The Famous Cyproheptadine Rebound

[redsun]

Very interesting thank you.

Even though Dr. Peat warns against iodine as toxic to the thyroid? At one point on my journey i was put on iodoral and ended up with thyroiditis- my heart was literally leaping out of my chest- so a little scared to try iodine. Do you have any insight on this conflict?

I eat oysters and liver regularly so would think i am getting a good amount of zinc. those should cover my copper too as well as shrimp which i eat as well.

The citrus thing wow- i do drink a lot of OJ per Peat principles. i wonder what Dr. Peat would say about that since he is such a proponent of OJ. It would seem he would not recommend it so empathically and amply if he thought it would trigger mast cells? im open to all at this point but other than this one issue which is severe, I dont want to sacrifice my endocrine and hormone balance which are pretty remarkable- hormone levels on blood work just came back like someone 25 years old so there is good too.

Iodoral has extremely high levels of iodine which you should never take. Megadosing iodine protocols utilize selenium and myo-inositol to prevent this thyroiditis problem. Iodine is not toxic to the thyroid except in excessive quantities and when taken in such quantities need to be taken with selenium and myo-inositol. But personally I not recommend that anyways. Normal iodine intakes of around 150 mcg is not going to cause these reactions.

Treatment with Myo-Inositol and Selenium Ensures Euthyroidism in Patients with Autoimmune Thyroiditis - PubMed

Clinical evidences have highlighted the efficacy of myo-inositol and selenium in the treatment of autoimmune thyroiditis. Aim of this study was to further analyze the role of myo-inositol plus selenium (Myo-Ins-Se) in restoring a normal thyroid function of Hashimoto's patients with subclinical...

pubmed.ncbi.nlm.nih.gov

"
Clinical evidences have highlighted the efficacy of myo-inositol and selenium in the treatment of autoimmune thyroiditis. Aim of this study was to further analyze the role of myo-inositol plus selenium (Myo-Ins-Se) in restoring a normal thyroid function of Hashimoto's patients with subclinical hypothyroidism. Eighty-six patients with Hashimoto's thyroiditis having thyroid-stimulating hormone (TSH) levels between 3 and 6 mIU/L, elevated serum antithyroid peroxidase (TPOAb) and/or antithyroglobulin (TgAb), and normal free thyroxine (fT4) and free triiodothyronine (fT3) levels were enrolled in the study: one hyperthyroid subject with TSH about 0.14 μU/ml was included in this trial as a single case. Patients were assigned to receive Myo-Ins-Se. TSH, TPOAb, and TgAb levels were significantly decreased in patients treated with combined Myo-Ins-Se after 6 months of treatment. In addition, a significant fT3 and fT4 increase, along with an amelioration of their quality of life, was observed. Remarkably, TSH values of the hyperthyroid patient increased from 0.14 μU/ml up to 1.02 μU/ml, showing a complete restoration of TSH values at a normal range. In conclusion, the administration of Myo-Ins-Se is significantly effective in decreasing TSH, TPOAb, and TgAb levels, as well as enhancing thyroid hormones and personal wellbeing, therefore restoring euthyroidism in patients diagnosed with autoimmune thyroiditis."

Not everyone has mast cell issues. Some people consume citrus no problem. But if you are one of those who do, citrus is one of the worst offenders especially if you consume tons of it all day. Its like giving yourself regular doses of mast cell activators all day long. So any environmental trigger is amplified because OJ is already stimulating the mast cells constantly. You don't need to consume citrus to be healthy. There are non-citrus fruits that are not mast cell activators and cause much less histamine reactions or none at all.

I would try the conservative approach of trying just no citrus for a short time. You may not need anything else but if so you can experiment with appropriate doses of iodine, 150 mcg (not milligrams) in the morning.

This link has a list of fruits that are more tolerable that you can try instead:

Low Histamine Diet | Full Histamine Intolerance Foods List

See 187 foods to eat and avoid on a low histamine diet. Start improving histamine intolerance symptoms in just 2 weeks using this low histamine foods list.

www.factvsfitness.com

I know we discussed about iron quite awhile back. Did you ever get your iron status tested?

