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Cyproheptadine Lowers Cortisol, Endorphins, HGH, Aldosterone

Discussion in 'Scientific Studies' started by haidut, Apr 9, 2015.

  1. haidut

    haidut Member

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    Ray's last newsletter focused on endorphins and NO in various pathologies, including cancer. I don't need to mention that cortisol is also something you want to keep low. More importantly, it seems that serotonin is the cause behind Cushing disease and/or elevated cortisol levels (Cushingoid syndrome) and anti-serotonergic drugs may help. Thus, people struggling with symptoms of high cortisol should probably have their blood serotonin checked.
    It looks like cyproheptadine is very effective at lowering cortisol in Cushing disease, and this study also shows that it is capable of lowering endorphins as well. Finally, there are studies on PubMed showing cyproheptadine lowers NO and fully stops the endotoxin process. Thus, cypro seems to cover all angles of the latest Peat newsletter and may server as substitute for naltrexone.
    Furthermore, it seems that the effects of cyproheptadine depend more on the frequency of administration than on the dose. Thus, taking 1mg several times a day is probably better than taking 4mg at once, and it has the added benefit of being not very sedative.
    Finally, if cyproheptadine acts to lower all these stress hormone it may be a good supplement to consider if someone is struggling with thyroid and not reacting well to it.
    Oh, and I forgot to mention - cyproheptadine also lowers adrenalin. The lowering of adrenalin and serotonin may explain why some people seem to feel like zombies after taking serotonin. If the stress hormones are lowered and the person feels like crap this reveals low metabolism. So, if cyproheptadine makes you feel like crap maybe try to increase thyroid dosage.

    http://www.ncbi.nlm.nih.gov/pubmed/2995088
    "...An increase in the plasma contents of beta-endorphin and beta-lipotrophin in the above patients has been found to be one of the factors conditioning an enhanced activity of the hypothalamic-pituitary-adrenal system. Treatment of the patients suffering from Itsenko-Cushing's disease with cyproheptadine (peritol) resulted in a decrease of the plasma beta-endorphin and beta-lipotropin, as well as a display in 60% of cases of clinical and laboratory remission. Absence of the clinical remission in some patients treated with peritol indicated a need for intervention in the metabolism of other monoamines involved in the modulation of the action of opioid neuropeptides on the activity of the hypothalamic-pituitary system."

    http://www.ncbi.nlm.nih.gov/pubmed/6096979
    "...The authors provide the data on the changes in the blood content of opioid neuropeptides in patients with Icenko-Cushing's disease treated with an antiserotonin drug peritol. The high content of beta-endorphine and beta-lipotropin in the patients' blood was one of the factors determining activation of the hypothalamus-pituitary-adrenal system. The treatment of patients with Icenko-Cushing's disease by peritol led to a decrease in the blood content of beta-endorphine and beta-lipotropin, promoting a clinical and laboratory remission in 60% of patients. Some patients treated with peritol did not develop a clinical remission. This indicates the necessity of acting on the metabolism of other monoamines involved in the modulation of the action of neuropeptides on the hypothalamus-pituitary system."

    http://www.ncbi.nlm.nih.gov/pubmed/6852218
    "...Experiments on male rats have shown that the inhibitory effect of peritol on the hypothalamohypophyseal-adrenal system (HHAS) is determined both by its influence on the regulatory mechanisms of the CNS and direct action on secretion and, possibly, synthesis of steroids. The degree of the antiserotonin and the HHAS-inhibiting effects depends on the frequency of drug administrations rather than on its dose. The experimental studies made it possible to successfully apply peritol to the treatment of inpatients suffering from Icenko-Cushing's disease. Almost 60% of the inpatients manifested a remission, which was confirmed by the reduced blood content of ACTH, hydrocortisone and aldosterone."

