Cyproheptadine & Bodybuilding - ZERO Pumps?

[haidut]

@haidut You mentioned that doses up to 2mg will tend to lower prolactin, but that doses > 2 or 4mg can raise prolactin due to dopamine antagonism. Many people have repeated this claim in several threads, but so far I have never seen any study demonstrating that, and as far as I can see you haven't cited anything, either. Do you know of any study/trial where they actually reported raised prolactin?



The studies in the thread you linked to show prolactin levels in response to TRH injection. Basal levels were lowered by cyproheptadine, and in hyperprolactinemia even very large doses of cypro lower prolactin very drastically. Even metergoline does not prevent a prolactine increase after TRH stimulation.

J Reprod Med. 1987 Feb;32(2):115-9.
Metergoline as an inhibitor of prolactin release.
Caballero A Sr, Mena P, Caballero-Díaz JL, Caballero-Asensi A.
Abstract
In a randomized, double-blind study, 12 and 16 mg of metergoline and 5 mg of bromoergocriptine were given daily to three groups of 100 women each for ten consecutive days to prevent lactation. Excellent or good results were obtained in 86%, 90% and 83%, respectively. Serum prolactin (PRL) levels were evaluated in three settings. The first was after a single dose in four groups of patients (4, 6 and 8 mg of metergoline and 2.5 mg of bromoergocriptine were studied for ten hours). Second, for a study of the suckling reflex, PRL levels were measured 15, 30 and 60 minutes after breast stimulation in four groups of five patients each: two groups on the fourth postpartum day with and without metergoline treatment and two groups on the eighth postpartum day (the reflex was suppressed in the two groups treated with metergoline). Third, serum PRL levels rose after the intravenous administration of 200 mg of thyrotropin-releasing hormone (TRH) in another two groups of ten patients, one treated with metergoline and the other not so treated. TRH stimulation was not blocked in the treated groups.

Here is one. Yes, the animals had prolactinoma but it is an in vivo study and other dopaminergic chemicals like bromoriptine reliably lower PRL in humans or animals with such condition.
Effects of Cyproheptadine on Prolactin Synthesis and Release by Normal and Suppressed Pituitary Glands and by Dispersed Pituitary Tumor Cells *
"..Chronic administration of cyproheptadine to rats bearing a transplantable PRL-secreting pituitary tumor, however, had a stimulating effect on the PRL synthesis and release by the suppressed, atrophied pituitary glands of these animals. In addition, methysergide administration also increased the radioimmunoassayable PRL content of the pituitary gland and additionally stimulated the growth of atrophied pituitary gland in tumor-bearing rats."

In addition, cypro enhanced the TRH-stimulated prolactin release. This is different than simply not being able to block it and as you cans even the authors of that study refer to cypro's anti-dopaminergic effects as an explanation.
Augmentation of prolactin response to TRH after cyproheptadine
"...Serum PRL, TSH, T3 and T4 were estimated in the basal state and following iv bolus injection of 100 μg synthetic thyrotropin releasing hormone before and 7 days after cyproheptadine treatment in 5 healthy adult males. Only the PRL response to TRH was augmented after cyproheptadine. This is perhaps related to the antidopaminergic effect of cyproheptadine."

Given that cyproheptadine's dopamine blocking effects have been confirmed and the affinity for D receptors is more or less known, I'd use the minimum dose that blocks serotonin receptors but does not affect the dopamine ones. I think this is also a reason Peat never recommends more than 4mg cypro daily and usually caps it at 2mg even for people with cancer.

 

[Kartoffel]

Here is one. Yes, the animals had prolactinoma but it is an in vivo study and other dopaminergic chemicals like bromoriptine reliably lower PRL in humans or animals with such condition.
Effects of Cyproheptadine on Prolactin Synthesis and Release by Normal and Suppressed Pituitary Glands and by Dispersed Pituitary Tumor Cells *
"..Chronic administration of cyproheptadine to rats bearing a transplantable PRL-secreting pituitary tumor, however, had a stimulating effect on the PRL synthesis and release by the suppressed, atrophied pituitary glands of these animals. In addition, methysergide administration also increased the radioimmunoassayable PRL content of the pituitary gland and additionally stimulated the growth of atrophied pituitary gland in tumor-bearing rats."

In addition, cypro enhanced the TRH-stimulated prolactin release. This is different than simply not being able to block it and as you cans even the authors of that study refer to cypro's anti-dopaminergic effects as an explanation.
Augmentation of prolactin response to TRH after cyproheptadine
"...Serum PRL, TSH, T3 and T4 were estimated in the basal state and following iv bolus injection of 100 μg synthetic thyrotropin releasing hormone before and 7 days after cyproheptadine treatment in 5 healthy adult males. Only the PRL response to TRH was augmented after cyproheptadine. This is perhaps related to the antidopaminergic effect of cyproheptadine."

