The Famous Cyproheptadine Rebound

[TheCedar1]

keeping serotonin low？Isn't that the purpose of Cypro? What else should I do?

Cypro is a serotonin receptor antagonist, meaning it prevents serotonin from binding, it doesn't reduce the level of serotonin you have, hence why if you block the receptors but don't reduce your serotonin, that serotonin will rebind to its receptors, which would just restore the same symptoms. You need to take cypro with something that lowers serotonin so that your PSSD is cured

I think Haidut has a product that reduces brain serotonin levels, don't know the name unfortunately

 

[tommyg130]

Cypro is just like aspirin, antibiotics, emodin, and acetazolamide. They're wonderful chemicals to rescue the faulty metabolism short-term, but you should definitely do them in cycles. Long term usage with any drugs will have unattended/undesirable consequences, even good drugs.

Might try upping you're potassium and taking vitamin E, they both assist in expelling excess water. Potassium via making the heart pump more efficiently, and vitamin E via lowering prolactin (which is known to cause edema).

Hey , how would vitamin E which lowers prolactin cause edema ? I’m trying to grasp how lowering prolactin would cause edema in any way ? Also wondering if Vitamin E Needs to be cyclical like the others you mentioned ? Wouldn’t think so right ?!

 

[TheCedar1]

Hey , how would vitamin E which lowers prolactin cause edema ? I’m trying to grasp how lowering prolactin would cause edema in any way ? Also wondering if Vitamin E Needs to be cyclical like the others you mentioned ? Wouldn’t think so right ?!

He said that prolactin causes Edema, and that taking vitamin E would reduce prolactin, and cure you of edema.

 

[Jessie]

Hey , how would vitamin E which lowers prolactin cause edema ? I’m trying to grasp how lowering prolactin would cause edema in any way ? Also wondering if Vitamin E Needs to be cyclical like the others you mentioned ? Wouldn’t think so right ?!

No, I mentioned vitamin E because it should assist in expelling excess water. Because high prolactin is known to cause edema.

 

[AVTISTICVS]

I have paradoxical reactions to most substances. Cyproheptadine included. As with most of you, I do get a significant effect from this medication. Short of psychedelics, it produces the most significant changes to my perception to date.

However, my timeline is different. When I take this substance at night, I wake up to feeling “fixed” the very next day. This effect lasts 2-3 days depending on the dose. As my hepatic metabolism is normal, it would stand to reason data from my usage might provide something new to help close this gap.

I have been experimenting with substances have that binding profiles almost exactly the same in targets & affinity but with one difference. Tonight I will be taking Chlorphenamine. The approach here being that the only thing similar to cypro is that it is a first generation H1 inverse agonist that crosses the blood-brain barrier readily. Should I share the same mechanism providing the change we all experience, I should in time be able to filter out the correct mechanism.

 

[Lokzo]

I have paradoxical reactions to most substances. Cyproheptadine included. As with most of you, I do get a significant effect from this medication. Short of psychedelics, it produces the most significant changes to my perception to date.

However, my timeline is different. When I take this substance at night, I wake up to feeling “fixed” the very next day. This effect lasts 2-3 days depending on the dose. As my hepatic metabolism is normal, it would stand to reason data from my usage might provide something new to help close this gap.

I have been experimenting with substances have that binding profiles almost exactly the same in targets & affinity but with one difference. Tonight I will be taking Chlorphenamine. The approach here being that the only thing similar to cypro is that it is a first generation H1 inverse agonist that crosses the blood-brain barrier readily. Should I share the same mechanism providing the change we all experience, I should in time be able to filter out the correct mechanism.

That is awesome, thanks for experimenting for us! I am very excited to see how you respond to Chlorphenamine.

 

[AVTISTICVS]

That is awesome, thanks for experimenting for us! I am very excited to see how you respond to Chlorphenamine.

Chlorphenamine: No effect. Next is Hydroxyzine. Waiting for it to arrive. Very similar binding profile as Cypro. Weaker affinity at D2 and 5HT2A but still strong enough to be apparent if either are the mechanism at hand.

Differences: No 5HT1A binding. No effect on cortisol.

I’ve tried Metergoline: No effect. Antagonist at 5HT2A with strong affinity. 5HT1A Full agonist (mock 5HT1A sensitization)

I’ve tried Lisuride: 5HT1A Agonist. 5HT2A Agonist (Mock sensitization). Though it also is an antagonist at the 5HT2A-mGlu2. I’ve separated and targeted mGlu2 with Sarcosine and Fascoracetam. No effect. Psychedelics hit this and produce the same benefit though.

