Awful Response To Cyproheptadine

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Anonymous

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I don't respond well to this med. I don't get it. It's described as a "wonder drug" but when I take I feel awful. Angry/irritable, cold hands and feet, etc.

Ugh!!!!!!!! So annoyed I thought it would help my situation
 

narouz

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JRMoney15 said:
I don't respond well to this med. I don't get it. It's described as a "wonder drug" but when I take I feel awful. Angry/irritable, cold hands and feet, etc.

Ugh!!!!!!!! So annoyed I thought it would help my situation

Yeah, sorry.
We could probably create an interesting research niche
by exploring why different people respond so differently to these Peat-related pharmas! :)

I tried Lisuride after hearing how some here on the forum
felt amazing and semi-euphoric while taking it.
I felt very lethargic and almost had to go lie down. :lol:

There's probably a very interesting explanation behind the different reactions.
Could provide some clues to our chemistries, issues....
 

BobbyDukes

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Cypro is a anti-histamine. It's going to make you feel like crap because of the somnolence. Its also a 5ht2a antagonist, which is a anti-psychotic mechanism. I've never understood why people here expect a marked mood enhancing effect from it. If something makes you feel REALLY good, there's a good chance you'll crash and burn further down the road. That's homeostasis.

Peat talks about cypro reducing stress, and it does that. But it's never going to make you feel like a million bucks (unless you tolerate it's hard hitting somnolence). The SSRIs, for a lot of people, are actually far more potent mood enhancers (but then, serotonin is excitatory), especially during the adaption period.

Lusuride is different, because its a dopamine agonist. It actually increases dopamine (unlike cypro). So this will antagonize serotonin and prolactin. But, dopamine agonists are also notorious for also causing solomnemce. They all have an adaption period that many cannot tolerate. It can take weeks to hit a plateau with the drug, and even then, who wants to be hooked/reliant upon a dopamine agonist? That won't be fun coming off've it. I'm pretty sure Peat doesn't recommend drugs at all, unless they are absolutely needed.

Cypro has pretty profoundly negative effects for me, too. Awful mood, anhedonia, no libido at all, irritable and can't wait for the drug to be out of my body. Not even coffee can lift me from such a miserable state. It certainly works for sleep though. Reduces restless legs a treat.
 

Dean

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I'm really back and forth and all around about whether to try it. Some respond well, others not. Some say it is burdensome to the liver, others say it burdens the liver less than any other anti-histamine. I was thinking of trying it as a replacement for my usual daily OTC anti-histamine with hopes it might also help with my recurring sinus headaches and do its anti-serotonin routine to boot. BUT, Peat says not to take it long term...so, it doesn't seem to fit the bill as a replacement for my daily anti-histamine.

Maybe ondansetron is the better option? It doesn't antagonize dopamine. I think I read somewhere in another thread about taking ondansetron in the morning and cyproheptadine at night (can't find it now). What about that? What about doing the cabergoline thing twice a week with the cypro, to offset the somnolence?
 

jyb

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Dean said:
I'm really back and forth and all around about whether to try it. Some respond well, others not. Some say it is burdensome to the liver, others say it burdens the liver less than any other anti-histamine. I was thinking of trying it as a replacement for my usual daily OTC anti-histamine with hopes it might also help with my recurring sinus headaches and do its anti-serotonin routine to boot. BUT, Peat says not to take it long term...so, it doesn't seem to fit the bill as a replacement for my daily anti-histamine.

Maybe ondansetron is the better option? It doesn't antagonize dopamine. I think I read somewhere in another thread about taking ondansetron in the morning and cyproheptadine at night (can't find it now). What about that? What about doing the cabergoline thing twice a week with the cypro, to offset the somnolence?

He advises not to take it long term just like any drug. It's not specific to cypro. But if you have to take an anti-histamine, cypro is supposedly one of the safest. It is not meant to be more burdensome to the liver than other drugs.

Taken long term some anti-serotonin drugs have been suspected to cause side effects on the heart. I think haidut agrees cypro is not one of them. How about your medication? cypro is an old drug and has been studied for decades...
 

jyb

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JRMoney15 said:
I don't respond well to this med. I don't get it. It's described as a "wonder drug" but when I take I feel awful. Angry/irritable, cold hands and feet, etc.

Ugh!!!!!!!! So annoyed I thought it would help my situation

It's a possibility that most if not all drugs you'll experiment with will end up like that for you. Read the testimonials on this forum and you'll get the idea. But drugs are not necessarily more powerful nor useful than just suitably chosen food.
 

haidut

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jyb said:
Dean said:
I'm really back and forth and all around about whether to try it. Some respond well, others not. Some say it is burdensome to the liver, others say it burdens the liver less than any other anti-histamine. I was thinking of trying it as a replacement for my usual daily OTC anti-histamine with hopes it might also help with my recurring sinus headaches and do its anti-serotonin routine to boot. BUT, Peat says not to take it long term...so, it doesn't seem to fit the bill as a replacement for my daily anti-histamine.