    http://www.ncbi.nlm.nih.gov/pubmed/1177986
    "...Experimental evidence suggests a central-nervous-system origin of Cushing's disease and a role for serotonin in the regulation of ACTH release. The efficacy of cyproheptadine therapy, therefore, was studied in three patients with such disease. Administration of 24 mg daily over a period of three to six months was associated with prompt and sustained clinical and laboratory remission. Lessening of the physical manifestations of hypercorticism occurred, together with marked improvement in muscular weakness. Urinary corticosteroid excretion and cortisol secretory rate returned to normal. The urinary corticosteroid response to dexamethasone (2 mg per day) became normal; a paradoxical increase followed 8 mg per day. Abnormal circadian periodicity of plasma cortisol concentrations persisted. Return of normal amounts of Stage III to IV sleep occurred in the one patient so studied, who previously had markedly decreased periods of these stages. Discontinuance of therapy in one patient was associated with return of laboratory evidence of hypercorticism."

    http://www.ncbi.nlm.nih.gov/pubmed/7017408
    "...To study the role of serotonin in regulating the release of aldosterone, we gave single, oral doses of cyproheptadine, an antiserotoninergic agent, to five normal volunteers with high aldosterone levels secondary to sodium deprivation and to 14 patients with aldosteronism (six with idiopathic aldosteronism due to bilateral adrenal hyperplasia and eight with adrenal adenoma). A diet containing 150 mmol of sodium was given to the patients with spontaneous aldosteronism, and one containing 10 mmol of sodium was given to the normal subjects, for three days before treatment and throughout the study. All subjects received dexamethasone, 2 mg daily. Serum aldosterone was measured with the subject in the recumbent position before cyproheptadine administration and at 30-minute intervals for two hours afterward. Serum aldosterone fell significantly (P less than 0.025) from the basal level in the patients with idiopathic aldosteronism due to hyperplasia. No fall was observed in the normal subjects or in the patients with adenoma. No changes were seen in renin activity, cortisol, sodium, or potassium, in any group after cyproheptadine. Suppression of aldosterone with cyproheptadine suggests a serotonin-mediated aldosterone-stimulating system. Hyperactivity of this system may be the cause of idiopathic aldosteronism associated with adrenal hyperplasia."

    http://www.ncbi.nlm.nih.gov/pubmed/180050
    "...The effect of cyproheptadine on plasma growth hormone and cortisol levels was studied in seven male volunteers with polygraphic sleep monitoring. Sleep-related growth hormone release was completely inhibited in three of the seven normal subjects by the intravenous infusion of cyproheptadine (5 mg) which was started at the onset of sleep. In the other four, growth hormone release during sleep was significantly decreased or delayed by cyproheptadine when the drug infusion was started at 7:00 p.m., 1-2 h before the onset of sleep. The usual increase in plasma cortisol in the early morning was completely suppressed in all five subjects given cyproheptadine infusions from 4:00 to 7:00 a.m. The intravenous infusion of cyproheptadine increased slow wave sleep, although the time from sleep onset to the first occurrence of slow wave sleep was not affected. In contrast, rapid eye movement sleep was significantly decreased by cyproheptadine. These results suggest that cyproheptadine inhibits growth hormone and ACTH secretion during sleep in man, possibly by antagonizing serotoninergic mechanisms although other actions of the drug are not ruled out."

    http://www.ncbi.nlm.nih.gov/pubmed/177441
    "...Our data suggest that Cypro can reduce pituitary-adrenal responsiveness by reducing plasma ACTH concentrations. If Cypro acts as a serotonin antagonist, our data lends support to the idea that serotoninergic mechanisms are important in the control of pituitary ACTH secretion in normal human subjects."

    http://www.ncbi.nlm.nih.gov/pubmed/177112
    "...Cyproheptadine administration resulted in marked reduction and complete inhibition of the GH and ACTH-cortisol responses to L-dopa in a group of healthy subjects. If this drug acts by antagonizing serotonin, as assumed, this study suggests that serotonin is also involved in L-dopa induced GH and ACTH release."

    http://www.ncbi.nlm.nih.gov/pubmed/1171350
    "...Our data suggest that the alterations in adrenal function in our patients may be related to elevated serum serotonin. If CYPRO acts by antagonizing serotonin, these data may give support to the idea of serotoninergic control of cortisol secretion."

