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    Thread: Is the psychedelic ego death actually caused by adrenergic activity, not serotonergic activity?

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      Is the psychedelic ego death actually caused by adrenergic activity, not serotonergic activity?

      I think this belongs here.... I don't normally post in ED, so excuse me if it doesn't. This is just a theory right now, not based on a bunch of studies or anything (at least not that I know of), this is just the kind of stuff I think about in my free time and I thought this might add up.

      To my knowledge, it's been up to this point assumed that the ego death comes along with the other core effects of psychedelic hallucinations, generally thought to be caused by activation of serotonin receptors, particularly 5-HT2A. I'm no longer certain I believe this. My current theory is the effects related to ego death are actually caused by adrenergic receptors. Lately I've been reading up on the effects of adrenaline (epinephrine) and norepinephrine on the body and mind, and I've been surprised at what I found.

      Powerful adrenaline rushes (like really powerful) have been known to exhibit a wide range of effects, including strong time dilation, feelings of being in a dream or separate from normal reality, tunnel vision (i.e., loss of peripheral vision), loss of rational thought, loss of ability to comprehend colors, etc..... Basically, the more adrenergic activity you have, the more your brain starts shutting off different functions to put as much energy as it possibly can into increasing your focus on the moment. Now, how far this effect can go from adrenaline rushes alone is limited, because your body will either shut itself off when it realizes what's going on or you're going to have a heart attack, or a stroke, or something else terrible. All of that adrenaline isn't only causing central nervous system effects, but peripheral ones as well. BUT, some drugs can activate adrenergic receptors, or cause adrenergic activity to increase, with varying levels of activity relevant to the CNS and PNS. So with certain chemicals it's entirely possible to experience CNS adrenergic effects more intense than any normal adrenaline rush would get you without presenting the same physical danger.

      Now, what's interesting about this is that I had before had reason to think that increased adrenergic activity (especially norepinephrine) lowered NMDA receptor activity, which is the mechanism used by dissociative hallucinogens. If you know anything about dissociatives (which you probably do if you know anything about psychedelics), you'll know that the list of CNS effects I've given also matches up pretty well. I'd say one of the biggest differences is that the adrenergic effects cause you to focus intently, and pure dissociative effects cause you to unfocus. This would most likely be, in my opinion, because the adrenergic effects are shutting down everything BUT the part of your mind made to focus, and the pure dissociatives aren't keeping even that up. Another thing would be that when the effects are brought around by the adrenaline and norepinephrine, there's a much higher chance that you're going to be afraid than when going straight through the dissociative mechanism.

      Now, what does this have to do with anything? Well, if you know very much about the psychedelic ego death, you've probably already picked up on that. Fear, focus on the moment, time dilation, separation from reality, loss of ability to think rationally or comprehend the world.... These effects are crucial to the ego death experience! And most psychedelics (at least, most of the well-known ones) are extremely safe as far as effects on the PNS go, you can take absurd doses of them without becoming physically in danger. Nearly all psychedelics (and certainly all of them associated with ego death) have some adrenergic activity as well. So could it be that the ego death is actually a result of pushing these adrenaline-related effects beyond the limit of what is normally possible, all the way up to a total shutdown of all normal brain processing other than focus?

      So let's get to some drug examples. First, with psychedelics. I always found it bizarre that psychedelics could induce ego death at such varying levels of serotonergic hallucinations if these effects are supposedly activated through the same mechanism. Let's for instance take LSD and DMT. Anyone with experience with both of these chemicals will tell you that you can achieve ego death from LSD at a level of hallucination that looks like a joke compared to DMT. However, DMT "breakthroughs", a full out-of-body sensory overload experience brought on by serotonergic hallucinations, can be totally without ego death, something which is almost unimaginable with LSD, where a dose required to make you trip that hard would blow a hole through the fabric of reality. DMT is extremely similar to the tryptamines in your body (and is in fact one of them) like serotonin, and as a result very likely has far more serotonergic than adrenergic activity. LSD on the other hand is known to have a pretty good amount of adrenergic and even dopaminergic activity. So doesn't that seem to correlate? This can also be said of mescaline.