 

[Advocate2021]

Iodoral has extremely high levels of iodine which you should never take. Megadosing iodine protocols utilize selenium and myo-inositol to prevent this thyroiditis problem. Iodine is not toxic to the thyroid except in excessive quantities and when taken in such quantities need to be taken with selenium and myo-inositol. But personally I not recommend that anyways. Normal iodine intakes of around 150 mcg is not going to cause these reactions.

Treatment with Myo-Inositol and Selenium Ensures Euthyroidism in Patients with Autoimmune Thyroiditis - PubMed

Clinical evidences have highlighted the efficacy of myo-inositol and selenium in the treatment of autoimmune thyroiditis. Aim of this study was to further analyze the role of myo-inositol plus selenium (Myo-Ins-Se) in restoring a normal thyroid function of Hashimoto's patients with subclinical...

pubmed.ncbi.nlm.nih.gov

"
Clinical evidences have highlighted the efficacy of myo-inositol and selenium in the treatment of autoimmune thyroiditis. Aim of this study was to further analyze the role of myo-inositol plus selenium (Myo-Ins-Se) in restoring a normal thyroid function of Hashimoto's patients with subclinical hypothyroidism. Eighty-six patients with Hashimoto's thyroiditis having thyroid-stimulating hormone (TSH) levels between 3 and 6 mIU/L, elevated serum antithyroid peroxidase (TPOAb) and/or antithyroglobulin (TgAb), and normal free thyroxine (fT4) and free triiodothyronine (fT3) levels were enrolled in the study: one hyperthyroid subject with TSH about 0.14 μU/ml was included in this trial as a single case. Patients were assigned to receive Myo-Ins-Se. TSH, TPOAb, and TgAb levels were significantly decreased in patients treated with combined Myo-Ins-Se after 6 months of treatment. In addition, a significant fT3 and fT4 increase, along with an amelioration of their quality of life, was observed. Remarkably, TSH values of the hyperthyroid patient increased from 0.14 μU/ml up to 1.02 μU/ml, showing a complete restoration of TSH values at a normal range. In conclusion, the administration of Myo-Ins-Se is significantly effective in decreasing TSH, TPOAb, and TgAb levels, as well as enhancing thyroid hormones and personal wellbeing, therefore restoring euthyroidism in patients diagnosed with autoimmune thyroiditis."

Not everyone has mast cell issues. Some people consume citrus no problem. But if you are one of those who do, citrus is one of the worst offenders especially if you consume tons of it all day. Its like giving yourself regular doses of mast cell activators all day long. So any environmental trigger is amplified because OJ is already stimulating the mast cells constantly. You don't need to consume citrus to be healthy. There are non-citrus fruits that are not mast cell activators and cause much less histamine reactions or none at all.

I would try the conservative approach of trying just no citrus for a short time. You may not need anything else but if so you can experiment with appropriate doses of iodine, 150 mcg (not milligrams) in the morning.

This link has a list of fruits that are more tolerable that you can try instead:

Low Histamine Diet | Full Histamine Intolerance Foods List

See 187 foods to eat and avoid on a low histamine diet. Start improving histamine intolerance symptoms in just 2 weeks using this low histamine foods list.

www.factvsfitness.com

I know we discussed about iron quite awhile back. Did you ever get your iron status tested?

Thank you - the no OJ experiment sounds feasible although i would have to study regarding how to replace nutritionally. i note the no dairy on that list - that would be tough since that is a huge part of my diet. hoping the no OJ experiment works. Woe- if ive been poisoining myself all these years with OJ that would be something wouldnt it? And ive had this convo with Dr. Peat for 15 years. and of course i have a stock of Organic OJ but luckily the dates are in March so will still be good if it turns out that is not the issue lol.

i believe i am waiting for bloodwork on iron that was left out by mistake the first draw so had to go back Friday to get it. since i eat liver and oysters regularly cannot imagine i would be low and have never been low in the past but will see when bloodwork comes back.

Thank you!!

