Antipsychotics, strength and opinions.

[bigjackaal96]

The fact that they are so dirty is only accepted because they are generally reserved to those struggling with severe mental illness.

Gutter trash meds made when Psychosis receptor/neuron cause was almost none data wise with no room to propose HF psychosis without abuse. It literally took doctors testing out PCP to find out NMDA becomes inhibtory through damage/mutation. D2 receptors grow to compensate for the sudden CNS depression common with Ketamine at high doses. Other receptors/Neurons then rewire to avoid NMDA since they won't get any agonist effects leading to AMPA to upregulate as fall back. CNS ACH drops hard from M1 & a7 leaving the brain with no signal to noise centre which causes the unmasking episodes, Still view the bug visuals on DPH Is folk unware the house Is a house fly graveyard. Norepinephrine Is upregulated to mimic the fear/panic that high NMDA would produce, If too high you end up with Paranoid SZ.

The brain even roids out size/neuron/connection because It isn't bound by NMDA agonist toxicity getting in the way. Even ASD-2 & higher(Classic autism) Is from NMDA Inhibtory caused by Anti-NMDA immune attack in the womb & other reasons.

Dissos induce the same effects as classical psychosis with the psychadelic layer from D2 agonism and are seen as easiest of the 3 Hallucinogen types, Despite in theory being stronger than Deliriants by a factor of 2.

Deliriants/Delirium have much better meds with most of them able to abort a full trip instantly.

 

[paranoid android]

Ive had psychosis and can confirm that antipsychotics do work. Zyprexa seems to work the best with the least side effects.

In my experience neither dissociatives or psychedelics are anything like psychosis. It's dfar more like high doses of dimenhydrinate which i did once when i was young and didnt have internet in my defense.

 

[3DQSAR]

Gutter trash meds made when Psychosis receptor/neuron cause was almost none data wise with no room to propose HF psychosis without abuse. It literally took doctors testing out PCP to find out NMDA becomes inhibtory through damage/mutation.

it was my understanding that the cerebrospinal fluid samples were taken from around 300 people who suffered long-term psychotic illnesses and analysis revealed elevated levels of DOPAC (a dopamine metabolite) and/or reduced levels of NMDA.

A few years ago Eli-Lilly developed a new class of medications that were NMDA modulators. It turned out to work well and be well tolerated in some people but ineffective in others. But it's my suspicion that medical ethics has changed significantly enough for it to be impossible to take cerebrospinal fluid from someone who isn't able to give informed consent so it's not confirmed that the people it worked for were in the subgroup of ONLY having low levels of NMDA. After all, I doubt an ethics committee would allow patients to be given PCP in this day and age.

A real lost chance. As it only worked for a minority of patients, research was dropped. But for that group, it could have been a much better treatment option.

If DOPAC and NMDA levels were studied by Eli-Lilly and I just missed the paper, I would really appreciate someone providing the DOI. Thanks.

 

[bigjackaal96]

A few years ago Eli-Lilly developed a new class of medications that were NMDA modulators. It turned out to work well and be well tolerated in some people but ineffective in others. But it's my suspicion that medical ethics has changed significantly enough for it to be impossible to take cerebrospinal fluid from someone who isn't able to give informed consent so it's not confirmed that the people it worked for were in the subgroup of ONLY having low levels of NMDA. After all, I doubt an ethics committee would allow patients to be given PCP in this day and age.

They already have a NMDA antipsychotic that from a M1 & M4 Agonist + non-BBB ACH blocker to stop bowel/body side effects. They can check through MRI/Brain scans to see If NMDA comes off as dark areas while Dopamine lights up as white.

 

[Smyth2]

I found out about the Liming Shao guy I mentioned in a few of the other posts designed an antipsychotic that is almost clinically approved.

It is called Ulotaront.

