So I don't have any formal education on pharmacology, but I am fascinated by how drugs work in general. I understand DMT is considered a hallucinogen of the psychedelic class and not a dissociative. But then how does one explain the "breakthrough" or "out of body experience" in high doses. What is the mechanism of action responsible for this? I see dissociative's work by being antagonists to the NMDA receptor, but I haven't found any information of DMT's ability to effect the NMDA receptor at all, antagonist or agonist. I would like to know the binding affinity of DMT at whatever receptor is responsible for the dissociative effects at high doses. Anyone have any links to this information or can give me any insight? I've tried searching forums and google and published documents. I may have read it and just not understood what it meant. Does anyone know?! Thanks!
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What is DMT's mechanism of action that causes dissociation?
- Thread starter Visionary
- Start date
Effects of psilocybin explained by a pHD
DMT is chemically so similar to psilocybin it is assumed they produce similar results.
Sounds like you know more than I about this so I only hope this talk contains some useful info for you.
Post what insights you find!
DMT is chemically so similar to psilocybin it is assumed they produce similar results.
Sounds like you know more than I about this so I only hope this talk contains some useful info for you.
Post what insights you find!
Sabnock1990
Be Your Own Shaman
There was some findings awhile back about how the reason Psychedelics work is because they activate the Serotonin 2A receptor within a Serotonin 2A to Metabotropic Glutamate 2 receptor complex, and that sole Serotonin 2A receptor activation doesn't cause Psychedelic effects, as evidenced by something like Lisuride, here's a quote from it's wiki page "While lisuride has a similar receptor binding profile to the more well-known and chemically similar ergoloid N,N-diethyl-lysergamide (LSD) and inhibits dorsal raphe serotonergic neurons in a similar fashion to LSD, a trait which indicates both drugs in the treatment of Parkinson's disease, it lacks the psychedelic effects of its sister compound. Newer findings suggest the lack of psychedelic action arises from the phenomenon of biased agonism. Stimulation of the 5-HT2A protomer within the 5-HT2A-mGlu2 receptor complex evokes psychedelic effects, while these effects do not occur during sole stimulation of monomeric 5-HT2A receptors. Accordingly, different G-proteins are involved. Lisuride behaves as an agonist at the 5-HT2AR monomer. Since it competitively antagonises the effects of LSD, it may be regarded as a protomer antagonist of the 5-HT2A-mGluR heteromer."
So it would seem that the connection with the Glutamatergic system would most likely be something with the Metabotropic Glutamate 2 receptor, quite possibly.
So it would seem that the connection with the Glutamatergic system would most likely be something with the Metabotropic Glutamate 2 receptor, quite possibly.
Thanks 5A8R3. I have seen videos from that PhD before and I enjoyed learning what I did from him, I will watch that video later, I probably will learn some more things, but I don't think it will help with what I am trying to understand, but I will give it a shot, thanks!
Thanks for your help ShamensStamen. I am not that knowledgeable to understand all that you wrote, but its not really what I'm trying to understand. I'm not trying to understand the visuals that are seen with closed eyes or open with psychedelics. I am wondering what causes the disconnection from the body with DMT. I understand Psilocybin and DMT are both in the tryptamine class of psychedelics and you would think they would be similar. But SWIM has never had an out of body experience with mushrooms, no matter how high of a dose. However on a pharmahausca experience SWIM had an hour long "breakthrough" and lost all feeling of their body, wasn't sure if their eyes were open or closed, or if they were alive or dead. SWIM didn't panic initially and didn't move to disrupt the trip and just let it take them where ever, but towards the end they wanted to come back and there were a few minutes of panic of not knowing if they ever would. So that leads me to wonder, what did that drug do to cause those effects. SWIM has never taken classic dissociative drugs (ie, ketamine, pcp, nitrous oxide, etc) So maybe SWIM is describing it incorrectly, but the feeling of being disconnected from the body was unlike SWIM has experienced before, and isn't that the "breakthrough" people talk about with DMT?