Data is pointing to Cortisol. I also have Hydrocortisone oral tablets on the way. In the meantime I will look for a potent substance that lowers cortisol like Cypro. It should be noted that Cypro is so potent for lowering cortisol that it is sometimes used as a treatment for Cushing’s disease.

I know the main theory here is 5HT2A antagonism. I thought that for a while. On top of my experiments not pointing towards it, the onset of action for 5HT2A antagonism is short. The way It’s typically used for PSSD is ingesting a couple of hours before coitus. I can confirm pro sexual effects within this range. It is also documented to have substantially diminished effects on CNS after only 8 hours. With that in mind, I would expect rapid re-sensitization of 5HT receptors would be expected to occur much quicker than the 4 days and it to be more gradual most people are seeing. D2 even pickier. Though I couldn’t comment on a timeline.

 

[Lokzo]

Chlorphenamine: No effect. Next is Hydroxyzine. Waiting for it to arrive. Very similar binding profile as Cypro. Weaker affinity at D2 and 5HT2A but still strong enough to be apparent if either are the mechanism at hand.

Differences: No 5HT1A binding. No effect on cortisol.

I’ve tried Metergoline: No effect. Antagonist at 5HT2A with strong affinity. 5HT1A Full agonist (mock 5HT1A sensitization)

I’ve tried Lisuride: 5HT1A Agonist. 5HT2A Agonist (Mock sensitization). Though it also is an antagonist at the 5HT2A-mGlu2. I’ve separated and targeted mGlu2 with Sarcosine and Fascoracetam. No effect. Psychedelics hit this and produce the same benefit though.

Data is pointing to Cortisol. I also have Hydrocortisone oral tablets on the way. In the meantime I will look for a potent substance that lowers cortisol like Cypro. It should be noted that Cypro is so potent for lowering cortisol that it is sometimes used as a treatment for Cushing’s disease.

I know the main theory here is 5HT2A antagonism. I thought that for a while. On top of my experiments not pointing towards it, the onset of action for 5HT2A antagonism is short. The way It’s typically used for PSSD is ingesting a couple of hours before coitus. I can confirm pro sexual effects within this range. It is also documented to have substantially diminished effects on CNS after only 8 hours. With that in mind, I would expect rapid re-sensitization of 5HT receptors would be expected to occur much quicker than the 4 days and it to be more gradual most people are seeing. D2 even pickier. Though I couldn’t comment on a timeline.

This data is invaluable, thanks so much man. I did try 10-MEO-Haramalan too a while ago, but that made me a lot WORSE and made me worse for a long time. I didn't like it. Did you ever try St John's Wort Remotiv brand?

 

[AVTISTICVS]

This data is invaluable, thanks so much man. I did try 10-MEO-Haramalan too a while ago, but that made me a lot WORSE and made me worse for a long time. I didn't like it. Did you ever try St John's Wort Remotiv brand?

You’re welcome. I hope the information eventually leads to a solid conclusion.

I’ve never taken 10-Meo. I didn’t know a 10 variant of existed.

I haven’t taken that brand. But I have experimented with a standalone hypericin extracts and a standalone hyperforin extract. I started with the hypericin extract because of the receptor upregulation on 5HT receptors. Once it kicked in I felt terrible every time I took it.

The Hyperforin extract (NDSRI) I had positive effects from. I didnt trial it for too long after effects appeared as I had many substances in queue to try. I don’t know which substance in ST.Johns does it but if I remember correctly it lowered cortisol levels significantly in rat brains.

I can also say that 2mg of cypro begins its positive effects almost exactly 14 hours later every time. I took 1mg at bed last night at midnight and woke up at 10am with some positive effects already.

 

[AVTISTICVS]

You can ignore my comment on cortisol. This was incorrect. My original theory (seen here) Link was correct. I feel confident that the receptors involved in my benefit and your benefit are the same. But with the issue in my catecholamine balance I react at a different period. Here is why it works for me and what I've determined.
I have Schizoid personality disorder. This was extremely difficult to nail down because I don't have delusions (Lack of dopamine overactivity) Frequently seen in schizophrenics is an imbalance between 5HT2A receptors and 5HT1A receptors. 5HT2A receptors are lower in number and overly sensitized. 5HT1A receptors are high in number and overly de-sensitized. This is part of why excess pre-synaptic glutamate release and altered dopamine release is seen in schizophrenics.