      And on that note, a perhaps even more sturdy example would be the difference between 5-MeO-DMT and bufotenine, two other endogenous psychedelic tryptamines. 5-methoxy tryptamines are often found to share similarities with psychedelic phenethylamines like mescaline and the 2Cs, and like them 5-MeO-DMT has been found to have some activity in inhibiting the reuptake of monoamines, including norepinephrine. 5-MeO-DMT is also known to cause an unbelievably strong level of ego death when smoked, despite having very little (if any?) 5-HT2A activity. Bufotenine on the other hand, which is the most similar psychedelic in structure to serotonin (with bufotenine being 5-hydroxy-N,N-dimethyltryptamine and serotonin being 5-hydroxytryptamine), likely has a higher serotonergic to adrenergic activity ratio than any other psychedelic, and it's known to create POWERFUL serotonergic hallucinations, with reports stating them to be much stronger than those created by DMT, and yet with little to no removal from reality or ego death-like effects whatsoever.

      On the subject of reuptake inhibitors, let's look at two important factors: serotonin reuptake inhibitors (SRIs) and norepinephrine reuptake inhibitors (NRIs), preferably selective. If the ego death is a result of high serotonergic activity, why don't any SRIs exhibit effects related to ego death? Overdose of them usually involves some mild sensory hallucinations, at best. Even kanna, which contains mesembrine (a supposed natural SRI that seems to be much safer physically than medical SRIs), when taken in large doses creates the normal psychedelic sensory hallucinations, but not ego death-like effects. However, atomoxetine, a NRI currently being used to treat ADHD, among other things, CAN create powerful dissociative experiences in overdose. I think that alone goes a long way in saying something here. Lastly, I'd like to mention dextromethorphan (DXM). There's a lot of debate in the drug community over whether dissociatives can cause ego deaths like psychedelics can (and of course with my theory here they absolutely can), but even among dissociatives DXM is often touted to be especially psychedelic-like. To my knowledge, DXM is also the only widely-used dissociative hallucinogen to have not insignificant effects on norepinephrine reuptake. Hmmm....

      However, where I think this is most interesting, personally, is its relation to naturally accessing the body's dissociative mechanisms. By which I refer to things like sleep paralysis and OBEs. I remember reading before of some monks (maybe monks? it's been a while since I looked it up) who practiced meditation and things like yoga nidra and other yogas to move beyond the dream state into a state of clear white light. Just like that experienced at the peak of ego death. Is it possible that, with this theory in mind, ego death is simply a step further than OBE in this mechanism and the point of that meditation is to reach it by being able to focus yourself so much that you can continue to push past the OBE and dream states? Of course, that part's mainly me thinking out loud for now....

      So that's where I'm at right now. Any thoughts? I know I didn't list any sources or anything, a lot of this is just using knowledge I've built up over a long, long period of research, so feel free to ask me about anything if you want to.

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      Heh, I know nothing on the subject, but I enjoy reading people's theories and their support behind it.
      ^___^
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      Very cool theory. I wish I could add more than that, but I don't know much about drugs in general and very little about ego death in particular. But very interesting
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      I believe all the answers you're looking for can be found in a book I'm currently reading called "Zen and the Brain" by James H. Austin, M.D. Unfortunately I'm only 70 pages into this 700 page book, so I can't answer much just yet, but I know a lot of the things you mention have been touched on and will be elaborated in later chapters. I highly recommend it. If you read through the reviews you'll understand what makes it so particularly great. Amazon.com: Zen and the Brain: Toward an Understanding of Meditation and Consciousness (9780262511094): James H. Austin: Books Maybe if you don't read it, then I'll revisit this thread when I'm finished with it and offer a better response.

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      ~Fantasizer~ <s><span class='glow_FF1493'>Alyzarin</span></s>'s Avatar
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      Thanks for the recommendation, I'll have to look into it!

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      I can't stop thinking about this now, if it's true there are a lot of things to reconsider.... :T

      What about stimulant overdose psychosis? No one's saying drugs like methamphetamine are safe, but you can definitely freak out and think that you're dying on a high dose of meth even when you're not actually physically in danger. Obviously part of the psychosis is from the dopamine release, but are the thoughts of death from the norepinephrine release (which I believe is actually a stronger effect of the drug than dopamine release)? Lots of people do report that there first two or three times using meth, or whenever they use it if they're one of those rare people who almost never use it (hah), have sort of a psychedelic or shamanic feel to it. That would definitely correlate with this, it would be just like taking a sub-ego death dose of a psychedelic but without the sensory stuff. Hmm....