Thanks for your reply. I briefly went throught the first study you posted. Maybe I'm missing sth but it looks like serum prolactin was not icreased in the rats with the transplanted tumors. Looking at figure 3, the cyproheptadine only increased synthesis by the pituitary, where the rate was still much lower than in healthy controls. So, this simply looks like some normalizing effect on the pituitary, rather than stimulation.
Concerning the second study, I already mentioned in another thread that the cyproheptadine did actually lower basal prolactin, and only amplified the response to TRH. I also posted a study showing that metergoline does the same thing, so this effect is not limited to cyproheptadine, and I doubt it is mediated by dopamine. The authors state that they suspect dopamine.

No significant change (p > 0.05) in basal serum prolactin (mean± SE) before (432 ± 60 mIU/L) and after (355.7 ± 24.3 mIU/L) 7 days of cyproheptadine therapy was noted. The TRH induced rise in PRL after cyproheptadine was significantly higher (p < 0.1) than that before cyproheptadine: rise before = 940 mIU/L and after cyproheptadine therapy = 1040 mIU/L (Fig. 1)

However, this mechanism cannot explain the augmented PRL response to TRH in cyproheptadine treated normal subjects. Cyproheptadine is not known to decrease the metabolie clearance of PRL stimulate any PRL releasing factor or to inhibit the PRL releasing inhibiting factor. However, cyproheptadine, in addition to being antiserotoninergic, is also known to have signilicant antidopaminergic and antihistaminic properties. Dopamine has been identified as the PRL inhibiting lactor
​

The thing that bothers me is that they don't provide any reference for that claim, and I guess I remain sceptical on the connection between cypro, dopamine, and prolactin. I think these studies are ground to be careful with larger doseses. However, the few papers mentioning this model of causation all use some external stimulation like TRH, and as I said, there are many papers in which cypropheptadine is used successfully to treat hyperprolactenemia, and no human trial using doses of 10mg+ ever reported an effect. If it were a significant dopamine antagonist, I think we would see different results.

Given that cyproheptadine's dopamine blocking effects have been confirmed and the affinity for D receptors is more or less known, I'd use the minimum dose that blocks serotonin receptors but does not affect the dopamine ones. I think this is also a reason Peat never recommends more than 4mg cypro daily and usually caps it at 2mg even for people with cancer.

Did he write that to you personally or where do these numbers come from? I recently asked him, if higher doses are safe, and he said yes. He said that too much can have a temporary, stupefying effect, and that lower doses will become more effective over time. Yet, he also said that he knew many people that took doses ranging from 10-30mg daily.

"I suggest that people start with a minimal dose to see how much is enough, because sensitivities vary greatly. I know people who were in bad shape for more than a day after one dose of 4 mg; I know a woman who needed 25 mg/day to feel right, but after a few weeks never needed it again. I found that the effect of one milligram increased after a few days, and with repeated use a tenth of a milligram was as effective as the first mg had been."
​

When I asked him whether 4-6mg are safe over months he said:

"Yes. I knew a woman who was having menstrual hemorrhages and fainting, who increased it to as much as 28 mg/day, After a few weeks she stopped taking it, and ten years later continues in good health."

"I think the stupefying effects an overdose has represents a general dulling, including the catecholamines and acetylcholine."

​

 

[Lokzo]

I think cypro definitely helps with strength and endurance as it blocks formation of lactic acid and prevents the so-called "central fatigue". It does cause sedation but once that effect wears off with chronic use all that remains is the ergogenic effects. Try it for a week or two and you will see.

Thanks Haidut,
I am really starting to love cypro. 1mg about 3 hours before bed, with ***t loads of carbs.
I feel amazing the next day provided I suppot my cortisol.

It somehow cures my PSSD when it wears off (3 days later) and seems to stack very well with ALCAR.
I just need to be careful it doesn't push my Thyroid too high , as I'm already borderline Hyper Thyroid

 

[haidut]

Thanks for your reply. I briefly went throught the first study you posted. Maybe I'm missing sth but it looks like serum prolactin was not icreased in the rats with the transplanted tumors. Looking at figure 3, the cyproheptadine only increased synthesis by the pituitary, where the rate was still much lower than in healthy controls. So, this simply looks like some normalizing effect on the pituitary, rather than stimulation.
Concerning the second study, I already mentioned in another thread that the cyproheptadine did actually lower basal prolactin, and only amplified the response to TRH. I also posted a study showing that metergoline does the same thing, so this effect is not limited to cyproheptadine, and I doubt it is mediated by dopamine. The authors state that they suspect dopamine.