Cyproheptadine takes between 14 hours for 2mg before it starts working for me and works for 3 or 4 days depending on the dose. The reason is that is takes time for the 5HT1A receptor to stop being antagonized while simultaneously still antagonizing 5HT2A receptors. Both sub-receptors are antagonized strongly but there is a significant difference in binding affinities. Additionally, 5HT1A agonism by itself does nothing. 5HT2A Antagonism does something by itself. There is a significant change in olfactory senses. But with the 5HT1A still be antagonized the effect is minimal in comparison.

Now. The question: What is the mechanism of action by which you are corrected four days later? My theory is that it is exact same reason but since we need different balances it takes longer. Four days later (at the doses typically posted) 5HT2A antagonism will have stopped along with every other receptor target from the drug. The difference is that our 5HT2A receptors will have down-regulated. (There is also the possibility that there is slight upregulation of autoreceptors. I can't commit to that with confidence though) Ironically, though I said cortisol is not the reason Cypro causes these effects, (Plenty of studies show cortisol effect is very short lived) it may actually be an option for those with somewhat normal brain chemistry to rebalance the receptors in the same way Cypro does by correcting cortisol levels. Chronically elevated cortisol causes exactly the issue that cyproheptadine is fixing. Elevated cortisol causes 5HT2A upregulation and 5HT1A downregulation.

 

[AspiringSage]

This thread is relevant to my interests

 

[Lokzo]

You can ignore my comment on cortisol. This was incorrect. My original theory (seen here) Link was correct. I feel confident that the receptors involved in my benefit and your benefit are the same. But with the issue in my catecholamine balance I react at a different period. Here is why it works for me and what I've determined.
I have Schizoid personality disorder. This was extremely difficult to nail down because I don't have delusions (Lack of dopamine overactivity) Frequently seen in schizophrenics is an imbalance between 5HT2A receptors and 5HT1A receptors. 5HT2A receptors are lower in number and overly sensitized. 5HT1A receptors are high in number and overly de-sensitized. This is part of why excess pre-synaptic glutamate release and altered dopamine release is seen in schizophrenics.

Cyproheptadine takes between 14 hours for 2mg before it starts working for me and works for 3 or 4 days depending on the dose. The reason is that is takes time for the 5HT1A receptor to stop being antagonized while simultaneously still antagonizing 5HT2A receptors. Both sub-receptors are antagonized strongly but there is a significant difference in binding affinities. Additionally, 5HT1A agonism by itself does nothing. 5HT2A Antagonism does something by itself. There is a significant change in olfactory senses. But with the 5HT1A still be antagonized the effect is minimal in comparison.

Now. The question: What is the mechanism of action by which you are corrected four days later? My theory is that it is exact same reason but since we need different balances it takes longer. Four days later (at the doses typically posted) 5HT2A antagonism will have stopped along with every other receptor target from the drug. The difference is that our 5HT2A receptors will have down-regulated. (There is also the possibility that there is slight upregulation of autoreceptors. I can't commit to that with confidence though) Ironically, though I said cortisol is not the reason Cypro causes these effects, (Plenty of studies show cortisol effect is very short lived) it may actually be an option for those with somewhat normal brain chemistry to rebalance the receptors in the same way Cypro does by correcting cortisol levels. Chronically elevated cortisol causes exactly the issue that cyproheptadine is fixing. Elevated cortisol causes 5HT2A upregulation and 5HT1A downregulation.

Well firstly, hats off to you for putting the meticulous effort to work through this. It's been an ongoing quest, for a number of years to understand what Cypro does to my brain. I keep saying... If I can find a way to MIMIC the effect of a cyproheptadine rebound, that would be the most IDEAL state of being in my opinion. 4-5 days after a single dose of cypro ALWAYS elicits this incredible feeling, that if I were to be honest, makes me feel like God. Verbal fluency, ZERO anxiety, ultra confidence, ultra clear headed, energetic, outgoing, fun, sexually excited by all types of women, pleasure responses back online, NO more blunted emotions feeling.
So to challenge your theory, I would say that I am NOT schizoid personality type, because I still have great relationships/friendships, I am not a loner, I crave social connections etc.