Maybe ondansetron is the better option? It doesn't antagonize dopamine. I think I read somewhere in another thread about taking ondansetron in the morning and cyproheptadine at night (can't find it now). What about that? What about doing the cabergoline thing twice a week with the cypro, to offset the somnolence?

He advises not to take it long term just like any drug. It's not specific to cypro. But if you have to take an anti-histamine, cypro is supposedly one of the safest. It is not meant to be more burdensome to the liver than other drugs.

Taken long term some anti-serotonin drugs have been suspected to cause side effects on the heart. I think haidut agrees cypro is not one of them. How about your medication? cypro is an old drug and has been studied for decades...

Of all the serotonin antagonists cyproheptadine is the safest. Ondansetron (and all other -setrons) are known to prolong the QT interval and potentially lead to a lethal heart arhytmia. The incidence of these cases is not well researched. Of all the dopaminergic drugs, lisuride is probably the safest. You can get a similar effect to lisuride by combining cabergoline and cyproheptadine. Cabergoline on its own has some pretty nasty side effects causing fibrosis of the heart and lungs. Combining lisuride and cyprois also fine and probably even safer than the cabergoline cypro combo. Newer dopaminergic drugs like pramipexole have not been studied enough, even though they seem OK for now. I agree with Peat's principle to not trust drugs that have not been in the market for at least 20 years. Clinical trials are nothing more than a sharade proving merely that a drug won't kill too many people in too short of a time.
Back to cyproheptadine. If you take cypro for 2-3 days the sedating effects disappear and after that you should be able to see why I think it's the best drug in Peat world after aspirin. Keep in mind that Peat said blocking histamine blocks all of estrogen's effects. So, cyproheptadine does all of the following:

- blocks serotonin
- blocks estrogen effects (through histamine)
- blocks histamine (the most powerful anti-histamine in use)
- lowers prolactin
- lowers human growth hormone
- blocks cholinergic activity
- blocks muscarinic "receptors"
- lowers prostaglandin production (so is anti-aromatase like aspirin)
- lowers cortisol (especially at night)
- lowers adrenalin (especially at night)
- increases GABA release in the brain
- antagonizes glutamate (the main mechanism behind the most effective anti-depressant drugs)
- lowers endorphins
- has strong anesthetic properties
- has calcium channel blocking properties (treats heart disease and migraines, protects against EMR)
- lowers aldosterone (spares magnesium)

I challenge anybody to find another drug that has even half as many Peat-friendly qualities, which of course translates into cyproheptadine being very effective for a number of serious conditions. Let's pick cancer as an example of such serious conditions. Peat wrote an article about promising approaches to cancer treatments.
http://raypeat.com/articles/articles/ca ... rone.shtml

In that article he wrote:
"...There are several types of drug---carbonic anhydrase inhibitors, to increase carbon dioxide in the tissues, lysergic acid derivatives, to block serotonin and suppress prolactin, anti-opiates, antiexcitotoxic and GABAergic agents, anesthetics, antihistamines, anticholinergics, salicylic acid derivatives---that could probably be useful in a comprehensive therapy for cancer, but their combinations won't be explored as long as treatments are designed only to kill."

As you can see cyproheptadine covers most of these requirements. In fact, I would love to do a rodent study with acetazolamide, cyproheptadine, and aspirin (separate and as a combo) as a comprehensive treatment for cancer. I bet cypro alone and especially in combination with aspirin would be very effective.

Just consider these two studies:
http://www.ncbi.nlm.nih.gov/pubmed/11459201 (colon cancer rodent model)
"...While DMXAA alone (20 mg/kg) showed little or no antitumour activity, coadministration with cyproheptadine was curative in four of five mice."

http://www.ncbi.nlm.nih.gov/pubmed/23076705
"...We reported two cases of hepatocellular carcinoma (HCC) with lung metastases who were treated with a combination of thalidomide and cyproheptadine. The use of cyproheptadine in these two cases was originally for skin itching. Follow-up CT images revealed a complete remission of HCC in both of them after treatment for 6 months and 6 weeks, respectively. A following experimental cell line study demonstrated that cyproheptadine effectively reduced the viability of two HCC cell lines."

Does anybody know of a drug that has demonstrated such strong anti-cancer activity in advanced cancers (with metastases), to the point that the mouse study called the cyproheptadine effect curative? If you do, please share it since it probably has many of cypro's qualities and deserves to be reviewed and studies.