No significant change (p > 0.05) in basal serum prolactin (mean± SE) before (432 ± 60 mIU/L) and after (355.7 ± 24.3 mIU/L) 7 days of cyproheptadine therapy was noted. The TRH induced rise in PRL after cyproheptadine was significantly higher (p < 0.1) than that before cyproheptadine: rise before = 940 mIU/L and after cyproheptadine therapy = 1040 mIU/L (Fig. 1)

However, this mechanism cannot explain the augmented PRL response to TRH in cyproheptadine treated normal subjects. Cyproheptadine is not known to decrease the metabolie clearance of PRL stimulate any PRL releasing factor or to inhibit the PRL releasing inhibiting factor. However, cyproheptadine, in addition to being antiserotoninergic, is also known to have signilicant antidopaminergic and antihistaminic properties. Dopamine has been identified as the PRL inhibiting lactor
​

The thing that bothers me is that they don't provide any reference for that claim, and I guess I remain sceptical on the connection between cypro, dopamine, and prolactin. I think these studies are ground to be careful with larger doseses. However, the few papers mentioning this model of causation all use some external stimulation like TRH, and as I said, there are many papers in which cypropheptadine is used successfully to treat hyperprolactenemia, and no human trial using doses of 10mg+ ever reported an effect. If it were a significant dopamine antagonist, I think we would see different results.



Did he write that to you personally or where do these numbers come from? I recently asked him, if higher doses are safe, and he said yes. He said that too much can have a temporary, stupefying effect, and that lower doses will become more effective over time. Yet, he also said that he knew many people that took doses ranging from 10-30mg daily.

"I suggest that people start with a minimal dose to see how much is enough, because sensitivities vary greatly. I know people who were in bad shape for more than a day after one dose of 4 mg; I know a woman who needed 25 mg/day to feel right, but after a few weeks never needed it again. I found that the effect of one milligram increased after a few days, and with repeated use a tenth of a milligram was as effective as the first mg had been."
​

When I asked him whether 4-6mg are safe over months he said:

"Yes. I knew a woman who was having menstrual hemorrhages and fainting, who increased it to as much as 28 mg/day, After a few weeks she stopped taking it, and ten years later continues in good health."

"I think the stupefying effects an overdose has represents a general dulling, including the catecholamines and acetylcholine."

​

There are other emails about this on the forum but yes, he did respond to me that lower doses are safer and he does not think more than 2mg daily should be used unless the person has a very serious issue like cancer or Alzheimer. My email to him was in regards to the liver enzyme elevation due to cypro and also potentially gallbladder issues. He concurred and said cypro can cause those issues in higher doses and due to its potential for also blocking dopamine receptors he thought lower doses and/or brief usage were key. He does seem to change his mind a lot on this issue but if lower doses over time achieve the same effects as higher doses then it I guess that would be the way to go if safety is key.

 

[Logan-]

There are other emails about this on the forum but yes, he did respond to me that lower doses are safer and he does not think more than 2mg daily should be used unless the person has a very serious issue like cancer or Alzheimer. My email to him was in regards to the liver enzyme elevation due to cypro and also potentially gallbladder issues. He concurred and said cypro can cause those issues in higher doses and due to its potential for also blocking dopamine receptors he thought lower doses and/or brief usage were key. He does seem to change his mind a lot on this issue but if lower doses over time achieve the same effects as higher doses then it I guess that would be the way to go if safety is key.

Did he specifically mention "dopamine blockage" as the reason for suggesting lower doses and/or brief usage in his email to you?

 

[haidut]

Did he specifically mention "dopamine blockage" as the reason for suggesting lower doses and/or brief usage in his email to you?

No, he specifically mentioned the liver/gallbladder issues. However, plenty of people have complained about the anti-dopamine effects of higher doses and when this is combined with the known cypro affinity for dopamine receptors that is enough evidence for me. Read through the Wikipedia page on cypro. It shows affinity for various receptors.

 

[Lokzo]

Try some pregnenolone, that always gives me a nice pump. Throwing in some high quality vitamin E if you got it, about 100-200ius daily, will combine with the preg real nicely to promote androgen production while inhibiting estrogens at the same time.

I am interested in experimenting with Pregnenolone - hoping it can raise cortisol. Also, do you worry about down-regulation? Or is this prohormone somewhat safer longer term?