 

[redsun]

Thank you - the no OJ experiment sounds feasible although i would have to study regarding how to replace nutritionally. i note the no dairy on that list - that would be tough since that is a huge part of my diet. hoping the no OJ experiment works. Woe- if ive been poisoining myself all these years with OJ that would be something wouldnt it? And ive had this convo with Dr. Peat for 15 years. and of course i have a stock of Organic OJ but luckily the dates are in March so will still be good if it turns out that is not the issue lol.

i believe i am waiting for bloodwork on iron that was left out by mistake the first draw so had to go back Friday to get it. since i eat liver and oysters regularly cannot imagine i would be low and have never been low in the past but will see when bloodwork comes back.

Thank you!!

OJ is not poison though it may feel like your poisoned. Its just the unfortunate reality some people cannot do citrus.

No read carefully. Dairy that is not fermented or barely fermented is not a problem. But something like parmesan for example which is aged heavily is a problem.

 

[Advocate2021]

OJ is not poison though it may feel like your poisoned. Its just the unfortunate reality some people cannot do citrus.

No read carefully. Dairy that is not fermented or barely fermented is not a problem. But something like parmesan for example which is aged heavily is a problem.

i know - i was being dramatic. and while this makes sense and could be making things worse for me, i dont think its causing the issue. my allergies started basically out of the womb and were still terrible even when i was subsisting on meat and vegetables- they definitely pre date citrus and food high in histamine consumption; but i could see how the citrus could be exacerbating. I believe any mast cell abnormality i have most likely stems from being born to a mother who was severely out of hormonal balance (my mother also never got her period and at 18 was put on very strong hormones- God knows what but high estrogen for sure. She said she gained 50 lbs in a month and grew hair all over her body when she went off to college; so i suspect mega estrogen. she got pregnant with me within a year or two of that; so i really think i was probably exposed to suboptimal hormones in the womb,

i also think childhood vaccines play a role in light of what i have learned about vaccines and the damage they cause. Anaphalaxis and allergies are an effect apparently. but i certainly dont want to make myself worse and i still believe even the damage form these other factors can be repaired or greatly mitigated. Dr. Peat really did not believe anything was irreparable and that by changing the environment of the organism, health can be restored. so i am optimisitc and also incredibly grateful for the health that i do have in all other respects.

 

[AVTISTICVS]

ive tried the nasal spays in the past with not much effect. I here amazing things about quercetin but Dr. Peat didnt like it when i asked him if i recall. but again, open at this point. pretty sure ive taken it in the past though.

Did you take the sprays for at least a week? It takes time to kick in.

 

[redsun]

i know - i was being dramatic. and while this makes sense and could be making things worse for me, i dont think its causing the issue. my allergies started basically out of the womb and were still terrible even when i was subsisting on meat and vegetables- they definitely pre date citrus and food high in histamine consumption; but i could see how the citrus could be exacerbating. I believe any mast cell abnormality i have most likely stems from being born to a mother who was severely out of hormonal balance (my mother also never got her period and at 18 was put on very strong hormones- God knows what but high estrogen for sure. She said she gained 50 lbs in a month and grew hair all over her body when she went off to college; so i suspect mega estrogen. she got pregnant with me within a year or two of that; so i really think i was probably exposed to suboptimal hormones in the womb,

i also think childhood vaccines play a role in light of what i have learned about vaccines and the damage they cause. Anaphalaxis and allergies are an effect apparently. but i certainly dont want to make myself worse and i still believe even the damage form these other factors can be repaired or greatly mitigated. Dr. Peat really did not believe anything was irreparable and that by changing the environment of the organism, health can be restored. so i am optimisitc and also incredibly grateful for the health that i do have in all other respects.

Well I never said it causes the issue. Its related to genetics and is of course related to hormones and many other things. There is no one reason why it happens but citrus is a known trigger so it can greatly reduce symptoms if you stop. So if you try it and it helps a lot then that's definitely a win in my book.

 

[Advocate2021]

Did you take the sprays for at least a week? It takes time to kick in.

yes many times. but what good is it if you cannot use it longterm due to the corticosteroids? that has always been a deterrent to me and i know Dr. Peat did not think they were safe due to systemic absorption.

i am looking to get to the root of my issue, not slap another bandaid on it. but i do appreciate your input and have no doubt that these products provide relief for many. im just done with treating symptoms and want to achieve optimal health and balance and this is my last puzzle piece- ive cured myself of the countless other issues i had so can really focus on this now.