SWIM has vaped DMT many times but never achieved a breakthrough, the closest being some parts of their body losing sensation and not feeling there, but never the entire body. A glass genie was used and the product was of high quality, however tolerance and frequent use may have contributed to not being able to, and never using an MAOI while vaping. However many people report of being able to "breakthrough" on just DMT vaped. So this leads me to believe its not the MAOI that is responsible for the breakthrough. The MOAI is reported to contribute to the experience and obviously extends the experience, but its the DMT that causes the "out of body experience" since its achievable without an MAOI with some people and the correct circumstances.
Thanks for your help ShamensStamen. I am not that knowledgeable to understand all that you wrote, but its not really what I'm trying to understand. I'm not trying to understand the visuals that are seen with closed eyes or open with psychedelics. I am wondering what causes the disconnection from the body with DMT. I understand Psilocybin and DMT are both in the tryptamine class of psychedelics and you would think they would be similar. But SWIM has never had an out of body experience with mushrooms, no matter how high of a dose. However on a pharmahausca experience SWIM had an hour long "breakthrough" and lost all feeling of their body, wasn't sure if their eyes were open or closed, or if they were alive or dead. SWIM didn't panic initially and didn't move to disrupt the trip and just let it take them where ever, but towards the end they wanted to come back and there were a few minutes of panic of not knowing if they ever would. So that leads me to wonder, what did that drug do to cause those effects. SWIM has never taken classic dissociative drugs (ie, ketamine, pcp, nitrous oxide, etc) So maybe SWIM is describing it incorrectly, but the feeling of being disconnected from the body was unlike SWIM has experienced before, and isn't that the "breakthrough" people talk about with DMT?
SWIM has vaped DMT many times but never achieved a breakthrough, the closest being some parts of their body losing sensation and not feeling there, but never the entire body. A glass genie was used and the product was of high quality, however tolerance and frequent use may have contributed to not being able to, and never using an MAOI while vaping. However many people report of being able to "breakthrough" on just DMT vaped. So this leads me to believe its not the MAOI that is responsible for the breakthrough. The MOAI is reported to contribute to the experience and obviously extends the experience, but its the DMT that causes the "out of body experience" since its achievable without an MAOI with some people and the correct circumstances.
Sabnock1990
Be Your Own Shaman
"Thanks for your hemp ShamensStamen." lol, i had to laugh.
Also, i'm not referring to the visuals or anything, i'm talking about the effects of Psychedelics in general, there's definitely a Glutamatergic aspect there, and the Serotonin 2A to Metabotropic Glutamate 2 receptor complex could be the link you're looking for, as Psychedelics by activating the Serotonin 2A receptor within that complex, also interacts with the Metabotropic Glutamate 2 receptor which probably causes some Glutamatergic effects which could quite possibly lead to some similar effects as NMDA antagonists. I think a large part of the Psychedelic experience is Glutamatergic, which is why there are similarities, but also differences, compared to anti-Glutmatergics. It could be that the Psychedelics activate the Metabotropic Glutamate 2 receptor, or they antagonize, or otherwise modulate it, so that could potentially lead to some dissociative states.
As for not getting OBE's with Psilocin, how much have you taken so far of mushrooms? I've worked with DMT a lot, mostly orally with Harmalas/Rue or Moclobemide, but also a good bit of Harmala-heavy Changa, have had LSD a few times (up to 3 hits), had up to 2 hits of 25-D Nbome a couple times, and have had a handful of mushroom, as well as 4-ACO-DMT experiences with and without MAO-A inhibition using Harmalas/Rue or Moclobemide, and i've never had an OBE, though with the oral DMT i have had one moment where my body went completely numb, all i could feel was this sensation on my forehead, i saw a bright white light that was there with eyes closed and open, and it completely took me over/consumed me, then i threw up and slowly came back down. Have had plenty of death/dying experiences, but rarely ever see closed eyed visuals or visions, i've only had one vision on Pharmahuasca and that was a precognitive vision about my dad's death that came true 2 weeks later. So for me, most of what Psychedelics do are mental, physical, emotional and spiritual, rarely visual.