      What about near-death out-of-body experiences, the kind so famously shown for example as hovering over your body after a car crash, and often involving speaking to dead relatives and the like? I wonder because I remember reading reports where people were hit by cars but not to the point of having one of those, and they had so much adrenaline pumping through them that they did feel like everything was a dream and they reached that level of color-blindness and the like. So what if their body was actually damaged badly enough to reach that NDE.... Is it because they had enough adrenaline pumping through them to reach a fully dissociative level of OBE? Of course having that amount of adrenaline should stop your heart, but guess what - it does. Because it's not a NDE if you don't nearly die, that's why those people having those hovering-over-their-body NDEs are shown being revived. So I wonder... are NDEs to psychedelics as regular OBEs are to dissociatives?

      So much to think about.... *rant*

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      Define ego death

      Everything works out in the end, sometimes even badly.


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      Well, I think I've gone over enough of the sensory aspects. Basically I'm referring to the feeling of your individuality fading away and not being separate from anything else in the existence, like you're just one with the energy and nothing but vibrations like everything else. At least, that's been my experience with it. And I'm not going to get into what it means or the reality behind it, that's up to personal beliefs.

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      So you're willing to speculate which chemical causes it but not speculate what is actually happening?

      Is there a difference?
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      Everything works out in the end, sometimes even badly.


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      I speculate all the time, I'm just not going into it in this thread. That's not what the thread is about. And yes there is, because speculating on what is actually happening requires speculating on what purpose, physical, spiritual, or otherwise, those chemicals have, rather than just what subjective effects they create.

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      Rational Spiritualist DrunkenArse's Avatar
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      Quote Originally Posted by Alyzarin View Post
      speculating on what is actually happening requires speculating on what purpose, physical, spiritual, or otherwise, those chemicals have, rather than just what subjective effects they create.
      How does speculating on what is "actually" happening require speculating on its purpose?
      Previously PhilosopherStoned

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      ~Fantasizer~ <s><span class='glow_FF1493'>Alyzarin</span></s>'s Avatar
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      Quote Originally Posted by PhilosopherStoned View Post
      How does speculating on what is "actually" happening require speculating on its purpose?
      Well, I guess it depends on how you're defining that, but when I think about what's actually happening I think about the objective reality and how it fits into the full picture, and whether it's just related to the brain as a physical thing, or a spiritual plane, or whatever. At the moment I'm only really interested in the subjective experience and which chemicals are causing it to happen.

      Maybe I'll put it this way. If I was trying to figure out what is actually happening, I would want to know what that chemical is doing to cause it. But that's not what I'm looking for with this, all I want to know is which chemical is doing it, no matter what that chemical is doing, so I can know in which situations it applies.

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      i think this could be correct when ever i do dmt a powerful psychedelic 15 seconds after inhalation i get a massive rush i feel my body on fire and intense panic and fear also like im about to die but it subsides pretty fast
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      I didn't read all that, but I think I disagree. There is no one singular mental/bio-chemical head space that is associated with ego death, there are many.

      Quote Originally Posted by Alyzarin View Post
      Well, I think I've gone over enough of the sensory aspects. Basically I'm referring to the feeling of your individuality fading away and not being separate from anything else in the existence, like you're just one with the energy and nothing but vibrations like everything else. At least, that's been my experience with it. And I'm not going to get into what it means or the reality behind it, that's up to personal beliefs.
      If that's what your defining it as then I disagree with it being caused by adrenaline. Am I the only one here's whos had ego death happen when I'm sitting still just looking at things? I've also experienced it while doing things but it's usually nothing involving any kind of adrenaline rush. But at the same time I'm not gonna say that an adrenaline rush can't be a catalyst for ego death; I don't think there;s one specific cause or any one garden variety experience if that's how you define it. Ego death happens all the time.

      I should mention that when I say sitting there I'm talking about when I'm not on drugs, though this also can happen when I am on drugs.

      Quote Originally Posted by Alyzarin View Post
      Fear, focus on the moment, time dilation, separation from reality, loss of ability to think rationally or comprehend the world.... These effects are crucial to the ego death experience!
      These aren't crucial to the ego death experience, they are just things that can be a catalyst. The same goes for psychedelics. Focus on the moment may be an exception, but I'm not sure, it depends on how exactly you define ego death. Being in the moment is always a part of it in some sense, but I'm not sure about focus. Usually it is.

      Reading the thing about the monks reminds me of something I've been experiencing that I wonder if others have as well. When doing some kind of breath work I sometimes start to feel a very very strong pleasure in my body. You could describe it as energy but that sounds more confusing than enlightening to me. It will get so strong that I'll have to stop. I dunno where I'm going with this, I should shut up and go to bed.
      Last edited by StonedApe; 04-03-2012 at 08:41 AM.
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      Lurker here, decided to register because I was interested in this thread.

