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    Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use

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    • NoeticJuiceN
      NoeticJuice @Mauritio
      last edited by NoeticJuice

      @Mauritio said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

      If their flowers are the "real" one, their extract should be as well, right?

      Not necessarily. They already had the extracts before they started selling the flowers. If I wanted to be certain about getting the real plant, I would buy the whole flowers.

      @Mauritio said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

      I'm mainly interested in the anti-serotonin, pro-dopamine effect @Mulloch94 describes in the post I linked above. So whatever he had , I want.

      The mechanisms Mulloch94 wrote about are those of nuciferine and apomorphine, not necessarily those of the plant extract. But if you just want the same/similar subjective effects, then the product(s) you were thinking to buy could be fine.

      "We must remember that the only instrument of investigation we possess is our mind . . . The quality and condition of the telescope govern the observation resulting from its use. If there is dust on our lens, we see dark spots in the heavens."

      🎧🎶24/7

      MauritioM 1 Reply Last reply Reply Quote 0
      • NoeticJuiceN
        NoeticJuice
        last edited by NoeticJuice

        Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes

        Abstract
        Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor–receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist 3H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in 3H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists.

        I feel like these two threads should be connected
        "The dopamine system of healthy, highly creative people is similar to that found in people with schizophrenia"

        "We must remember that the only instrument of investigation we possess is our mind . . . The quality and condition of the telescope govern the observation resulting from its use. If there is dust on our lens, we see dark spots in the heavens."

        🎧🎶24/7

        MauritioM 1 Reply Last reply Reply Quote 0
        • MauritioM
          Mauritio @NoeticJuice
          last edited by

          @NoeticJuice said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

          I feel like these two threads should be connected
          "The dopamine system of healthy, highly creative people is similar to that found in people with schizophrenia"

          Well, hypomania is what we want , I guess .

          Dare to think.

          My X:
          x.com/Metabolicmonstr

          1 Reply Last reply Reply Quote 0
          • MauritioM
            Mauritio @NoeticJuice
            last edited by

            @NoeticJuice said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

            The mechanisms Mulloch94 wrote about are those of nuciferine and apomorphine, not necessarily those of the plant extract. But if you just want the same/similar subjective effects, then the product(s) you were thinking to buy could be fine.

            But he did get those effects (anti-serotonin and pro-dopamine) from the plant extract, so there should be some nuciferine and apomorphine in there. Or at least something that works along similar lines.

            Dare to think.

            My X:
            x.com/Metabolicmonstr

            1 Reply Last reply Reply Quote 0
            • lobotomize-meL
              lobotomize-me @cs3000
              last edited by

              @cs3000 ketanserin

              1 Reply Last reply Reply Quote 0
              • lobotomize-meL
                lobotomize-me
                last edited by lobotomize-me

                @NoeticJuice said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

                Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes

                From what I understand from this thread, along with the ones NoeticJuice mentioned, we should favor keeping 5ht2a relatively higher (compared to other 5ht receptors), since it antagonizes other 5 ht receptors and also decreases agonist effects on the D2 receptor

                NoeticJuiceN 1 Reply Last reply Reply Quote 0
                • NoeticJuiceN
                  NoeticJuice @lobotomize-me
                  last edited by

                  @lobotomize-me said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

                  decreases agonist effects on the D2 receptor

                  Based on the article, it seems like some 5-HT2A agonists enhance D2-mediated effects, but that is specific to the D2 receptors that are in the same heteroreceptor complex with the activated 5-HT2A receptor.

                  @lobotomize-me said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

                  keeping 5ht2a relatively higher (compared to other 5ht receptors), since it antagonizes other 5 ht receptors

                  I didn't know about 5-HT2A's interaction with other serotonin receptors before this. I asked Grok about it an it gave links to these two articles.

                  Cross-talk between 5-Hydroxytryptamine Receptors in a Serotonergic Cell Line: INVOLVEMENT OF ARACHIDONIC ACID METABOLISM

                  5-HT2B and 5-HT2A receptors of 1C11*cells are coupled with a PLA2-mediated release of arachidonic acid. Moreover, activation of the 5-HT2B receptor inhibits the 5-HT1B/1D receptor function, via a cyclooxygenase dependent AA metabolite. This 5-HT2B-mediated inhibition of the 5-HT1B/1D function can be blocked by a concomitant 5-HT2A activation.