    http://www.ncbi.nlm.nih.gov/pubmed/8796367
    http://www.ncbi.nlm.nih.gov/pubmed/8636284
    http://www.ncbi.nlm.nih.gov/pubmed/2542391
    http://www.ncbi.nlm.nih.gov/pubmed/2832287
    http://www.ncbi.nlm.nih.gov/pubmed/6265685
    http://www.ncbi.nlm.nih.gov/pubmed/7011596
    http://www.ncbi.nlm.nih.gov/pubmed/632998
     
  2. jyb

    jyb Member

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    It seems like the effects on slow wave sleep are more likely to happen when cypro is taken in advance (here, at least 1 hour prior to instead of after sleep onset). Which should make sense because that sleep phase occurs first and we need to give time for the drug to act. Note that they infuse it, so maybe this translates into a different conclusion for optimal speed/dose than with oral pills.

    Surprising how some of these hormones seem to be almost 100% eliminated by cypro (during some phases of sleep) yet there are not necessarily (negative) consequences in practice, why is the body even bothering with these?!...
     
  3. OP
    haidut

    haidut Member

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    The flight or fight response I guess. In organism that have no natural enemies, the cortisol and adrenalin release is almost non-existent. Since adaptation is the primary feature of consciousness, I suppose the existence of these hormones and our ability to release them in such large quantities speaks of the harsh times through which we lived and adapted to.
     
  4. jyb

    jyb Member

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    Does this mean risk of hyperglycaemia? Note that this was a long term treatment (1 month).

    INHIBITION OF THE INSULIN RESPONSE TO GLUCOSE AFTER TREATMENT WITH CYPROHEPTADINE
    http://onlinelibrary.wiley.com/doi/10.1111/j.1651-2227.1982.tb09456.x/abstract

     
  5. OP
    haidut

    haidut Member

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    Yeah, I have seen this study but if you search PubMed you will see other studies showing that the effects is dependent on dosage. Higher doses like 16mg-24mg do seem to reduce insulin, while lower doses like 4mg-12mg seem to actually reduce blood sugar. I have not had a problem with cypro when I take it, but maybe it's b/c I take it rarely so it don't get these effects form the study above.
     
  6. cantstoppeating

    cantstoppeating Member

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    I've been taking cyproheptadine for the last few days and I've noticed astounding visual clarity. Since I'm mostly on my computer, I've noticed that colours seems more vivid and text seems sharper.
     
  7. OP
    haidut

    haidut Member

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    Classic effect of lowering/blocking serotonin. Cypro is good stuff:):
     
  8. RPDiciple

    RPDiciple Member

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    Im gonna start up this for sure.

    I stuggle with some water retention, dark circles under eyes and some slow metabolism. So clearly i have high estrogen.

    How would you start the dosing and how high would you go and what would you look for when to stop?
     
  9. cantstoppeating

    cantstoppeating Member

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    I'm currently taking 1mg in the morning, with my first meal, and 1mg with my last meal before I go sleep.

    I've also noticed stable temperature. My waking temps are now closer to 37c/98.6f and peak to that temperature much more earlier in the day. Oh, and it's the first time my pulse is reaching a steady 90-100bpm as opposed to 80bpm.

    The zombie feeling I had previously has now gone since I made a point to take thyroid (I take 25mcg of T3 spread throughout the day, which has the activity of 1 grain), caffeine and vitamin B6 -- both of which are important for maintaining dopamine.
     
  10. RPDiciple

    RPDiciple Member

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    cool. How long have you been taking it for? what dosage did you start with?
    Have you noticed change in appetite? weight gain? thats what im afraid of :P but since reducing serotonin it should raise pulse,temp and metabolic rate like you talk about so it should be a good thing
     
  11. RPDiciple

    RPDiciple Member

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    Thats awesome, sounds like the same thing you get from low dose LSD :D
     
  12. cantstoppeating

    cantstoppeating Member

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    Yes, on the second day I noticed a ravenous appetite and I veered off my fat free diet to chow-down massive quantities of full fat cheddar cheese. Given my increases in temp and pulse, clear vision and better sleep it's clear my metabolism has increased and with it a demand for more calories. And given my height, size, muscle mass etc I'd estimate I was maintaining a 800 calorie deficit before taking cyproheptadine, so with the increase in metabolism my appetite caught up.

