Question about how cypro induces weight gain

[PointOutside]

I'm seeing how Cypro induced weight gain on the majority of subjects in every study I've come across. The issue is I can't see whether this weight gain is induced by the increase in appetite or by some other mechanism. I really like Cypro and would like to take 0.5-1mg a day for a month with two days off every week but I worry about the weight gain. I am taking thyroid (cypro increased my need for thyroid). Typically without Cypro I get by with low dose T3 but on Cypro I had to nearly double my thyroid dose to reach 98.6 F and I understand why. I'm just worried about the weight gain. I am waiting to see more peoples experience with 10-Methoxy-Harmalan before I experiment with it. I can easily control my urge to overeat, I just want to see if the weight gain is induced by more complex mechanisms than just an increase in appetite. I also don't each much starch so there's that too.

Can anyone share their weight gain experiences with Cypro at doses up to 1mg a day? Anyone take it longer term without any weight gain? There are other threads about this and I've read the majority of them but I never found any discussion on the mechanism that Cypro induces weight gain.

 

[Mauritio]

Probably D2 antagonism

 

[PointOutside]

Probably D2 antagonism

right, but if one were to address this through another route (D2 agonism) could the weight gain issues be suppressed outside of overeating?

 

[Mauritio]

right, but if one were to address this through another route (D2 agonism) could the weight gain issues be suppressed outside of overeating?

Possibly.

 

[redsun]

I'm seeing how Cypro induced weight gain on the majority of subjects in every study I've come across. The issue is I can't see whether this weight gain is induced by the increase in appetite or by some other mechanism. I really like Cypro and would like to take 0.5-1mg a day for a month with two days off every week but I worry about the weight gain. I am taking thyroid (cypro increased my need for thyroid). Typically without Cypro I get by with low dose T3 but on Cypro I had to nearly double my thyroid dose to reach 98.6 F and I understand why. I'm just worried about the weight gain. I am waiting to see more peoples experience with 10-Methoxy-Harmalan before I experiment with it. I can easily control my urge to overeat, I just want to see if the weight gain is induced by more complex mechanisms than just an increase in appetite. I also don't each much starch so there's that too.

Can anyone share their weight gain experiences with Cypro at doses up to 1mg a day? Anyone take it longer term without any weight gain? There are other threads about this and I've read the majority of them but I never found any discussion on the mechanism that Cypro induces weight gain.

Also, probably a very stupid question, but what's everyones opinion on low dose Adderall in combination with Cypro in the short term? Before every getting into the RP sphere I was prescribed Adderall XR which I took 1-4 times a month when needed.

Its from histamine antagonism since brain histamine reduces appetite through increased leptin sensitivity mainly.

Taking adderall alongside cypro will make adderall less effective. Do not take these together it doesnt make sense to take them together for any reason.

 

[PointOutside]

Its from histamine antagonism since brain histamine reduces appetite through increased leptin sensitivity mainly.

Taking adderall alongside cypro will make adderall less effective. Do not take these together it doesnt make sense to take them together for any reason.

Is there any safe way around the histamine antagonism? Or would you think it's better to use a different serotonin antagonist if I wanted to avoid this altogether? My questions may seem simple but I'm still learning. Thank you.

 

[redsun]

Is there any safe way around the histamine antagonism? Or would you think it's better to use a different serotonin antagonist if I wanted to avoid this altogether? My questions may seem simple but I'm still learning. Thank you.

No not really with cypro. Metergoline which is mostly a serotonin antagonist and dopamine agonist and doesnt affect histamine directly may be good. Better diet and specific nutrients help reduce serotonin and inhibit its release. This is the main way anyone should focus on first.

 

[PointOutside]

No not really with cypro. Metergoline which is mostly a serotonin antagonist and dopamine agonist and doesnt affect histamine directly may be good. Better diet and specific nutrients help reduce serotonin and inhibit its release. This is the main way anyone should focus on first.

No of course, my entire goal is to minimize serotonin without the need for any sort of direct pharmaceutical intervention. I also want my metabolism to be fueled by thyroid and not stress hormones and Cypro really exposed my underlying state. Waking temp dropped almost 2 F since starting Cypro and I upped my thyroid dose to compensate. Just really enjoying having a clear head with Cypro, especially after the most difficult semester of my life. Makes me feel way less autistic. Strangely on cypro my urge to check this forum goes down, as does my worry about my health issues. Living in the moment if that makes sense, without feeling rigid when around other people.

 

[redsun]

No of course, my entire goal is to minimize serotonin without the need for any sort of direct pharmaceutical intervention. I also want my metabolism to be fueled by thyroid and not stress hormones and Cypro really exposed my underlying state. Waking temp dropped almost 2 F since starting Cypro and I upped my thyroid dose to compensate. Just really enjoying having a clear head with Cypro, especially after the most difficult semester of my life. Makes me feel way less autistic. Strangely on cypro my urge to check this forum goes down, as does my worry about my health issues. Living in the moment if that makes sense, without feeling rigid when around other people.