 

[Lokzo]

As above, 4mg is a huge dose. Try much lower.

Every day I seem to see you posting about a new supplement. Maybe you’re taking too many (and too much of each), and/or mixing them up too much.

You are spot on. I do experiment with too many things I admit. It's something I am cutting back on. You're not the first person to tell me this.

 

[TeaRex14]

I am interested in experimenting with Pregnenolone - hoping it can raise cortisol. Also, do you worry about down-regulation? Or is this prohormone somewhat safer longer term?

I think pregnenolone can raise cortisol when you're actually low in cortisol, because it's a prehomrone and one of the conversion pathways is into cortisol. However taking preg in combination with other things, such as aspirin, might prevent this. I don't know where the thread is at exactly, but there's been a discussion on down regulation of endogenous hormones from preg supplementation and they concluded that it doesn't have much of an effect. Can actually encourage an increased production in endogenous hormones in some cases.

 

[Momado965]

I was literally losing weight on Cyproheptadine - even though I was eating upwards of 700 grams of carbs per day! It definitely reduced water retention, probably because it was altering my already VERY low aldosterone and cortisol.
But somehow it is a cure for my PSSD when it wears off - 4 days after using it - it completely feels like it fixes my PSSD.

Told ya its an awesome drug.

 

[Lokzo]

I think pregnenolone can raise cortisol when you're actually low in cortisol, because it's a prehomrone and one of the conversion pathways is into cortisol. However taking preg in combination with other things, such as aspirin, might prevent this. I don't know where the thread is at exactly, but there's been a discussion on down regulation of endogenous hormones from preg supplementation and they concluded that it doesn't have much of an effect. Can actually encourage an increased production in endogenous hormones in some cases.

Ahhh okay I see. Thanks for that. I will give it a try in a few months down the track. Right now I have faith in Cypro. I was feeling amazing for 10 days after dosing cypro, and then I ate some cooled potatoes, and that has made me feel like crap!!! I know there are other guys on this forum that complain of starch making them feel less androgenic.

 

[Lokzo]

Told ya its an awesome drug.

I love it. I love it when it *wears off*

It definitely is going to be a long term keeper. I plan on using it less and less over time.

 

[Momado965]

I love it. I love it when it *wears off*

It definitely is going to be a long term keeper. I plan on using it less and less over time.

Im at 3mg a day. Takes of any endotoxin feeling I get from starch. Rices ***** up my gut real quick. Wheat and potatoes potatoes do not.

 

[Lokzo]

Im at 3mg a day. Takes of any endotoxin feeling I get from starch. Rices ***** up my gut real quick. Wheat and potatoes potatoes do not.

I agree cypro is amazing for endotoxin reduction. Interesting RE rice starch!

Also - at that dosage, you have strong libido?

 

[mujuro]

I’m guessing weakness is due to neuronal K+ efflux from H1 antagonism, meaning a higher threshold required for action potential. When I take an antihistamine, everything feels more difficult, physical and mental. Why not take it before bed? It suppresses the morning cortisol elevations.

 

[Lokzo]

I’m guessing weakness is due to neuronal K+ efflux from H1 antagonism, meaning a higher threshold required for action potential. When I take an antihistamine, everything feels more difficult, physical and mental. Why not take it before bed? It suppresses the morning cortisol elevations.

I like that theory. I do take it 4 hours before bed. Works like a charm for sleep. But, the weakness is still definitely noticeable the next day.

One of the questions I've been pondering is why doesn't cypro induce a potent sedating effect for me? Like I remember the first few times I tried it, I thought it was going to hit me very hard, but in fact, it was easily manageable and I barely noticed any drowsiness.

 

[brix]

It makes me so depressed when I take it. Hard to work out or even function the next day or two. I do like it for sleep and chilling out but even at.5mg the effects are strong.

 

[Lokzo]

It makes me so depressed when I take it. Hard to work out or even function the next day or two. I do like it for sleep and chilling out but even at.5mg the effects are strong.

It does feel emotionally blunting during use I agree, and working out is SUCH a struggle. I had about 1.5mg last night, and I feel so weak today and my workout this morning was insanely bad.
How often do you use cypro?

 

[brix]

It does feel emotionally blunting during use I agree, and working out is SUCH a struggle. I had about 1.5mg last night, and I feel so weak today and my workout this morning was insanely bad.
How often do you use cypro?

Not very often. I will say when I took cypro and tyromix it negated the negative effects of cypro. Gained muscle easily without fatigue.

 

[Lokzo]

tyromix

Ahhh nice.

Am I missing something here... Isn't there a direct negative feedback when using real thyroid hormones?!