 

[Tidal]

I have a few theories. Sensitization if ip3-pkc pathway is my main theory.

I’ve just trialed risperdal and can confirm that

1. My increase in smell and taste is from 5ht2a or 5ht2c antagonism.

2. I still have the above effects during the rebound. So it’s not a supersensitivity of the above and whatever is causing the rebound is less bound by Cypro than the above receptors (5ht2a only takes 6 hours to recycle). There aren’t many targets with less binding affinity between 5ht2 and receptors that simply are not affected because if the small dose we still see the rebound with.

3. It could also be something not related to receptors. Ex. Supression of Tnfa, IL6, etc.

All that being said I’m coming to the realization that I respond well to inhibitory compounds.

How do you respond to stuff like glycine, theanine, taurine?

Sensitization of muscarinic receptors or serotonin? Is there anything we can do to test or recreate this? Anything that could have beneficial effects on this pathway? I'm sure it's involved in my negative response to Myo inositol somehow as well.

Vitamin E is a protein kinase C inhibitor but it hasn't helped unfortunately.

My smell and taste are not affected.

I'm sure the immune system is involved somehow as I got an autoimmune disease at the same time fluoxetine gave me anhedonia, but I can't work out what pathways to target and how.

I was unable to catch colds for years until I took a single capsule of honokiol and caught the flu that's going around.

With my rebound I had pronounced flu symptoms which I ordinarily wouldn't get. But I have the flu now and it's not helping anything.

And those substances have no effect on me. Nothing really seems to apart from the few things I've crashed from. For example one pill of biotin was enough to cause neurogenic bladder which is similar to my stomach numbness/lack of nausea

 

[Advocate2021]

Well I never said it causes the issue. Its related to genetics and is of course related to hormones and many other things. There is no one reason why it happens but citrus is a known trigger so it can greatly reduce symptoms if you stop. So if you try it and it helps a lot then that's definitely a win in my book.

For sure and thank you so much. Started yesterday and i think i am already feeling the difference. i think whole foods will let me return my six 89 oz jugs of 365 brand organic OJ lol. ive been living in great part on OJ for the last 14 years!!! i loaded up on organic grape juice, applesauce, apple juice and some other items. i have been apparently eating all of the wrong foods! saw raisins on the list and have been eating those too as organic fruit has been in low supply- not a lot of choices. Ive been so focused on recovering from so much Big pharma poisoning and manipulation and every other issue known to man, hormones, thyroid and eating a peaty diet, i just completely overlooked such a fundamental idea. Wow- been doing such "advanced" measures and have great hormones and youthful chemistry but haven't been able to co-exist on the planet - and could be due in great part to the very healthy foods like OJ i thought were bolstering my endocrine function!! Will continue to study and fine tune; but this advice is the most helpful i have gotten here thus far and so much simpler than all of the complex supplement regimens!! Awe struck truly! Thank you!!!!

 

[redsun]

For sure and thank you so much. Started yesterday and i think i am already feeling the difference. i think whole foods will let me return my six 89 oz jugs of 365 brand organic OJ lol. ive been living in great part on OJ for the last 14 years!!! i loaded up on organic grape juice, applesauce, apple juice and some other items. i have been apparently eating all of the wrong foods! saw raisins on the list and have been eating those too as organic fruit has been in low supply- not a lot of choices. Ive been so focused on recovering from so much Big pharma poisoning and manipulation and every other issue known to man, hormones, thyroid and eating a peaty diet, i just completely overlooked such a fundamental idea. Wow- been doing such "advanced" measures and have great hormones and youthful chemistry but haven't been able to co-exist on the planet - and could be due in great part to the very healthy foods like OJ i thought were bolstering my endocrine function!! Will continue to study and fine tune; but this advice is the most helpful i have gotten here thus far and so much simpler than all of the complex supplement regimens!! Awe struck truly! Thank you!!!!