Cypro reduces glutamate neurotransmission and as well as cholinergic neurotransmission. This (especially reducing glutamate too much) seriously impairs metabolism since glutamate is a critical component of a normal metabolism. Thats why your waking temp drops. Its kind of silly don't you think, taking a drug which is dramatically reducing your temps (which means it is reducing your own thyroid's ability to produce heat from metabolism, because your metabolism is literally slower) and then taking thyroid to deal with that. Just avoid cypro from the get go and work on other less extreme routes than taking such a strong CNS downer and taking thyroid which is just stimulating your CNS again anyway.

It also indirectly reduces other neurotransmitters and androgens through histamine antagonism which can also drop temps.

You should really only take something like cypro if you have severe histamine issues and only take it while you try to change your diet and lifestyle around to reduce histamine.

 

[PointOutside]

Cypro reduces glutamate neurotransmission and as well as cholinergic neurotransmission. This (especially reducing glutamate too much) seriously impairs metabolism since glutamate is a critical component of a normal metabolism. Thats why your waking temp drops. Its kind of silly don't you think, taking a drug which is dramatically reducing your temps (which means it is reducing your own thyroid's ability to produce heat from metabolism, because your metabolism is literally slower) and then taking thyroid to deal with that. Just avoid cypro from the get go and work on other less extreme routes than taking such a strong CNS downer and taking thyroid which is just stimulating your CNS again anyway.

It also indirectly reduces other neurotransmitters and androgens through histamine antagonism which can also drop temps.

You should really only take something like cypro if you have severe histamine issues and only take it while you try to change your diet and lifestyle around to reduce histamine.

I understand. I have been progressively getting worse over the years and finding RP has tremendously helped. I admit, I can be quite impulsive to try new things (especially when I don't have enough knowledge) but when life has gotten increasingly more dull, when I have slowly lost my ability to socialize, when my mind is constantly plagued with anxiety, I tend to hyperfocus on the things that provide me relief. Cypro is incredible for me, and I don't want to take Cypro as a crutch. I just want to feel how I felt only a few years ago and I've tried so many things. I've hit all of the basics a long time ago, and have definitely learned a lot. I learned that starch destroys any progress I make, I've learned that prior to thyroid but after optimizing my diet I still can't have normal body temperature. I've tried maxing out my daily intake for the many, many crucial nutrients talked about here, and seemingly nothing fixes my issues. Hell, I even tried religion. Despite this, I'm actually an optimistic person, mainly because I've had many windows of clarity throughout this even if most days I feel like a sack of ***t. I have had zero emotion for so long, and in this moment I can feel. This is why I'm fascinated by Cypro right now. I know my gut is screwed up, I know I've had autistic symptoms my entire life (like this weird thing I do where I walk around my bed room flailing my hands multiple times a day - cypro removes a lot of the urge to do that. Still embarrassing to mention but obviously it's an indicator of something serotonin related) I struggle with high adrenaline, I can have 98.6 oral temperature and have my hands so cold that it freaks people out. My digestion is just screwed up horribly and cypro just makes me feel like it's a nonissue in a dramatically short amount of time.

Truthfully I don't know what my goal really is with taking serotonin antagonists, since that's just covering up a bigger issue. I just don't know what other avenues to take after I've exhausted so many others.

 

[redsun]

I understand. I have been progressively getting worse over the years and finding RP has tremendously helped. I admit, I can be quite impulsive to try new things (especially when I don't have enough knowledge) but when life has gotten increasingly more dull, when I have slowly lost my ability to socialize, when my mind is constantly plagued with anxiety, I tend to hyperfocus on the things that provide me relief. Cypro is incredible for me, and I don't want to take Cypro as a crutch. I just want to feel how I felt only a few years ago and I've tried so many things. I've hit all of the basics a long time ago, and have definitely learned a lot. I learned that starch destroys any progress I make, I've learned that prior to thyroid but after optimizing my diet I still can't have normal body temperature. I've tried maxing out my daily intake for the many, many crucial nutrients talked about here, and seemingly nothing fixes my issues. Hell, I even tried religion. Despite this, I'm actually an optimistic person, mainly because I've had many windows of clarity throughout this even if most days I feel like a sack of ***t. I have had zero emotion for so long, and in this moment I can feel. This is why I'm fascinated by Cypro right now. I know my gut is screwed up, I know I've had autistic symptoms my entire life (like this weird thing I do where I walk around my bed room flailing my hands multiple times a day - cypro removes a lot of the urge to do that. Still embarrassing to mention but obviously it's an indicator of something serotonin related) I struggle with high adrenaline, I can have 98.6 oral temperature and have my hands so cold that it freaks people out. My digestion is just screwed up horribly and cypro just makes me feel like it's a nonissue in a dramatically short amount of time.