                  Activation of 5-HT2A/C Receptors Counteracts 5-HT1A Regulation of N-Methyl-D-aspartate Receptor Channels in Pyramidal Neurons of Prefrontal Cortex

                  Taken together, our study suggests that serotonin, via 5-HT1A and 5-HT2A/C receptor activation, regulates NMDAR functions in PFC neurons in a counteractive manner. 5-HT2A/C, by activating ERK via the β-arrestin-dependent pathway, opposes the 5-HT1A disruption of microtubule stability and NMDAR transport.

                  I think that, for generally healthy people, a little more 5-HT2A could be beneficial. However, it's probably a bad idea for people with psychosis. At least for people with schizophrenia, it seems like their 5-HT2A receptors function differently from the norm + the extreme reliance on the left-hemisphere mode of perceiving probably doesn't help.

                  @cs3000 said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

                  a supersensitive coupling of 5-HT2AR to Gαi1 as opposed to Gαq has been identified in the postmortem brain samples of schizophrenia patients.

                  "We must remember that the only instrument of investigation we possess is our mind . . . The quality and condition of the telescope govern the observation resulting from its use. If there is dust on our lens, we see dark spots in the heavens."

                  🎧🎶24/7

                  1 Reply Last reply Reply Quote 0
                  • NoeticJuiceN
                    NoeticJuice
                    last edited by NoeticJuice

                    A basic theory of psychosis and related phenomena:

                    • The left hemisphere is extremely perceptually dominant.
                    • The left hemisphere distorts what is given by the right hemisphere, leading to hallucinations, delusions and a breakdown of reality.
                    • In a system that is dysfunctional in this way, reducing signal filtering at the thalamus acts as increasing fuel for the delusions etc., while in a person whose hemispheres are better balanced, it would instead fuel creativity.

                    Even if this theory is true, it would still only be a general, bigger-picture view. There are probably refinements and a lot more detail that could be added. For example, the information in the OP of this thread could be integrated, and more about specific brain regions could be added.


                    Some additional notes:

                    • In schizophrenia, it might not just be about left-hemisphere dominance but also right-hemisphere damage/deficit.
                    • IIRC, schizophrenics generally have reduced myelination in the brain. If their right hemispheres have less white matter than normal, then their right hemispheres, in a way, might be less right-brained than the average right hemisphere. Increasing myelination might be something worth looking into.

                    "We must remember that the only instrument of investigation we possess is our mind . . . The quality and condition of the telescope govern the observation resulting from its use. If there is dust on our lens, we see dark spots in the heavens."

                    🎧🎶24/7

                    U 1 Reply Last reply Reply Quote 0
                    • U
                      user2 @NoeticJuice
                      last edited by user2

                      @NoeticJuice said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

                      A basic theory of psychosis and related phenomena:

                      • The left hemisphere is extremely perceptually dominant.
                      • The left hemisphere distorts what is given to it by the right hemisphere, leading to hallucinations, delusions and a breakdown of reality.
                      • In a system that is dysfunctional in this way, reducing signal filtering at the thalamus acts as increasing fuel for the delusions etc., while in a person whose hemispheres are better balanced, it would instead fuel creativity.

                      Even if this theory is true, it would still only be a general, bigger-picture view. There are probably refinements and a lot more detail that could be added. For example, the information in the OP of this thread could be integrated, and more about specific brain regions could be added.


                      Some additional notes:

                      • In schizophrenia, it might not just be about left-hemisphere dominance but also right-hemisphere damage/deficit.
                      • IIRC, schizophrenics generally have reduced myelination in the brain. If their right hemispheres have less white matter than normal, then their right hemispheres, in a way, might be less right-brained than the average right hemisphere. Increasing myelination might be something worth looking into.

                      Little or no salt and meat, plus more plants, fruits, and dairy products can contribute to a person being more prone to visions ,“hallucinations”, dreams,Sunlight and EMFs can also contribute. In my experience, visions, hallucinations, and dreams are either manifestations of the body's internal agency/agency attempt, which may include stored engrams/memories from the person's past experiences, engrams/memories from other living beings/sources, that have entered the person's body in the past and have been stored, or direct receptions of information/energy from external sources, whether foods, drugs, emf, the sun, the moon, other living beings, or supernatural beings, which can include past, present, and future informations. It is not necessarily optimal in the long term to be prone to these things, as it can be associated with reduced physical/mental resilience or even damage.

                      Yet , once a person is in that state, visions/hallucinations/dreams can have a positive effect and lead the person towards a better internal agency and a better energetic state. Visions/hallucinations/dreams can contain elements that indicate to the person what they need to return to an optimal energetic state

                      NoeticJuiceN 1 Reply Last reply Reply Quote 0
                      • NoeticJuiceN
                        NoeticJuice @user2
                        last edited by NoeticJuice

                        @user2 I was thinking more in the context of things like schizophrenia or drug-induced psychosis.