In order to determine what is going on, I have a few experiments lined up.
1. Oxytocin nasal spray
2. Pizotifen
3. Some other 5-HT2A Antagonist anti-histamine
4. Maybe Buspirone? Scared of permanent destruction of my brain though.
5. If your theory of 5-HT2A being too up-regulated, it makes me tempted to start microdosing Psilocybin, although I fear this will destroy my work/career related goals and focus more so on NATURE/introspection. I also fear it permanently messing up my already VERY high functioning/high productivity brain.
I would like to add, that in my experience, there is a homeopathic remedy called Phosphorus which can mimic the effects of cypro identically for me. It's used to treat INDIFFERENCE, APATHY, Anhedonia etc. I have used it probably now over 15 times in my lifetime, potency 30c, and each time it also feels like it restores the spark, almost like it igniting my cortisol back up? I tested EXTREMELY low metabolized cortisol on the DUTCH test btw... And I also crave salt like crazy, and have very low aldosterone.

 

[redsun]

Well firstly, hats off to you for putting the meticulous effort to work through this. It's been an ongoing quest, for a number of years to understand what Cypro does to my brain. I keep saying... If I can find a way to MIMIC the effect of a cyproheptadine rebound, that would be the most IDEAL state of being in my opinion. 4-5 days after a single dose of cypro ALWAYS elicits this incredible feeling, that if I were to be honest, makes me feel like God. Verbal fluency, ZERO anxiety, ultra confidence, ultra clear headed, energetic, outgoing, fun, sexually excited by all types of women, pleasure responses back online, NO more blunted emotions feeling.
So to challenge your theory, I would say that I am NOT schizoid personality type, because I still have great relationships/friendships, I am not a loner, I crave social connections etc.

In order to determine what is going on, I have a few experiments lined up.
1. Oxytocin nasal spray
2. Pizotifen
3. Some other 5-HT2A Antagonist anti-histamine
4. Maybe Buspirone? Scared of permanent destruction of my brain though.
5. If your theory of 5-HT2A being too up-regulated, it makes me tempted to start microdosing Psilocybin, although I fear this will destroy my work/career related goals and focus more so on NATURE/introspection. I also fear it permanently messing up my already VERY high functioning/high productivity brain.
I would like to add, that in my experience, there is a homeopathic remedy called Phosphorus which can mimic the effects of cypro identically for me. It's used to treat INDIFFERENCE, APATHY, Anhedonia etc. I have used it probably now over 15 times in my lifetime, potency 30c, and each time it also feels like it restores the spark, almost like it igniting my cortisol back up? I tested EXTREMELY low metabolized cortisol on the DUTCH test btw... And I also crave salt like crazy, and have very low aldosterone.

Consider a racetam to the list. Aniracetam may be good to try to explore the acetylcholine angle. But there are others as well. It just need to be taken with choline.

What do you mean phosphorus? Are you talking about the actual mineral or it just the name of the product?

I assuming you have tried potassium supplementation before? Since research shows it directly stimulates ACTH and also aldosterone.

 

[AVTISTICVS]

Well firstly, hats off to you for putting the meticulous effort to work through this. It's been an ongoing quest, for a number of years to understand what Cypro does to my brain. I keep saying... If I can find a way to MIMIC the effect of a cyproheptadine rebound, that would be the most IDEAL state of being in my opinion. 4-5 days after a single dose of cypro ALWAYS elicits this incredible feeling, that if I were to be honest, makes me feel like God. Verbal fluency, ZERO anxiety, ultra confidence, ultra clear headed, energetic, outgoing, fun, sexually excited by all types of women, pleasure responses back online, NO more blunted emotions feeling.
So to challenge your theory, I would say that I am NOT schizoid personality type, because I still have great relationships/friendships, I am not a loner, I crave social connections etc.

In order to determine what is going on, I have a few experiments lined up.
1. Oxytocin nasal spray
2. Pizotifen
3. Some other 5-HT2A Antagonist anti-histamine
4. Maybe Buspirone? Scared of permanent destruction of my brain though.
5. If your theory of 5-HT2A being too up-regulated, it makes me tempted to start microdosing Psilocybin, although I fear this will destroy my work/career related goals and focus more so on NATURE/introspection. I also fear it permanently messing up my already VERY high functioning/high productivity brain.
I would like to add, that in my experience, there is a homeopathic remedy called Phosphorus which can mimic the effects of cypro identically for me. It's used to treat INDIFFERENCE, APATHY, Anhedonia etc. I have used it probably now over 15 times in my lifetime, potency 30c, and each time it also feels like it restores the spark, almost like it igniting my cortisol back up? I tested EXTREMELY low metabolized cortisol on the DUTCH test btw... And I also crave salt like crazy, and have very low aldosterone.

