Thread: MAP-K Signaling Pathway Cancer?

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    MAP-K Signaling Pathway Cancer? 
    Hey guys, I hope every single one of you is doing amazing.

    Do you guys by chance know anything about MAP-K Signaling Pathways and their implication on cancer? I was watching Dr. David Nichols video on LSD Neuroscience and he mentioned how psychedelics go through various pathways when a ligand binds to a neurotransmitter. - - here is a screenshot of the process.

    One of these pathways is the MAP-K Pathway and I've noticed that constant overstimulation of this pathway can result in the growth and multiplication of cancerous cells.

    After talking to Dr. Nichols about my symptoms, he believes that there's a chance that my 5ht2a receptors could have been sensitized causing my HPPD-like symptoms where I have mild visuals in the absence of a hallunciogen. When I asked him how this receptor sensitization could happen if receptors are constantly recycled on a weekly basis, he said that it was a result of intracellular signaling cascades.

    If that's the case, would that mean that my MAP-K pathway has become sensitized and as a result, I've left myself much more susceptible to cancer until I get on an inverse agonist of the 5ht2a receptors - which shuts off any constituital activity at the receptor site.

    In addition to this, I found an anecdotal report of a 25i user who had an undiagnosed brain tumor. - - Screenshot of the post.

    Is this just a random coincidence? Am I going to develop cancer unless I get on a 5ht2a inverse agonist? Or is the MAP-K Pathway overstimulation and dysfunction a result of a genetic susceptibility or mutation?

    I'm honestly scared to death.. I don't want to develop cancer just because of a stupid mistake I made as a 17 year old..

    I have a psychiatrist appointment in a couple of days and I wonder if I should tell them about this and get an MRI done? Or even recommend the 5ht2a inverse agonist.
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    Bluelighter mr peabody's Avatar
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    Think I found that lecture here.

    Maybe write to Dr. Nichols here:

    [email protected]

    I'd like to copy your post and its responses to "Psychedelics and cancer", if you don't mind.

    I also I found this:

    Targeting the MAP K Signaling Pathway in Cancer

    Last edited by mr peabody; 16-04-2018 at 04:28.
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    Go for it my man, Does my rationale make sense? Do I have reason to be worried or am I being a hypochondriac. Would this mean that people with sensitized receptors likely from HPPD are more susceptible to cancer due to constant MAP-K pathway activity? It would make sense for 25i to sensitize receptors since it has such a high affinity at 5ht2a in addition to being a full agonist

    From what I know, this constant MAP-K activity pathway results in cells abnormally growing and multiplying and eventually becoming cancerous.
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    Bluelighter mr peabody's Avatar
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    Honestly, I don't know, but I'll bet Nichols does. I'm sure he could advise a next step for you, in any case.
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    Could you guys please send him an email at [email protected]?

    Specifically asking him about 5HT2A receptor sensitization and how this might leave someone more susceptible to cancer due to constant intracellular signaling cascades going off through the MAP-K pathway?

    This could save so many lives and prevent cancer in HPPD sufferers who might have this 5HT2A sensitization due to intracellular signaling cascades which cause the visuals that HPPD users see.

    Please, please if some of you could send him this email so that he could see it and it is really brought to his attention, id really appreciate it. I want to maximize harm reduction.. I can't imagine developing cancer as a result of a stupid mistake I made as a 17 year old.
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    Shadowmeister's Avatar
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    Man you came here a while back about consuming 25i and worrying about some other damage, right? Either way, heed this advice: please stop obsessing about this stuff. Anxiety/chronic stress is really bad for you, that's for 100% certain. You can't know what the future holds and worrying about it endlessly doesn't do you any good. You already took 25i, nothing you can do about it now. What you're experiencing right now has a name... it's called hypochondria, and it's a real problem for some people. It's good you're going to a psychiatrist, I think you should tell them that you're having a lot of difficulty not being anxious about and thinking about whether you damaged yourself. It sounds like you're having obsessive thoughts (especially if you were indeed one of the people who had a thread about 25i damage months ago) and that's not good, but it's also treatable, particularly through techniques like Cognitive Behavioral Therapy. Learning to understand when you're in a negative thought loop and breaking out of it instead of being a slave to it.

