serotonin receptor agonism.

I always dose my Rue/Harmalas about an hour before dosing my DMT or Psilocin, or when using Changa i always smoke the Rue/Harmalas beforehand or with it.

 

[King Tryptamine]

Firstly it is important to note that not all psychedelics function as antagonists towards the 5-HT2A receptor with the exception of a few like 2-CB. Instead the majority of them function as partial agonists as is the case with psychotropics like LSD, 4-HO-DMT and mescaline. So they block out the endogenous ligand, in this case 5-HT whilst also partially stimulating the receptor itself. This interaction changes the structure of the protein and causes the dimerisation between the 5-HT2A and mGlu2 receptors producing a unique signaling cascade that leads to psychedelia.

Now when increasing serotonin levels via harmine, harmaline or even something with a different pharmacodynamic profile like MDMA I don't see how a full agonist such as 5-HT will block out the effects of said psychedelic. Instead I find the reverse scenario more likely to occur in which the administered psychedelic such as LSD to diminish the effects of serotonin at the 5-HT2A site functioning as a high affinity partial agonist.

IMO opinion it is clear that RIMA's such as harmine and harmaline significantly potentiate tryptamines like N,N-DMT. Not just through subjective experience but the pharmacological data is also out there on sites such as NCBI. The primary mechanism being MAO-A inhibition and therefore increased half life of N,N-DMT in regions such as the gut, brain and blood.

 

[dragonrider]

Firstly it is important to note that not all psychedelics function as antagonists towards the 5-HT2A receptor with the exception of a few like 2-CB. Instead the majority of them function as partial agonists as is the case with psychotropics like LSD, 4-HO-DMT and mescaline. So they block out the endogenous ligand, in this case 5-HT whilst also partially stimulating the receptor itself. This interaction changes the structure of the protein and causes the dimerisation between the 5-HT2A and mGlu2 receptors producing a unique signaling cascade that leads to psychedelia.

Now when increasing serotonin levels via harmine, harmaline or even something with a different pharmacodynamic profile like MDMA I don't see how a full agonist such as 5-HT will block out the effects of said psychedelic. Instead I find the reverse scenario more likely to occur in which the administered psychedelic such as LSD to diminish the effects of serotonin at the 5-HT2A site functioning as a high affinity partial agonist.

IMO opinion it is clear that RIMA's such as harmine and harmaline significantly potentiate tryptamines like N,N-DMT. Not just through subjective experience but the pharmacological data is also out there on sites such as NCBI. The primary mechanism being MAO-A inhibition and therefore increased half life of N,N-DMT in regions such as the gut, brain and blood.

Yes, this is usually the case. However, i can remember having read in some previous threads, that there where some people who reported diminished effects after having taken an MAOI.

So for some reason it does seem to differ from person to person.

I don't know how to explain this phenomenon. There are so many factors at play.

 

[BecometheOther]

MAOIs potentiate mushrooms for sure, by alot.

 

[downwardsfromzero]

It's worth remembering that the MAOI's will interact with other parts of the metabolism (CYPxxx in the case of harmalas, for instance). This in turn will influence the metabolic outcomes in processing a number of other active molecules. What if individual variations in the cytochrome P450 system are responsible for differentiating the two seemingly contradictory experience sets for the interaction of MAOI with psychedelics?

 

[dragonrider]

It's worth remembering that the MAOI's will interact with other parts of the metabolism (CYPxxx in the case of harmalas, for instance). This in turn will influence the metabolic outcomes in processing a number of other active molecules. What if individual variations in the cytochrome P450 system are responsible for differentiating the two seemingly contradictory experience sets for the interaction of MAOI with psychedelics?

Yes, i think it is much more complicated than it may seem at first.

For me personally, harmala's do indeed amplify the effects of shrooms. But even within this group there seems to be a lot of variation between individuals, because i would say for me it is an amplification of maybe 10 to 20 %, but some people say that with harmala's they only need half the amount of shrooms they normally take, to get the same results.