[1] Dedic N, Jones PG, Hopkins SC, Lew R, Shao L, Campbell JE, Spear KL, Large TH, Campbell UC, Hanania T, Leahy E, Koblan KS. SEP-363856, a Novel Psychotropic Agent with a Unique, Non-D2 Receptor Mechanism of Action. J Pharmacol Exp Ther. 2019 Oct;371(1):1-14. doi: 10.1124/jpet.119.260281. Epub 2019 Aug 1. PMID: 31371483.
[2] Liming Shao, et al. WO2011069063 (Sunovion Pharmaceuticals Inc, PGI Drug Discovery LLC).

You have to be careful with antipsychotics to pick one without the extrapyramidal effects. For example, I was only able to last one injection on zuclopentixol and a couple of months on haloperidol before switching.

The best one is quetiapine (300mg/d), olanzapine does work but the dosage was always too low at 20mg per day. I could probably tolerate 100mg per day of olazapine if the dose went that high. I bought one on line called chlorpromazine that works quite well but I haven't bothered to buy more of it lately (it is non-addictive). I'm currently receiving a once every three months depot of paliperidone but I cannot feel any effects from it either good or bad.

 

[3DQSAR]

https://www.empr.com/home/news/drugs-in-the-pipeline/disappointing-results-for-ulotaront-in-two-phase-3-schizophrenia-trials/

Ulotaront appeared to fail in human trials. I think I've mentioned this before but the MAJORITY of medicines that reach human trials still fail to receive a GSL.

That they are attempting to repurpose if for generalized anxiety disorder

It's very hard to model psychosis and it does appear that if one uses a drug to produce the symptom (dizocilpine was used - I don't know it that has changed), it apparently doesn't fully model the illness.

It's one of those areas of medicine in which dirty (promiscuous) ligands are the ones that most often succeed. It may well be the case that no two people actually share exactly the same disruption of brain chemistry so a medicine that WILL treat them all has to target every receptor associated with the disease.

To me, this seems like the best case for personalized medicine i.e. it may take an increased number of medicines to allow only those targets needed for treatment ARE modulated.

My wife used to be a support worker for people struggling with psychotic disorders and it's interesting to note that her simple logic is that a patient should have the right to choose which (if any) medication they consume.

There was a local character called 'Purple Ronnie' who had what I presume to be paranoid schizophrenia. He was convinced there were snipers on the rooftops and that the only 'pure' water came from the well in his garden. But he was a bit odd but not a risk to anyone. In his words 'I don't take medication because when I do, I don't feel like me'.

It frustrates me that people are presumed to have NO judgement if diagnosed with a psychotic disorder. A black and white divide between compos mentis and non-compos mentis. Even I am aware that such disorders can vary from day to day. Another friend does get a medication prescribed but they decide when they NEED it. That friend saw how ill I was and was the only person who checked on me every day for weeks. He stayed over a few times and I guess I ow him my life, but for many years he was forced to take medication.

 

[bigjackaal96]

https://www.empr.com/home/news/drugs-in-the-pipeline/disappointing-results-for-ulotaront-in-two-phase-3-schizophrenia-trials/

Ulotaront appeared to fail in human trials. I think I've mentioned this before but the MAJORITY of medicines that reach human trials still fail to receive a GSL.

That they are attempting to repurpose if for generalized anxiety disorder

It's very hard to model psychosis and it does appear that if one uses a drug to produce the symptom (dizocilpine was used - I don't know it that has changed), it apparently doesn't fully model the illness.

It's one of those areas of medicine in which dirty (promiscuous) ligands are the ones that most often succeed. It may well be the case that no two people actually share exactly the same disruption of brain chemistry so a medicine that WILL treat them all has to target every receptor associated with the disease.

To me, this seems like the best case for personalized medicine i.e. it may take an increased number of medicines to allow only those targets needed for treatment ARE modulated.

My wife used to be a support worker for people struggling with psychotic disorders and it's interesting to note that her simple logic is that a patient should have the right to choose which (if any) medication they consume.