    I'm not even saying this topic isn't worth discussing, because it could be. It just sounds like you're coming at this from a place of fear/anxiety/obsession rather than a place of curiosity.

    I apologize if I'm misreading you here, it's just that we see a lot of people creating massive anxiety in their lives through worrying about a past trip.

    Good luck man!
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    Quote Originally Posted by jacktheripper42 View Post
    Could you guys please send him an email at [email protected]?

    Please, please if some of you could send him this email so that he could see it and it is really brought to his attention, id really appreciate it. I want to maximize harm reduction.. I can't imagine developing cancer as a result of a stupid mistake I made as a 17 year old.
    Okay let's not bug Nichols any more, Jack has already sent him tons and tons of messages and Nichols has already asked Jack to stop emailing him plenty of times. I've seen the email conversation screenshots that Jack has sent me, Nichols was at his wit's end long ago with Jack

    Jack has some serious anxiety/OCD type stuff (Nichols said the same thing) and we should be careful to avoid legitimizing any fears that Jack has. Nichols has advised Jack to seek serious professional help and Jack has seemingly failed to seek any help from mental health professionals.

    5-HT2A sensitivity does not explain the visual disturbances that HPPD sufferers experience. Nor do I believe that Jack's visuals are even outside the range of normal, especially when he has anxiety, really messed up breathing/hyperventilation/panic attacks and is sleep deprived. All of which can cause visual disturbances. He's super hyperfocused on his visuals. All humans have visual disturbances. Our vision is not perfect.

    I believe Nichols is a fabulous chemist but I don't believe that one should be turning to Nichols for mental health advice, as he seems to be unfamiliar with these sorts of anxiety cases. There have been a couple people I've communicated with who have had a similar deal as jack - took a substance, eventually developed anxiety (sometimes 9 months later) and then hyperfocused on the drug as the cause, even though they were fine for xyz amount of time after taking the drug.

    In Jack's case, he was better until Nichols mentioned possible 5-HT2A sensitization contributing to visuals. Then Jack went down the anxiety/obsession rabbit hole again. But jack has admitted he already got better with mindfulness meditation once.

    Considering 5-HT2A antagonists don't seem to help with HPPD cases in the literature, in fact there are reports of potent 5-HT2A inverse agonists such Risperidone worsening HPPD visuals, and from talks I've had with a PhD neuro with a keen interest in psychedelics, 5-HT2A sensitization does not explain HPPD visuals and anything to do with 5-HT2A is an unhelpful obsession for the OP.

    If 5-HT2A sensitization caused HPPD visuals, then HPPD would be super easy to treat. Unfortunately that is not the case. For the record, I still don't believe the OP actually has HPPD. One school of thought is that before diagnosing HPPD, its important to rule out other conditions that can feature visual disturbances, and that certainly hasn't been done in OP's case. Not to mention that I still don't think his visual disturbances are very consistent with HPPD, nor are they outside the range of normality in terms of severity.

    Okay I've said my $0.02, peace out all

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    Look y'all. Thank you so much for helping me out with all your input, especially you Cotcha. So the intracellular cascades occurring that produce hallucinations in the absence of a hallucinogen has nothing to do with 5HT2A intracellular signaling cascades? I mean map activation wouldn't cause visuals right?

    You can see how this could scare me if Nichols has speculated that my visuals are a result of 5HT2A sensitization due to intracellular cascades. I asked him how this could happen if the receptors are constantly recycled and he said that it's a result of signaling through various cascades. IF that is the case wouldn't it mean there's a possibility that my MAP-K pathway is constantly being stimulated leaving me susceptible to cancers until I halt the stimulation of this pathway. Like I said before, I'm trying to maximize harm reduction.

    If this pathway was sensitized, I'll get on the proper medication to stop it and potentially save my life and that of others who have HPPD as a result of intracellular cascades sensitization. I know I sound like a broken record now but this is actually really bothering me.