Let us know if you improve after a week.

 

[Advocate2021]

Let us know if you improve after a week.

So here is my one week update on the "low histamine" diet or so i thought. see below:

this histamine thing is very tricky. in my diligence to sub in low histamine items, i actually introduced some problematic things These bottled juices like unfiltered apple ( dr. peat did not recommend pulp due to mold risk- maybe that?),cranberry, blueberry - is it mold or histamine ? having reactions to them and my intestine has not been nearly as good since this diet change - i suspect due to whatever is in these juices to which i am allergic and also the young cheeses are not necessarily made traditionally with rennet so i dont know if im getting objectionable enzymes now? i now have to go back to Whole foods and walmart and return all these juices ( the concord grape i think may be ok and Dr. P recommended but its still in a bottle off of a shelf so?) and some of the cheese i think.

it just seems our world is completely histamine contaminated, even the apparently available" low histamine" choices due to the way they are processed and commercialized. and many of the supposedly low histamine foods are susceptible to mold. hard to know what is left to eat that is readily available in stores. must research on line and local farm sources and try to eat all fresh if possible.

My intestine has taken a dreadful turn for the worse the last week- very different from when i was drinking OJ and eating parmesan- and im still reacting to the impurities of the foods and juices despite their characterization as "low histamine", I suspect due to these other aspects I have enumerated above. I might be a little less congested not much; but seems the problematic aspects of the impurities in these items are canceling out any real progress for me thus far.

After 30 years of trial and error, i really think for me the answer is some real practitioner support and data. i found a place but its very expensive. but without knowing the underlying mechanisms, its all trial and error and ive been doing this way too long despite fixing all of my endocrinological issues., just got bloodwork back on all of that and it was impeccable- i look like the perfect female hormone and thyroid poster child based upon that with a hormone profile of a woman 30 years younger. Yet i am allergic to the planet earth. Go figure. All input welcome!-

But i continue to persist in resolving this final but insidious issue!

 

[redsun]

So here is my one week update on the "low histamine" diet or so i thought. see below:

this histamine thing is very tricky. in my diligence to sub in low histamine items, i actually introduced some problematic things These bottled juices like unfiltered apple ( dr. peat did not recommend pulp due to mold risk- maybe that?),cranberry, blueberry - is it mold or histamine ? having reactions to them and my intestine has not been nearly as good since this diet change - i suspect due to whatever is in these juices to which i am allergic and also the young cheeses are not necessarily made traditionally with rennet so i dont know if im getting objectionable enzymes now? i now have to go back to Whole foods and walmart and return all these juices ( the concord grape i think may be ok and Dr. P recommended but its still in a bottle off of a shelf so?) and some of the cheese i think.

it just seems our world is completely histamine contaminated, even the apparently available" low histamine" choices due to the way they are processed and commercialized. and many of the supposedly low histamine foods are susceptible to mold. hard to know what is left to eat that is readily available in stores. must research on line and local farm sources and try to eat all fresh if possible.

My intestine has taken a dreadful turn for the worse the last week- very different from when i was drinking OJ and eating parmesan- and im still reacting to the impurities of the foods and juices despite their characterization as "low histamine", I suspect due to these other aspects I have enumerated above. I might be a little less congested not much; but seems the problematic aspects of the impurities in these items are canceling out any real progress for me thus far.

After 30 years of trial and error, i really think for me the answer is some real practitioner support and data. i found a place but its very expensive. but without knowing the underlying mechanisms, its all trial and error and ive been doing this way too long despite fixing all of my endocrinological issues., just got bloodwork back on all of that and it was impeccable- i look like the perfect female hormone and thyroid poster child based upon that with a hormone profile of a woman 30 years younger. Yet i am allergic to the planet earth. Go figure. All input welcome!-

But i continue to persist in resolving this final but insidious issue!

Its normal to have some digestive distress when the diet suddenly changes drastically. So this is a major factor that contributes to how this goes. And yes there are other things in juices and fruits that may cause symptoms. This is one of the reasons I could never stick to a heavy liquid diet.