There was a local character called 'Purple Ronnie' who had what I presume to be paranoid schizophrenia. He was convinced there were snipers on the rooftops and that the only 'pure' water came from the well in his garden. But he was a bit odd but not a risk to anyone. In his words 'I don't take medication because when I do, I don't feel like me'.

It frustrates me that people are presumed to have NO judgement if diagnosed with a psychotic disorder. A black and white divide between compos mentis and non-compos mentis. Even I am aware that such disorders can vary from day to day. Another friend does get a medication prescribed but they decide when they NEED it. That friend saw how ill I was and was the only person who checked on me every day for weeks. He stayed over a few times and I guess I ow him my life, but for many years he was forced to take medication.

I've tried cinnarizine that antipsychotic at mid doses(blocks D2 & 5HT2A) that blocked a episode I was semi-aware of. The idea of HF psychosis is slur to quite a lot of people.

 

[4DQSAR]

What is HF psychosis?

 

[helpingout]

Can anyone tell me what they know about Lybalvi? I’ve been gaining weight on zyprexa for like 15 years. I’m pretty heavy now. I got myself off opiates and it looks like samidorphan antagonizes opioid receptors but would it diminish my ability to feel pleasure in general as well as pleasure from food?

 

[4DQSAR]

Zyprexa - Olanzapine
Lybalvi - Olanzapine/samidorphan compound medication.

I'm not terribly well read on the subject of sadimorphan but it has a pretty impressive MOR affinity of 0.052 nM but appears to be a silent agonist or mixed antagonist/partial agonist depending on where you read.

What I am aware of is all of the potent MOR antagonists I've studied can produce anhedonia. In essence blocking the reward system of the body.

Lybalvi is also a relatively new medication. I'm unclear on what the clinical advantage(s) compounding the two medicines might be. From a patent perspective, yes. But from the patients point of view, no. My concern is that sandimorphan appears to be a repurposed medicine. It's use has been investigated for treatment of substance misuse which MAY suggest that blocking the reward system is HOW it reduces food consumption. I don't know how you feel about pottentially losing that reward and possibly other natural rewards.

This is really something you need to discuss with a specialist but I suggest you ask if there might be other medicines that might help you to control your weight. I say this because if you ask about a specific medication, the specialist is unlikely to outline the possibly cheaper, possibly better and/or possibly more appropriate options.

Sorry to take up so much space saying so little. But I hope I outlined how it appears to control weight.

 

[helpingout]

Zyprexa - Olanzapine
Lybalvi - Olanzapine/samidorphan compound medication.

I'm not terribly well read on the subject of sadimorphan but it has a pretty impressive MOR affinity of 0.052 nM but appears to be a silent agonist or mixed antagonist/partial agonist depending on where you read.

What I am aware of is all of the potent MOR antagonists I've studied can produce anhedonia. In essence blocking the reward system of the body.

Lybalvi is also a relatively new medication. I'm unclear on what the clinical advantage(s) compounding the two medicines might be. From a patent perspective, yes. But from the patients point of view, no. My concern is that sandimorphan appears to be a repurposed medicine. It's use has been investigated for treatment of substance misuse which MAY suggest that blocking the reward system is HOW it reduces food consumption. I don't know how you feel about pottentially losing that reward and possibly other natural rewards.

This is really something you need to discuss with a specialist but I suggest you ask if there might be other medicines that might help you to control your weight. I say this because if you ask about a specific medication, the specialist is unlikely to outline the possibly cheaper, possibly better and/or possibly more appropriate options.

Sorry to take up so much space saying so little. But I hope I outlined how it appears to control weight.

You did well and I appreciate your input. I’m just going to bite the bullet and start exercising, taking cold showers, and keeping up with a healthy diet. I’m eating yogurt for breakfast, two eggs and avocado for lunch, cashews and cheese for snack, and for dinner grains and a rotating meat item. I’m doing pretty good on it and I do think my weight is coming down. At least I feel like it’s coming down. But I do need to begin exercising because my weight is at a point where I’m really unhealthy, blood pressure is up, cholesterol. Etc. it’s time to make a change.