But yeah as far as being dissociated on DMT goes, never had that personally, no matter how much i've consumed (still haven't tried pure vaped DMT yet, but i will sometime or another), i've always felt sane, relatively sober but definitely altered lol, clear headed, aware, i've always felt in my body, my surroundings never disappeared or anything like that, and i've had some strong dosages of oral DMT (using Mimosa and Acacia root) and Changa.
Also, i'm not referring to the visuals or anything, i'm talking about the effects of Psychedelics in general, there's definitely a Glutamatergic aspect there, and the Serotonin 2A to Metabotropic Glutamate 2 receptor complex could be the link you're looking for, as Psychedelics by activating the Serotonin 2A receptor within that complex, also interacts with the Metabotropic Glutamate 2 receptor which probably causes some Glutamatergic effects which could quite possibly lead to some similar effects as NMDA antagonists. I think a large part of the Psychedelic experience is Glutamatergic, which is why there are similarities, but also differences, compared to anti-Glutmatergics. It could be that the Psychedelics activate the Metabotropic Glutamate 2 receptor, or they antagonize, or otherwise modulate it, so that could potentially lead to some dissociative states.
As for not getting OBE's with Psilocin, how much have you taken so far of mushrooms? I've worked with DMT a lot, mostly orally with Harmalas/Rue or Moclobemide, but also a good bit of Harmala-heavy Changa, have had LSD a few times (up to 3 hits), had up to 2 hits of 25-D Nbome a couple times, and have had a handful of mushroom, as well as 4-ACO-DMT experiences with and without MAO-A inhibition using Harmalas/Rue or Moclobemide, and i've never had an OBE, though with the oral DMT i have had one moment where my body went completely numb, all i could feel was this sensation on my forehead, i saw a bright white light that was there with eyes closed and open, and it completely took me over/consumed me, then i threw up and slowly came back down. Have had plenty of death/dying experiences, but rarely ever see closed eyed visuals or visions, i've only had one vision on Pharmahuasca and that was a precognitive vision about my dad's death that came true 2 weeks later. So for me, most of what Psychedelics do are mental, physical, emotional and spiritual, rarely visual.
But yeah as far as being dissociated on DMT goes, never had that personally, no matter how much i've consumed (still haven't tried pure vaped DMT yet, but i will sometime or another), i've always felt sane, relatively sober but definitely altered lol, clear headed, aware, i've always felt in my body, my surroundings never disappeared or anything like that, and i've had some strong dosages of oral DMT (using Mimosa and Acacia root) and Changa.
Hahaha hemp you.. lol I fixed that and other errors. Thank you for that insight!! I will look into that and try to learn and absorb what I can! I also am eager to ask a pharmacist acquaintance of mine, but I don't know how help she will be since she has no formal education on schedule 1 drugs or any personal experience with them.
SWIM has only been exploring psychedelic drugs for the past 6 months. SWIM has done as much as 11 grams of freshly dried of the cubensis genus. Note that SWIM is 230lbs so dosage is relative. There are plans for consuming the panaeolus genus eventually. DMT extracted and pharmahausca is the only other psychedelic variety SWIM has tried. Soon will be mescaline (peyote powder) and LSD-25 if SWIM can find a reliable source.