Thanks. I've tested substance after substance and this was the first one that made me feel human. In regards to the Schizoid, my thinking is that your balance (and those that benefit from it) between 5ht2a and 5ht1a needs a fairly minimal adjustment. For me massive 5ht2a antagonism is needed because of the massive imbalance. For others that massive antagonism isn't needed. At least that's what I think it happening here.

If your cortisol is low then anti-histamine may help depending on why your cortisol is low. Elevated histamine causes adrenals to make cortisol. If it's a stimulation issue you'd want histamine higher. Though there are much better ways to raise it. Licorice is an uptake inhibitor. It's has weak pro estrogen receptor activation but cortisol also lowers your estrogen levels. Only way I could see an anti-histamine being beneficial is if you have secondary adrenal insufficiency from long term glucocorticoid "abuse" or something and are giving your adrenals a temporary break (glucocorticoids also downregulate 5HT1A btw). That being said have you had ACTH, aldosterone, DHEA tested? Also gluccocorticoids extend to stuff like Nasacort, ie allergy meds.
Pizotifen might be a decent choice depending on the binding affinity. I never could find the binding affinity for it though. Skip the oxytocin. Even if it did produce the feeling you're looking for that a downstream effect from 5HT2A, 5HT1A. Buspar upregulates 5HT2A. Not what you are looking for.
Pscilocybin Is the only drug I can fully get behind. Some people find benefits microdosing but long term use isn't good for your brain chemistry. Mega doses are where the benefits are at in my opinion. I'm blown away every time I do them. Though I wouldn't suggest them for your Cyproheptadine goals.
What I would do is try a St Johns wort extract. Start with one high in hypericin (upregulates 5ht1a,2a / 2a is fine temporarily). Then add in a hyperforin heavy one (perika) and experiment with 1/3 or 2/3 between the types. After 3 or 4 weeks try cyproheptadine again but like a 1/4 of your normal dose. Or an extremely small dose of mirtzapine or mianserin.

 

[AVTISTICVS]

Consider a racetam to the list. Aniracetam may be good to try to explore the acetylcholine angle. But there are others as well. It just need to be taken with choline.

What do you mean phosphorus? Are you talking about the actual mineral or it just the name of the product?

I assuming you have tried potassium supplementation before? Since research shows it directly stimulates ACTH and also aldosterone.

Aniracetam is a positive allosteric modulator of AMPA. Usually that kind of behavior will also cause NMDA to be upregulated though I haven't looked for this on Aniracetam specifically. Racetams are pretty awesome and would probably provide benefit. Though I doubt NMDA or AMPA is the issue here. They use Glycine and glutamate. I doubt he is deficient in either. Additionally, if 5HT1A has been downregulated then there is a chance inhibition of NMDA Ca2+ currents are already lacking.

 

[redsun]

Aniracetam is a positive allosteric modulator of AMPA. Usually that kind of behavior will also cause NMDA to be upregulated though I haven't looked for this on Aniracetam specifically. Racetams are pretty awesome and would probably provide benefit. Though I doubt NMDA or AMPA is the issue here. They use Glycine and glutamate. I doubt he is deficient in either. Additionally, if 5HT1A has been downregulated then there is a chance inhibition of NMDA Ca2+ currents are already lacking.

It does potentiate acetylcholine release but probably piracetam which does upregulate acetylcholine receptors may make more sense.

 

[InChristAlone]

Have you ever tried an MAOI? High T men tend to have very active MAO which causes low serotonin, dopamine and noradrenaline.

 

[AVTISTICVS]

Have you ever tried an MAOI? High T men tend to have very active MAO which causes low serotonin, dopamine and noradrenaline.

I figure this question is aimed at Lokzo but I’m going to answer since I know my results for data’s sake.

I personally have excess serotonin. I also have the COMT mutation that would make it the least efficient. Whether that mutation is actually being expressed and the reason for my excess serotonin I don’t know.

My Test averages around 900 ng/dL
My Estradiol averages around 20 pg/mL

I generally feel better when my E2 is raised. When it swings on the lower variation range my joints hurts, my sex drive is gone, I feel even more flat.

 

[AVTISTICVS]

Received my labs. Cortisol and ACTH is out of range high. Not quite Cushings range but up there. And I didnt get blood drawn till almost 11am.

 

[chompie]

Received my labs. Cortisol and ACTH is out of range high. Not quite Cushings range but up there. And I didnt get blood drawn till almost 11am.

What's your BP and blood sugar doing?