    Let's just say Nichols was accurate in his speculation. That my receptors are producing visuals due to intracellular cascades. What other route would the cascades go other than constant MAP-K activity causing visual symptoms? Are there other pathways through these cascades that could cause visuals?
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    Just let it go, man. Even if this is at the root of your issues, what are you going to do about it? Take an inverse agonist that as Cotcha said is likely to worsen your symptoms? If you want to reduce your risk of cancer, eat healthy, get enough exercise, and socialize often. Like Xorkoth said the stress you're putting your body through worrying about this is probably a greater contributor to your risk of cancer, or at least an ulcer

    Everything we know about this stuff is just barely beyond speculation, you're as likely to do more harm to yourself as to fix anything
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    Quote Originally Posted by jacktheripper42 View Post
    IF that is the case wouldn't it mean there's a possibility that my MAP-K pathway is constantly being stimulated leaving me susceptible to cancers until I halt the stimulation of this pathway.
    Arrestin mediated MAPK signaling is technically self-halting.

    I see this all the time - Joe Blow tries to interpret scientific literature and just ends up giving himself anxiety over a misinterpretation

    The scenarios where someone has excess stimulation of MAPK (via arrestin) and excessive 5-HT2A sensitivity are mutually exclusive. Arrestin activity will lead to receptor downregulation. That's really what arrestins primarily do, mediate receptor desensitization, endocytosis/regulation. So yes, under certain circumstances, excessive agonist binding at 5-HT2A can lead to MAPK activation after arrestin recruitment.

    But arrestin recruitment implies downregulation. So don't be worried about having both persistent arrestin mediated MAPK activation and 5-HT2A receptor hypersensitivity existing at the same time. In other words, this MAPK theory is incompatible with the 5-HT2A sensitivity theory. I don't know if you've noticed, but you've been straw-grasping for quite some time, latching onto any possible explanation. That's quite common with anxiety and hypochondriacs as well

    I can't believe how worried you are about cancer now, but it just goes to show that researching doesn't help. It only fuels the fire, it gives you more things to be anxious about
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    Damn that actually reassured me a lot. Thanks Cotcha :-). What do you honestly think causes HPPD then if its not 5ht2a supersensitization, maybe new brain pathways being developed that weren't there before? I see auras around objects and things do really get bigger and smaller if I focus on them. Like I'm looking at the edge of my wall right now, the corner of it. The corner itself has a big white column that is separated by a teal and pink covered wall. When I look at this wall I see the column bending slightly and the teal and pink color pattern also seems to be breathing somewhat. I then look at my T.V. and it has a slight aura around it. Same with any other object. When I wave my phone in front of my face in a dark room but I don't directly look at it and I look at the background - I see a visual trail for a bit. All of these things become worse when I'm stressed.

    What do you honestly think could have caused HPPD if it's not related to something with 5ht2a? I mean NBOMe is a high affinity full agonist at 5ht2a so don't you think there could be something wrong with this receptor causing a specific kind of HPPD. 25i doesnt really hit any other receptors with any sort of significance. Do you think my HPPD will go away on its own? Does it have anything to do with 5ht2a? I just don't get why so many people that do 25i get HPPD.
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    It seems like the outer edges of every object slightly vibrate/breathe? Is this normal? If not will it go away? I associate these symptoms with some malfunctioning of my 5ht2a receptors which causes my anxiety because I wonder what other functions are being altered OTHER than just my visual symptoms. As you know 5ht2a affects so many different functions in the body. Is this 5ht2a alteration why I'm experiencing panic attacks? Or is it just how I'm reacting to it...

    It probably is how I'm reacting to it because I felt better after stopping my obsessions BUT I've always felt slightly off.. Will my brain go back to baseline or will I have these visual distortions for the rest of my life?
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    Bluelighter Bagseed's Avatar
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    Bad trips can cause anxiety and hppd in individuals.

    Psychotherapy and maybe medication is your best bet. Obsessing over possible neurochemistry implications you cannot comprehend will make things worse for you, no doubt.

    Your drive to find a physical explanation to your mental health problems will only be counterproductive and take you deeper down that rabbit hole.

    Maybe in a few decades, when neuroscientists actually have a fundamental understanding of the brain, things will be different. But for now, this will only drive you crazy.
    Last edited by Bagseed; 17-04-2018 at 09:43.
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