If you consider cancer as the extreme derangement of metabolism, there are a number of less serious conditions along the metabolic spectrum that should be treatable by cyproheptadine (maybe in combination with aspirin for a highly additive effect). These conditions include diabetes, heart disease, MS, ALS, Chron's / IBD, COPD, all kinds of fibrosis, etc.
Just the fact that cyproheptadine alone addresses the 3 cardinal metabolic poisons in Peat world (prolactin, serotonin, estrogen) should make it part of the arsenal of every Peatarian struggling to restore proper metabolic health with diet alone.
Just my 2c.
 

moss

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Thanks Haidut
I know someone who was on Bromocriptine had unpleasant side effects, now on Cabergoline so this is very helpful indeed.
 

haidut

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moss said:
Thanks Haidut
I know someone who was on Bromocriptine had unpleasant side effects, now on Cabergoline so this is very helpful indeed.

Actually bromocriptine is safer than cabergoline, but the psychological side effects are perceived as more unpleasant than cabergoline's. Low dose cabergoline (0.25mg-0.5mg twice a week) are probably safe and in most people have been shown to not cause the dreaded heart valve fibrosis, but there have been isolated cases where even the low dose causes these side effects. The reason for the side effects is that cabergline and some other related dopaminergic drugs like pergolide are actually mixed dopamine-serotonin agonists, and their agonism of the 5-HT2B receptor is what causes the fibrosis. Lisuride is notable among those drugs that it does not agonize 5-HT2B but rather antagonizes it. However, lisuride is also mixed dopamine-serotonin agonist and is agonist of the 5-HT1A receptor. If you want dopamine agonism combined with serotonin antagonism you have 2 choice. Either take one of the newer (and untested) drugs like pramipexome, which are pure dopaminergic agonists or combine one of the older and well-known dopaminergic-serotonergic drugs with a general serotonin antagonist like cyproheptadine. Cypro has been shown to protect from the dreaded side effects of cabergoline and its related drugs. Here are some studies showing lisuride is safe and cypro protects from fibrosis caused through 5-HT2B.

http://www.ncbi.nlm.nih.gov/pubmed/16614540 (lisuride)
http://www.ncbi.nlm.nih.gov/pubmed/19346455 (cypro)

Also here are more more studies explaining the side effects of drugs like cabergoline, pergolide, metergoline, methysergide (all of which have known side effects of fibrosis of heart / lungs).
http://www.ncbi.nlm.nih.gov/pubmed/25076559
http://www.ncbi.nlm.nih.gov/pubmed/20671305
 

Dean

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Thank you, Haidut. So, I guess you would agree with the post above that if I am already taking an anti-histamine, it would be kind of ridiculous for me to not switch to cyproheptadine. In the last few months, I doubled my otc anti-histamine dose to 50 mg, after years at 25 mg, due to an increasing lack of effectiveness. I've been taking it all at night to also help with sleep. Cyproheptadine would seem to be a lot stronger than the other anti-histamines since people here are reporting major somnolence at such small doses. I took 25 mg of otc anti-histamines every morning for years and didn't have noticeable issues. I guess it is the serotonin antagonism that makes cypro especially somnolent?

What non-pharma route could you go to offset cypro's negatives? I'm kind of sensitive to caffeine, but perhaps the caffeine/theanine combo you've talked about could be helpful?
 

Peata

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For me, cyproheptadine has been great, where I had terrible results with another of the peat-favored substances - pregnenolone.

I take 2mg cypro over the day to total 8 mg. I worked up to that slowly. It does make you feel zombified at first, but I found tolerance develops quickly and I stopped having any of that zonked-out feeling long ago.

Surprisingly, it doesn't seem to work for my allergy symptoms like Benadryl does.

I don't know what all it does, but the one thing I'm sure of is that it helps my mood. Not in a drugged feeling, but in a more subtle way that let's me feel like me, only the best me. No negative effect on libido, no flatline of emotions as with SSRI's. My mood is fine, outlook on life is good, less worry and fear, etc. As long as my blood sugar is kept up -That's always the first thing I check when I feel a negative change in mood - I probably need to eat something.
 

Dean

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Peata, that sounds promising. Strange though that it doesn't seem to help you as an anti-histamine. As for the zonked out feeling, I had that at first when I doubled my anti-histamine dose. Even taking it at night, I would wake up feeling very groggy for the first little while; but it hasn't been as much an issue since the initial period.
 

moss

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haidut said:
moss said:
Thanks Haidut
I know someone who was on Bromocriptine had unpleasant side effects, now on Cabergoline so this is very helpful indeed.