 

[bigjackaal96]

What is HF psychosis?

When their literally told No AP's despite having voices & more because the Doctor/nurses, Basically they act more like someone one 450 ~ 600mg DXM acting chill. It can get lovecraftian since they discovered in LF cases the D2 blockers ruin the subconscious leading to them having moments where It takes over & lash out, The MRI shows areas that have black holes near the brain centre.

 

[aokorn]

When I once spoke to my psychiatrist and asked her how psychotropic drugs (including antidepressants) work, she told me that they only work if they have something to work on.

Therefore, someone who is mentally 'healthy' only feels the side effects of the drug.

 

[4DQSAR]

When their literally told No AP's despite having voices & more because the Doctor/nurses, Basically they act more like someone one 450 ~ 600mg DXM acting chill. It can get lovecraftian since they discovered in LF cases the D2 blockers ruin the subconscious leading to them having moments where It takes over & lash out, The MRI shows areas that have black holes near the brain centre.

Forgive my ignorance - but I'm unfamiliar with the acronym AP,

I am guessing based on the rest of your response that these are patients who may display some of the symptoms of a psychotic disorder but the cause isn't due to the chemical imbalances normally associated with such disorders.

It's interesting that you mentioned DXM. Now it's not a compound often misused in the UK but it's my understanding that it acts as an NMDA antagonist,

Well, it's been noted that there are a sub-set of people who appear to have normally functioning dopamine pathways but who, for some as yet unexplained reason(s), have low levels of NMDA. Decades ag tests ofcerebrospinal fluid showed elevated DOPAC (dopamine metaboliite) and/or depressed levels of NMDA.

Eli-Lilly actually developed a class of NMDA antagonists and it proved to be very effective in some, totally ineffective in others. Medical ethics has changed so it wasn't possible to conclusively prove that the subset of pateints who ONLY had suppressed NMDA and so overall, the new medication showed mixed results and research was cancelled.

I think it important to listen to people who suffer such disorders as they are the ones who best understand what they are experiencing. But my experience has been that the very first question a psychiatrist will ask is 'do you hear voices' and if the response is 'yes', they deem a person incapable of making infosmed decisions on the treatment THEY want.

 

[ccassa]

I didn’t take it for psychosis but cariprazine I had a love hate relationship with. It was great for motivation and extremely effective at increasing libido surprisingly yet the downsides were increasing aggression and it got bad. Maybe a bit of akathesia. But man sometimes I think about trialing a lower dose though I was on the starter dose.

Was looking for Vraylar in the thread, yeah. Atypical antipsychotic. I’m on 1.5mg add on to my 20mg escitalopram and it’s been wonders (almost a month now so cross your fingers for me good things continue)!

 

[ccassa]

Forgive my ignorance - but I'm unfamiliar with the acronym AP,

I am guessing based on the rest of your response that these are patients who may display some of the symptoms of a psychotic disorder but the cause isn't due to the chemical imbalances normally associated with such disorders.

It's interesting that you mentioned DXM. Now it's not a compound often misused in the UK but it's my understanding that it acts as an NMDA antagonist,

Well, it's been noted that there are a sub-set of people who appear to have normally functioning dopamine pathways but who, for some as yet unexplained reason(s), have low levels of NMDA. Decades ag tests ofcerebrospinal fluid showed elevated DOPAC (dopamine metaboliite) and/or depressed levels of NMDA.

Eli-Lilly actually developed a class of NMDA antagonists and it proved to be very effective in some, totally ineffective in others. Medical ethics has changed so it wasn't possible to conclusively prove that the subset of pateints who ONLY had suppressed NMDA and so overall, the new medication showed mixed results and research was cancelled.