That is crazy you have never have closed eye visuals!! The visuals on dmt are so much more intense than on mushrooms. Sounds like you have just had dreamlike visions. After repeated use the DMT visuals from vaping became less and less. SWIM thought he may have damaged his brain or something... Until the pharmahausca blew SWIM away! SWIM was prepared and knew what to expect, but no matter what you can read, the experience for SWIM was very intense, and there is caution now in doing it again, or at least at that dose. SWIM may have experienced very mild (1-2%) psychosis if thats what it was, or just questioning and trying to integrate the experience. Trying to grapple with what is really real and what is not. However a week later SWIM appears to have returned to normal. SWIM essentially saw resemblances of death in the beginning, then the most beautiful awe inspiring place, the experience was ineffable. Its like SWIM saw what death was maybe even purgatory, and then went through that to the most beautiful blissful place for the remaining 50 mins which seemed much longer of course. SWIM isn't religious at all, but it has questioned their beliefs if there is really a soul or an afterlife. Its only been two weeks, but swim thinks about it a few times every hour, it changed them. Note SWIMS setting was good, but set was bad, SWIM understood the risks and wanted to face their demons, and SWIM is very thankful for the experience, it is what they truly needed.
SWIM has only been exploring psychedelic drugs for the past 6 months. SWIM has done as much as 11 grams of freshly dried of the cubensis genus. Note that SWIM is 230lbs so dosage is relative. There are plans for consuming the panaeolus genus eventually. DMT extracted and pharmahausca is the only other psychedelic variety SWIM has tried. Soon will be mescaline (peyote powder) and LSD-25 if SWIM can find a reliable source.
That is crazy you have never have closed eye visuals!! The visuals on dmt are so much more intense than on mushrooms. Sounds like you have just had dreamlike visions. After repeated use the DMT visuals from vaping became less and less. SWIM thought he may have damaged his brain or something... Until the pharmahausca blew SWIM away! SWIM was prepared and knew what to expect, but no matter what you can read, the experience for SWIM was very intense, and there is caution now in doing it again, or at least at that dose. SWIM may have experienced very mild (1-2%) psychosis if thats what it was, or just questioning and trying to integrate the experience. Trying to grapple with what is really real and what is not. However a week later SWIM appears to have returned to normal. SWIM essentially saw resemblances of death in the beginning, then the most beautiful awe inspiring place, the experience was ineffable. Its like SWIM saw what death was maybe even purgatory, and then went through that to the most beautiful blissful place for the remaining 50 mins which seemed much longer of course. SWIM isn't religious at all, but it has questioned their beliefs if there is really a soul or an afterlife. Its only been two weeks, but swim thinks about it a few times every hour, it changed them. Note SWIMS setting was good, but set was bad, SWIM understood the risks and wanted to face their demons, and SWIM is very thankful for the experience, it is what they truly needed.
Fidelsbeard
The Life You Ordered has Arrived
Not meaning to be rude but it isn't necessary to use "SWIM" as it can be distracting... it's ok to say "I" 
This paper overviews the binding affinities of DMT and a variety of other psychedelics.
Ray TS (2010) Psychedelics and the Human Receptorome. PLOS ONE 5(2): e9019. Psychedelics and the Human Receptorome
There appears to be a fairly interesting correlation between the substances that most effectively precipitate ego-loss experiences and agonism of 5ht1 receptor subtypes (in combination with 5ht2, a standard 5ht1 agonist has no psychedelic effect). I'm not sure the correlation is significant, but it could be an area worthy of further exploration.
Ray TS (2010) Psychedelics and the Human Receptorome. PLOS ONE 5(2): e9019. Psychedelics and the Human Receptorome
There appears to be a fairly interesting correlation between the substances that most effectively precipitate ego-loss experiences and agonism of 5ht1 receptor subtypes (in combination with 5ht2, a standard 5ht1 agonist has no psychedelic effect). I'm not sure the correlation is significant, but it could be an area worthy of further exploration.
I think it's sensory overload. If you receive more information from the senses than your counsciousness can handle, you can no longer put all of these little sensory puzzlepieces together.
And because you, and your body are part of the puzzle, they disappear in the mist, along with everything else.
And because you, and your body are part of the puzzle, they disappear in the mist, along with everything else.