                        I think visions are facilitated by the right hemisphere. In the case of visions without psychosis, while the person still remains sane, there's less distortion, so they can be better used for one's own benefit. I think it's similar for dreams.

                        Whatever people see from taking drugs is almost certainly distorted to a greater or lesser degree.

                        "We must remember that the only instrument of investigation we possess is our mind . . . The quality and condition of the telescope govern the observation resulting from its use. If there is dust on our lens, we see dark spots in the heavens."

                        🎧🎶24/7

                        U 2 Replies Last reply Reply Quote 0
                        • U
                          user2 @NoeticJuice
                          last edited by

                          @NoeticJuice i include schizophrenia or drug-induced psychosis in my comment above

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                          • MauritioM
                            Mauritio
                            last edited by Mauritio

                            While looking into studies on blue lotus (Nymphaea caerulea), I found a very interesting study on a plant from the same genus called N. lotus.

                            It was on mice with hyperprolactemia that received different dosages of N. Lotus, while bromocriptine served as the positive control group.

                            Not only was it able to lower prolactin, but at the highest dose, it lowered prolactin more than bromocriptine.At that dose it even lowered prolactin below the control groups value, which didn't receive prolactinergic medication .
                            They gave rats an HED of 30mg of Bromo, which is a hefty dose.
                            1000020982.png

                            On top of that it also drastically increased mices progesterone. Again, outperforming bromocriptine and even the control group.
                            1000020980.png

                            It also lowered estradiol.

                            I haven't done enough research yet, but that study alone makes me really want to try N. lotus.
                            https://scialert.net/fulltext/?doi=ajb.2017.91.98

                            Dare to think.

                            My X:
                            x.com/Metabolicmonstr

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                            • MauritioM
                              Mauritio
                              last edited by Mauritio

                              Here's another study in male animals where it had a positive impact on male reproductive health. They didn't test hormones, but numbers of offspring drastically increased in the N. Lotus group and sperm health did as well.

                              https://ppj.phypha.ir/browse.php?a_code=A-10-935-1&slc_lang=fa&sid=1

                              Dare to think.

                              My X:
                              x.com/Metabolicmonstr

                              1 Reply Last reply Reply Quote 0
                              • U
                                user2 @NoeticJuice
                                last edited by user2

                                @NoeticJuice said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

                                @user2 I was thinking more in the context of things like schizophrenia or drug-induced psychosis.

                                I think visions are facilitated by the right hemisphere. In the case of visions without psychosis, while the person still remains sane, there's less distortion, so they can be better used for one's own benefit. I think it's similar for dreams.

                                Whatever people see from taking drugs is almost certainly distorted to a greater or lesser degree.

                                If someone feel what he is seeing on drugs is real, it is real, real/reality is a feeling. If by distortion you mean not as real, not as true, illusory, it aint necessary any of these, potentially either the drug change the state/structure of the person temporary therefore the person perceive a different reality during this time, or what the person is seeing on drugs is the body inner agency/attempt to inner agency, and the differents drugs elements do manifest/are perceive as differents visual phenomenons, and it is all real

                                NoeticJuiceN 1 Reply Last reply Reply Quote 0
                                • NoeticJuiceN
                                  NoeticJuice @user2
                                  last edited by NoeticJuice

                                  @user2 said in Psychosis and serotonins 5ht2a receptor , HDAC and chronic anti-psychotic use:

                                  real/reality is a feeling . . . and it is all real

                                  (we already went over this in a different thread, although my thoughts have changed to some extent)

                                  Experience is real. Whatever we experience is real. However, there's more to reality than an individual's experience, and I feel it's still correct to say that some experiences are more aligned with reality than others.

                                  With the greatest understanding and clarity of perception, reality is truly beautiful. (Not that I'm in that state currently)

                                  However, if a drug makes a person experience an elevated mood or beauty (it's good to make a distinction between those two), it doesn't necessarily mean that they perceive with the greatest degree of clarity, and it could still be--and, I think, usually is--very warped.

                                  In the context of drugs, and also to some extent human experience in general, the rational (if it's right to call it that) mind warps perception to fit within its framework as well as possible.

                                  The process of clearing perception includes clearing away misconceptions in the framework, as well as getting more direct experience of reality without interference. These two aren't really that separated.

                                  "We must remember that the only instrument of investigation we possess is our mind . . . The quality and condition of the telescope govern the observation resulting from its use. If there is dust on our lens, we see dark spots in the heavens."

                                  🎧🎶24/7

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