      It's an interesting hypothesis, but I think I have to disagree. Ego death as an effect from psychedelics could still be explained by 5-HT receptors. You mention how 5-MeO-DMT produces very little visuals; this is in fact likely because it has very low affinity for 5-HT2a receptors (0.98). However, Serotonergic psychedelics effect a wide range of 5-HT receptors, not just 5-HT2a (which is believed to be the cause of primarily visual effects). Indeed, LSD actually has no affinity for Alpha-2B and Alpha-2C receptors.

      Because of this, it's more likely that Ego Death is facilitated by a 5-HT receptor other than 5-Ht2a. A good candidate might be the 5-HT7 receptors. These receptors are strongly affected by psychedelics commonly associated with Ego Death, like 5-MeO-DMT (3.69), N,N-DMT (4.00), and LSD (3.77).

      Just my two cents on the subject

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      Quote Originally Posted by Alyzarin View Post
      I think this belongs here.... I don't normally post in ED, so excuse me if it doesn't. This is just a theory right now, not based on a bunch of studies or anything (at least not that I know of), this is just the kind of stuff I think about in my free time and I thought this might add up.

      To my knowledge, it's been up to this point assumed that the ego death comes along with the other core effects of psychedelic hallucinations, generally thought to be caused by activation of serotonin receptors, particularly 5-HT2A. I'm no longer certain I believe this. My current theory is the effects related to ego death are actually caused by adrenergic receptors. Lately I've been reading up on the effects of adrenaline (epinephrine) and norepinephrine on the body and mind, and I've been surprised at what I found.

      Powerful adrenaline rushes (like really powerful) have been known to exhibit a wide range of effects, including strong time dilation, feelings of being in a dream or separate from normal reality, tunnel vision (i.e., loss of peripheral vision), loss of rational thought, loss of ability to comprehend colors, etc..... Basically, the more adrenergic activity you have, the more your brain starts shutting off different functions to put as much energy as it possibly can into increasing your focus on the moment. Now, how far this effect can go from adrenaline rushes alone is limited, because your body will either shut itself off when it realizes what's going on or you're going to have a heart attack, or a stroke, or something else terrible. All of that adrenaline isn't only causing central nervous system effects, but peripheral ones as well. BUT, some drugs can activate adrenergic receptors, or cause adrenergic activity to increase, with varying levels of activity relevant to the CNS and PNS. So with certain chemicals it's entirely possible to experience CNS adrenergic effects more intense than any normal adrenaline rush would get you without presenting the same physical danger.

      Now, what's interesting about this is that I had before had reason to think that increased adrenergic activity (especially norepinephrine) lowered NMDA receptor activity, which is the mechanism used by dissociative hallucinogens. If you know anything about dissociatives (which you probably do if you know anything about psychedelics), you'll know that the list of CNS effects I've given also matches up pretty well. I'd say one of the biggest differences is that the adrenergic effects cause you to focus intently, and pure dissociative effects cause you to unfocus. This would most likely be, in my opinion, because the adrenergic effects are shutting down everything BUT the part of your mind made to focus, and the pure dissociatives aren't keeping even that up. Another thing would be that when the effects are brought around by the adrenaline and norepinephrine, there's a much higher chance that you're going to be afraid than when going straight through the dissociative mechanism.

      Now, what does this have to do with anything? Well, if you know very much about the psychedelic ego death, you've probably already picked up on that. Fear, focus on the moment, time dilation, separation from reality, loss of ability to think rationally or comprehend the world.... These effects are crucial to the ego death experience! And most psychedelics (at least, most of the well-known ones) are extremely safe as far as effects on the PNS go, you can take absurd doses of them without becoming physically in danger. Nearly all psychedelics (and certainly all of them associated with ego death) have some adrenergic activity as well. So could it be that the ego death is actually a result of pushing these adrenaline-related effects beyond the limit of what is normally possible, all the way up to a total shutdown of all normal brain processing other than focus?