I think it important to listen to people who suffer such disorders as they are the ones who best understand what they are experiencing. But my experience has been that the very first question a psychiatrist will ask is 'do you hear voices' and if the response is 'yes', they deem a person incapable of making infosmed decisions on the treatment THEY want.

Yes, AP = antipsychotics.

 

[Conky]

Forgive my ignorance - but I'm unfamiliar with the acronym AP,

I am guessing based on the rest of your response that these are patients who may display some of the symptoms of a psychotic disorder but the cause isn't due to the chemical imbalances normally associated with such disorders.

It's interesting that you mentioned DXM. Now it's not a compound often misused in the UK but it's my understanding that it acts as an NMDA antagonist,

Well, it's been noted that there are a sub-set of people who appear to have normally functioning dopamine pathways but who, for some as yet unexplained reason(s), have low levels of NMDA. Decades ag tests ofcerebrospinal fluid showed elevated DOPAC (dopamine metaboliite) and/or depressed levels of NMDA.

Eli-Lilly actually developed a class of NMDA antagonists and it proved to be very effective in some, totally ineffective in others. Medical ethics has changed so it wasn't possible to conclusively prove that the subset of pateints who ONLY had suppressed NMDA and so overall, the new medication showed mixed results and research was cancelled.

I think it important to listen to people who suffer such disorders as they are the ones who best understand what they are experiencing. But my experience has been that the very first question a psychiatrist will ask is 'do you hear voices' and if the response is 'yes', they deem a person incapable of making infosmed decisions on the treatment THEY want.

How has medical ethics changed? Most people on psychiatric meds probably didn't give informed consent to the prescriber. The doctors aren't educating patients about the common adverse effects. Totally unethical and they get away with it.

 

[bigjackaal96]

Well, it's been noted that there are a sub-set of people who appear to have normally functioning dopamine pathways but who, for some as yet unexplained reason(s), have low levels of NMDA. Decades ag tests ofcerebrospinal fluid showed elevated DOPAC (dopamine metaboliite) and/or depressed levels of NMDA.

Because NMDA antagonism can act exictory in the same A2A & A1 antagonism can. The Glutamate theory for Autism & Psychosis seems to imply It a 2nd brain receptor/neuron complex since the 600 IQ moments are from having a shit ton of Neurons/connections living of very high D2 which dosen't kill them. Also there even strong data that advanced Canine humanoids & other aliens that NMDA as a Inhitbtory complex Is common.

Because why aren't there any shrooms & plants that have PCP & Ketamine teir Dissos?.

 

[dopamimetic]

she told me that they only work if they have something to work on.

Yeah, but even then they can fail. I had psychosis from chronic sleep deprivation and drug overuse (dissos, stims, opiates). Heard voices and screams in white noise and had fluent conversations with the bathroom sink. No visuals, just auditorial stuff and thoughts but most of the time I was semi aware of that stuff happened only in my mind. Tried what felt like 10 different antipsychotics and they all failed, most didn't do shit besides inducing anhedonia and akathisia, aripiprazole even made the whispers louder. I recovered upon abstinence without medication, thankfully, but this episode left me scared - what should I do if that shit would recurrent and nothing works yet the docs force you to continue taking the drugs of they'd admit you to inpatient ward if shit hits the fan. My mother has schizophrenia and I think science tells there is a chance that this disorder is inherited. But I'm 38 now and nothing more.

Recently read that there is a new, non-dopaminergic antipsychotic in the pipeline which works by antagonizing TAAR1 (if my memory serves me right) and should be devoid of antidopaminergic side effects.

 

[4DQSAR]

Yes, AP = antipsychotics.

Ah, OK. I guess I'm showing my age when I'm more familiar with the older term.

I can't speak for anywhere else but in the UK at least, medical ethics have change in the form of patients no longer being forced to take a medication. Go back a few decades and even people who posed no immediate threat to themselves or others were given dpot injections of APs without the option.