 

[Advocate2021]

Its normal to have some digestive distress when the diet suddenly changes drastically. So this is a major factor that contributes to how this goes. And yes there are other things in juices and fruits that may cause symptoms. This is one of the reasons I could never stick to a heavy liquid diet.

after many healing measure, my intestine was doing pretty good so i take this as a clue that this diet at least in the form ive been doing it aint working- i think its the adulteration of the foods and not the foods themselves. so im resetting with coffee enemas and returning the juices and suspect cheeses and will start once again with a different version while i see if i can get some real data like testing.

 

[Advocate2021]

Reposting this here as its on the subject of my conversation here:

and please here all learn from my suffering this last week. Do not sacrifice purity for the sake of eliminating high histamine otherwise healthy foods like OJ and traditional cheese. i felt 100 times better on that than i do now on a week of other bottled juices from fruits on the approved lists and young cheeses made with God knows what type of enzymes. several coffee enema buckets later and just drinking some sugared milk with collagen and i feel 75 percent better already- will be back to baseline hopefully tomorrow and re-evaluate all this. still will try to go lower histamine but will start over with different foods- no bottled juices and no cheeses not made with real animal rennet for sure. i dont know if this is my issue or not frankly but i am all for trying but just sharing what i am learning so others might benefit. off to the gym after a day of challenge and trying to re-set from a week of chaos. oh also i am very allergic to nettle- found that out the hard way this week too- was like a bomb to me. if you have grass, weed, tree allergies be very careful with any herbal. things like tea tree, eucalyptus, chamomile, peppermint that many swear by for their sinuses absolutely kill me and for those with those allergies BEWARE. just because its natural doesnt mean its always good for everyone.

 

[Advocate2021]

Update and Repost: So, ive been on the low histamine diet now for about a month now- think ive gotten the hang of it. i do think it has had an effect on my general allergic threshhold as i have had some improvement in general congestion symptoms. But no effect whatsoever on the chemical sensitivities so I still feel i will need to dive in more scientifically to that. interestingly i ran into a rather eccentric woman on the juice isle at whole foods last night and ended up in an hour long conversation, inclusive of chemical sensitivity mechanisms- she was like a medical encyclopedia and there is a doctor here that deals with this and does all the testing for the various mechanisms she speaks of . We are both Jewish and she said these traits are prevalent in the Jewish line. So, wow- could be divine order. my endocrine system is great- all my hormone and blood work came back pristine. makes sense that i mastered this philosophy and attained great results but that this other issue is independent of that and that is why Dr. Peat could never nail it with me. So excited to hopefully get to the bottom of it.

 

[Hugh Johnson]

Sup everyone,

As many of you already know, I am the guy (Amongst many others) who got "cured" by cyproheptadine usage.

But what "cure" am I referring to???

Well, specifically, POST-SSRI-Sexual Dysfunction symptoms (PSSD).

I contracted PSSD from Ashwagandha usage, amongst many other dudes unfortunately.

You can read my viral article here:
https://medium.com/@LucasAoun/ashwagandha-can-cause-anhedonia-pssd-blunted-emotions-and-apathy-97fb99855f28


Now, what I need help with is developing THEORIES, as to WHY CYPRO WORKS.

But it doesn't work when we dose it acutely.

In fact, a single dose of cyproheptadine (<1mg), will cause the following effects:
-Horrible libido.
-Fatigue.
-Ravenous appetite.
-Incredible digestion.
-Numbing of all my emotions.


BUT...... It's the REBOUND of cypro.... That CURES us of PSSD.

DAY 4 and 5 AFTER using 1mg of cypro, there's this incredible SNAPBACK effect....

Orgasm returns, no more blunted libido, everything amazing.


But WHY....

What is happening 4 days after Cypro?

I need help understanding how to replicate these effects.

My current theories are as follows:
1. Cortisol rebound (So how to test?)
2. 5-HT1A receptor modulation (So how to test?)
3. Histamine rebound?


Can anyone please try and explain what is going on here?

Thanks all, love you lots!

I would assume it's just lower stress. Increase in stress feels good short term, while being destructive long term. The opposite is also true.


You were probably just stuck in a high stress state.