    And about weight, I've decided not to focus on calories but instead take enough to maintain my metabolic rate so that I can restore testosterone, DHT, progesterone to normal/high levels (largely by reducing serotonin and prolactin) which all have a slimming/fat-reducing effect.
     
  13. RPDiciple

    RPDiciple Member

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    Great. Did you start off with 1mg in the morning and 1mg in the evening or did you start off with a smaller dose? i think that would knock me off completely :P
     
  14. narouz

    narouz Member

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    Man, I wanna tell you:
    do Not start with anything other than very small doses
    unless you wanna be Knocked F**king OUT.

    I mean like 1/2mg tops!
    At bedtime.
     
  15. RPDiciple

    RPDiciple Member

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    yeah i know. Took 0.5mg yesterday at bedtime. Felt nothing so thats good. But i guess for max results its best to take 2 times a day? evening and morning? so that it lasts 24 hours
     
  16. cantstoppeating

    cantstoppeating Member

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    A few further things I've noticed are:

    -sleep has continued to be 10-12 hours in duration and waking up requires a lot more will power
    -poor erections and little to no libido
    -night vision is almost non-existent.

    It's clear that cyproheptadine has a slight dopamine lowering effect for me so I'm going to combine it with bromocriptine to maintain my dopamine levels (and also because a recent prolactin test showed my result as a few digits over the top reference range.)

    Yesterday I noticed how poorly I could see in the dark where otherwise I would see just fine. Faint rays of nearby street lights usually make it through my windows and I can easily manage to see my way around with my lights off, but yesterday I couldn't see anything. Total pitch black.

    I remember reading something about serotonin switching on the cones or rods in our eyes to favour a certain type of vision, perhaps this is what's going on.
     
  17. RPDiciple

    RPDiciple Member

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    hmm, wondering what to do.
     
  18. BobbyDukes

    BobbyDukes Member

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    Are you still trying to decide? lol

    I've been taking 0.5mg, each morning, for the last week or so. Decided that I am going to come off it today. I doubt I'll see withdrawal from that, but you never know. Maybe I'll get a bad headache, or something.

    It's a great drug for stopping the stress repsonse. The last week my feet have been warm all the time. That alone is an extremely interesting observation, in my case.

    Unfortunately, I don't have any T3 left at the moment. So, taking cypro is a bit pointless. I'm basically lowering my stress hormones, with a less than shoddy metabolism to step up and take their place. I guess I must have some kind of a metabolism though, if I've had warm feet all week. But, cypro also has a bunch of other weird effects which, I couldn't pin down whether I liked or not. I felt a marked decrease in my ability to focus and read things. My attention span was awful. It did feel ever so slightly anti-depressive but ,at the same time, it definitely increased anhedonia. Libido dissapeared (in some circumstances, that's probably a good thing). Sleep was better once I adapted to the dose (no sedation in the morning; slept all the way through, each night).

    There are other observations, But, that's all I have for now and, all in all, a mixed bag experience.

    Another reason I've stopped the cypro is because I am also going a week without caffeine (as a trial). Yesterday was the first day of my caffeine abstinstence (lol). All I did was sleep. Like, seriously sleep. And all the way through the night. So far today, no caffeine and no cypro. And I do feel more alert. I may get back on to caffeine at the end of the week, if I don't notice any benefits from stopping it.

    As for cypro, I may still use it as an occasional sleep aid.
     
  19. RPDiciple

    RPDiciple Member

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    Thank you.

    Im doing 1 mg before bed, i dont feel any effect from it. Im thinking of doing 2mg in the evening now but im tempted to try using it during daytime as well but im afraid of all the things u mentioned :P but i really want to lower my cortisol, aldosterone etc since i struggle with water retention esp and some estrogen
     
  20. OkayByTheSea

    OkayByTheSea Member

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    I have been taking Cypro (1 mg at bed time) with excellent results (better sleep, less stressful days).

    My question is around safety; for how long could one take Cypro safely.

    Regards,
    OBTS
     
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