      So let's get to some drug examples. First, with psychedelics. I always found it bizarre that psychedelics could induce ego death at such varying levels of serotonergic hallucinations if these effects are supposedly activated through the same mechanism. Let's for instance take LSD and DMT. Anyone with experience with both of these chemicals will tell you that you can achieve ego death from LSD at a level of hallucination that looks like a joke compared to DMT. However, DMT "breakthroughs", a full out-of-body sensory overload experience brought on by serotonergic hallucinations, can be totally without ego death, something which is almost unimaginable with LSD, where a dose required to make you trip that hard would blow a hole through the fabric of reality. DMT is extremely similar to the tryptamines in your body (and is in fact one of them) like serotonin, and as a result very likely has far more serotonergic than adrenergic activity. LSD on the other hand is known to have a pretty good amount of adrenergic and even dopaminergic activity. So doesn't that seem to correlate? This can also be said of mescaline.

      And on that note, a perhaps even more sturdy example would be the difference between 5-MeO-DMT and bufotenine, two other endogenous psychedelic tryptamines. 5-methoxy tryptamines are often found to share similarities with psychedelic phenethylamines like mescaline and the 2Cs, and like them 5-MeO-DMT has been found to have some activity in inhibiting the reuptake of monoamines, including norepinephrine. 5-MeO-DMT is also known to cause an unbelievably strong level of ego death when smoked, despite having very little (if any?) 5-HT2A activity. Bufotenine on the other hand, which is the most similar psychedelic in structure to serotonin (with bufotenine being 5-hydroxy-N,N-dimethyltryptamine and serotonin being 5-hydroxytryptamine), likely has a higher serotonergic to adrenergic activity ratio than any other psychedelic, and it's known to create POWERFUL serotonergic hallucinations, with reports stating them to be much stronger than those created by DMT, and yet with little to no removal from reality or ego death-like effects whatsoever.

      On the subject of reuptake inhibitors, let's look at two important factors: serotonin reuptake inhibitors (SRIs) and norepinephrine reuptake inhibitors (NRIs), preferably selective. If the ego death is a result of high serotonergic activity, why don't any SRIs exhibit effects related to ego death? Overdose of them usually involves some mild sensory hallucinations, at best. Even kanna, which contains mesembrine (a supposed natural SRI that seems to be much safer physically than medical SRIs), when taken in large doses creates the normal psychedelic sensory hallucinations, but not ego death-like effects. However, atomoxetine, a NRI currently being used to treat ADHD, among other things, CAN create powerful dissociative experiences in overdose. I think that alone goes a long way in saying something here. Lastly, I'd like to mention dextromethorphan (DXM). There's a lot of debate in the drug community over whether dissociatives can cause ego deaths like psychedelics can (and of course with my theory here they absolutely can), but even among dissociatives DXM is often touted to be especially psychedelic-like. To my knowledge, DXM is also the only widely-used dissociative hallucinogen to have not insignificant effects on norepinephrine reuptake. Hmmm....

      However, where I think this is most interesting, personally, is its relation to naturally accessing the body's dissociative mechanisms. By which I refer to things like sleep paralysis and OBEs. I remember reading before of some monks (maybe monks? it's been a while since I looked it up) who practiced meditation and things like yoga nidra and other yogas to move beyond the dream state into a state of clear white light. Just like that experienced at the peak of ego death. Is it possible that, with this theory in mind, ego death is simply a step further than OBE in this mechanism and the point of that meditation is to reach it by being able to focus yourself so much that you can continue to push past the OBE and dream states? Of course, that part's mainly me thinking out loud for now....

      So that's where I'm at right now. Any thoughts? I know I didn't list any sources or anything, a lot of this is just using knowledge I've built up over a long, long period of research, so feel free to ask me about anything if you want to.
      This is all freakin GOLD. Your right on the money with most of what you said. What i want to know is, after experiencing ego death with LSD and also having the most intense OBE's through DMT.. why didn't i experience ego death with DMT? The whole time while experiencing ego death on LSD i was in an absolute awful place in my mind. I mean i sat on a couch in what should have been a very comfortable environment for a good 6 hours wondering "why aren't i dead yet", "why isn't the ambulance here yet", "why is everyone just walking by me like i don't exist". This trip changed me. Yet so did the most intense DMT trips I've experienced. The difference is, during a DMT trip its more like flying through space with no fear of whats going on.. and LSD taking me on a wild ride through the depths of what felt like hell. Keep in mind i put 3 hits of "sunshine" cid under my tongue while coming down from 2 grams of Mephedrone. Also this was my first ACTUAL trip from LSD after attempting it 2-3 times prior.

      What i want to know is what makes the DMT trip so much more tolerable even though it should feel more intense.

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