 

[metamorph]

I experienced this, I’ve come to think that it might be interesting to take a low dose 0.5mg long term. I’m always using it in specific periods, but I’ve also seen some research which showed great benefits after long term antihistamine use (6+ months) And Ray often speaks of 0.5mg or 1mg at most.

Any links to the research on benefits of long term antihistamine usage? Thanks

 

[AVTISTICVS]

@Lokzo @Tidal

This is what the cyproheptadine rebound is. I have had conversations with other people and the rebound has been observed in

Cypro
Amitriptyline
Mirtazapine
Mianserin

The reason the mechanism has eluded us is because the first two are old and the pharmacology records are outdated. Cypro came out in 1961. Like most drugs, it’s a center of attention then studies die off as new drugs come down the pipeline. It wasn’t until 1989 that inverse agonists were discovered. Cypro (and these other drugs) are all 5HT2C inverse agonists and 5HT2A antagonists. Inverse agonism causes a rebound super sensitization at the 5HT2 family. The reason 5HT2A antagonism is also needed is because of the push and pull relationship these two receptors have. They have multiple overlapping signaling cascades and opposing actions when it comes to serotonergic mediated dopamine modulation in select brain areas. I’ve also experienced the rebound the week after using MDMA (please don’t do this). MDMA heavily downregulates 5HT2A but not 5HT2C. I have also had windows on acute Clomipramime usage.

I’ve looked for options. Possibly a tiny dose of mirtazapine or mianserin a couple times per week could create an additive effect that could be sustained. Personally I will be trying low dose Abilify as it seems to be on the money pharmacology wise for the most part.

 

[Tidal]

@Lokzo @Tidal

This is what the cyproheptadine rebound is. I have had conversations with other people and the rebound has been observed in

Cypro
Amitriptyline
Mirtazapine
Mianserin

The reason the mechanism has eluded us is because the first two are old and the pharmacology records are outdated. Cypro came out in 1961. Like most drugs, it’s a center of attention then studies die off as new drugs come down the pipeline. It wasn’t until 1989 that inverse agonists were discovered. Cypro (and these other drugs) are all 5HT2C inverse agonists and 5HT2A antagonists. Inverse agonism causes a rebound super sensitization at the 5HT2 family. The reason 5HT2A antagonism is also needed is because of the push and pull relationship these two receptors have. They have multiple overlapping signaling cascades and opposing actions when it comes to serotonergic mediated dopamine modulation in select brain areas. I’ve also experienced the rebound the week after using MDMA (please don’t do this). MDMA heavily downregulates 5HT2A but not 5HT2C. I have also had windows on acute Clomipramime usage.

I’ve looked for options. Possibly a tiny dose of mirtazapine or mianserin a couple times per week could create an additive effect that could be sustained. Personally I will be trying low dose Abilify as it seems to be on the money pharmacology wise for the most part.

Are you saying that stopping an inverse agonist causes temporary 5ht2c sensitization?

So I guess that taking amitriptyline at high dose can desensitize 5ht2c receptors?
And could that cause depersonalization and emotional blunting.

I know 5ht2c is linked to food intake and I am literally hungry all the time though not quite as bad as when taking it.

I don't know about 5ht2a. All I know is Myo inositol is supposed to sensitise this but was the worst supplement I could ever take given the effects it had.

 

[AVTISTICVS]

Are you saying that stopping an inverse agonist causes temporary 5ht2c sensitization?

So I guess that taking amitriptyline at high dose can desensitize 5ht2c receptors?
And could that cause depersonalization and emotional blunting.

I know 5ht2c is linked to food intake and I am literally hungry all the time though not quite as bad as when taking it.

I don't know about 5ht2a. All I know is Myo inositol is supposed to sensitise this but was the worst supplement I could ever take given the effects it had.

Generally speaking, yes 5HT2C inverse agonists cause super-sensitization because of the constitutive suppression.

Amitriptyline is an inverse agonist. As such is causes sensitization.

It is suppression of 5HT2C that increases appetite. Increased activity (by itself) suppresses appetite. See Lorcaserin.

Inositol does much more than just downregulate 5HT2A.