Actually bromocriptine is safer than cabergoline, but the psychological side effects are perceived as more unpleasant than cabergoline's. Low dose cabergoline (0.25mg-0.5mg twice a week) are probably safe and in most people have been shown to not cause the dreaded heart valve fibrosis, but there have been isolated cases where even the low dose causes these side effects. The reason for the side effects is that cabergline and some other related dopaminergic drugs like pergolide are actually mixed dopamine-serotonin agonists, and their agonism of the 5-HT2B receptor is what causes the fibrosis. Lisuride is notable among those drugs that it does not agonize 5-HT2B but rather antagonizes it. However, lisuride is also mixed dopamine-serotonin agonist and is agonist of the 5-HT1A receptor. If you want dopamine agonism combined with serotonin antagonism you have 2 choice. Either take one of the newer (and untested) drugs like pramipexome, which are pure dopaminergic agonists or combine one of the older and well-known dopaminergic-serotonergic drugs with a general serotonin antagonist like cyproheptadine. Cypro has been shown to protect from the dreaded side effects of cabergoline and its related drugs. Here are some studies showing lisuride is safe and cypro protects from fibrosis caused through 5-HT2B.

http://www.ncbi.nlm.nih.gov/pubmed/16614540 (lisuride)
http://www.ncbi.nlm.nih.gov/pubmed/19346455 (cypro)

Also here are more more studies explaining the side effects of drugs like cabergoline, pergolide, metergoline, methysergide (all of which have known side effects of fibrosis of heart / lungs).
http://www.ncbi.nlm.nih.gov/pubmed/25076559
http://www.ncbi.nlm.nih.gov/pubmed/20671305

Yes I agree, bromocriptine is safer. Person in mind is on the lowest lose dose of cabergoline and has regular heart checks. I will share this information with her so she can do some research before her next scheduled appt with her endo. Obviously for PD pts who are on much higher doses it would be of particular concern. I appreciate your very thoughtful response. Thanks.
 

haidut

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Dean said:
Thank you, Haidut. So, I guess you would agree with the post above that if I am already taking an anti-histamine, it would be kind of ridiculous for me to not switch to cyproheptadine. In the last few months, I doubled my otc anti-histamine dose to 50 mg, after years at 25 mg, due to an increasing lack of effectiveness. I've been taking it all at night to also help with sleep. Cyproheptadine would seem to be a lot stronger than the other anti-histamines since people here are reporting major somnolence at such small doses. I took 25 mg of otc anti-histamines every morning for years and didn't have noticeable issues. I guess it is the serotonin antagonism that makes cypro especially somnolent?

What non-pharma route could you go to offset cypro's negatives? I'm kind of sensitive to caffeine, but perhaps the caffeine/theanine combo you've talked about could be helpful?

Yeah, I think that if you are going to use an antihistamine there is no reason to not try cypro first. Btw, some people over at Peatarian.com have been talking about taking ketotifen, which is structurally very similar to cypro. However, I did not like the feeling of ketotifen and I found out it increases NO by stimulating NOS. Here is one study showing that effect of ketotifen:
http://www.ncbi.nlm.nih.gov/pubmed/9113377

As far as combating the somnolence of cypro, if you can't handle higher doses of caffeine you can try nicotine gum. It does have stimulating effect on the brain. As per Peat's recommendations I would keep nicotine dosage low (<=4mg daily) since it is cholinergic and can also stimulate glycolysis. Also, make sure you chew it after ingesting some sugar since it may trigger an adrenalin response if you are underfed. The cypro should negate some of the adrenalin effects of nicotine but eat the sugar just in case.
 

narouz

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One of the weird things about cyproheptadine
is that, for me,
it had no noticeable anti-histamine effect.
I think someone else mentioned that upthread or on a related thread.

On the sleepiness issue:
It surely does have that!
But I wonder how much people are taking.
At first it kicked my butt even in small doses;
I slept from like midnight 'til noon.
But keeping to 1 or 2mgs at bedtime for about a week
I did find the zombification-the-next-day to diminish to being unnoticeable.
 

Peata

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narouz said:
One of the weird things about cyproheptadine
is that, for me,
it had no noticeable anti-histamine effect.
I think someone else mentioned that upthread or on a related thread.

Yes, I have the same lack of anti-histamine effect.
 

jyb

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narouz said:
One of the weird things about cyproheptadine
is that, for me,
it had no noticeable anti-histamine effect.
I think someone else mentioned that upthread or on a related thread.

How do you know you're expecting histamine reaction? Unless you have a known allergy...
 

narouz

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jyb said:
narouz said:
One of the weird things about cyproheptadine
is that, for me,
it had no noticeable anti-histamine effect.
I think someone else mentioned that upthread or on a related thread.

How do you know you're expecting histamine reaction? Unless you have a known allergy...

Yeah, I guess I should've explained:
During that time I started taking cypro
I was being plagued by a very very itchy corner of my right eye (and sometimes left eye too a bit).
Also, some congestion upon arising.
Usually Benadryl had a strong impact on those things.

Maybe those symptoms are something other than allergy.

Or maybe cypro at such low doses, 1-3mg per day,
isn't effective as an antihistamine.
But sheesh! That would be a daunting challenge for me,
to take huge doses of cyproheptadine.
Maybe many did back then when it came out.
 

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