Truthfully I don't know what my goal really is with taking serotonin antagonists, since that's just covering up a bigger issue. I just don't know what other avenues to take after I've exhausted so many others.

Yeh cypro is like alcohol in this way. Its obviously not damaging like alcohol, but its a downer and makes you forget about your problems and make them seem less problematic.

If you have bad digestion cypro will worsen it even more.

What you described (normal temps and cold extremities) has nothing to do with your thyroid. In fact when your metabolism burns through your glycogen quickly (which stimulants do and thyroid can do) this gets worse. Because the problem is noradrenaline is too high. It elevates in response to many things, and its highly implicated in being involved in autistic symptoms. It also promotes vasoconstriction in the extremities, hence ice cold hands if its bad enough. Sympathetic dominance, low cholinergic activity also causes terrible digestion.

The major neurotransmitter that antagonizes excess sympathetic activity and noradrenaline is acetylcholine. You probably need to raise this. This will help cold extremities, digestion and this will calm down the nervous system and reduce impulsive, "autism" related behaviors by giving your nervous system more inhibitory control over your behavior. A calm nervous system is also needed to socialize.

Acetylcholine speeds up brain function, is necessary for verbal fluency and thinking and calming the nervous system by antagonizing sympathetic activity, which can promote manic and odd behaviors.

 

[PointOutside]

Yeh cypro is like alcohol in this way. Its obviously not damaging like alcohol, but its a downer and makes you forget about your problems and make them seem less problematic.

If you have bad digestion cypro will worsen it even more.

What you described (normal temps and cold extremities) has nothing to do with your thyroid. In fact when your metabolism burns through your glycogen quickly (which stimulants do and thyroid can do) this gets worse. Because the problem is noradrenaline is too high. It elevates in response to many things, and its highly implicated in being involved in autistic symptoms. It also promotes vasoconstriction in the extremities, hence ice cold hands if its bad enough. Sympathetic dominance, low cholinergic activity also causes terrible digestion.

The major neurotransmitter that antagonizes excess sympathetic activity and noradrenaline is acetylcholine. You probably need to raise this. This will help cold extremities, digestion and this will calm down the nervous system and reduce impulsive, "autism" related behaviors by giving your nervous system more inhibitory control over your behavior. A calm nervous system is also needed to socialize.

Acetylcholine speeds up brain function, is necessary for verbal fluency and thinking and calming the nervous system by antagonizing sympathetic activity, which can promote manic and odd behaviors.

I've already attempted raising Acetylcholine by eating a LOT more choline with no difference. I've thought about it being acetylcholine for a long time, since I struggle with more than just autistic symptoms that match up with lowered acetylcholine. I have nonexistent dream recall, for example. I have experienced depersonalization as well, which I know is also involved. Basically I can check every symptom of low acetylcholine. I just can't raise it. I've noticed improvements in the past using methylfolate and b12 which should spare acetylcholine. My Vitamin D is well into the range, I've taken Thiamine longterm before to replenish it, and many other things. It seems like choline is the rate-limiting step in Acetylcholine synthesis but I confidently know I ate a huge amount of choline trying to assist with this. Is too much Acetylcholinesterase activity a possibility here? Sorry, I've only taken undergrad Biochem.

Also, couldn't excess Acetylcholine also contribute to cold hands and feet?

 

[redsun]

I've already attempted raising Acetylcholine by eating a LOT more choline with no difference. I've thought about it being acetylcholine for a long time, since I struggle with more than just autistic symptoms that match up with lowered acetylcholine. I have nonexistent dream recall, for example. I have experienced depersonalization as well, which I know is also involved. Basically I can check every symptom of low acetylcholine. I just can't raise it. I've noticed improvements in the past using methylfolate and b12 which should spare acetylcholine. My Vitamin D is well into the range, I've taken Thiamine longterm before to replenish it, and many other things. It seems like choline is the rate-limiting step in Acetylcholine synthesis but I confidently know I ate a huge amount of choline trying to assist with this. Is too much Acetylcholinesterase activity a possibility here? Sorry, I've only taken undergrad Biochem.

Also, couldn't excess Acetylcholine also contribute to cold hands and feet?

Do you take anything or consume anything that can reduce acetylcholine synthesis? For example, vitamin A, D, and K in high doses can reduce acetylcholine synthesis. So if you eat liver you could be getting a ton of vitamin A which will severely inhibit cholinergic function.

The synthesis of acetylcholine is most important. You make it and then the body can break it down as needed. Acetylcholinesterase is not as important so I doubt it can be too high but its possible. We want acetylcholine's action but usually lingering effects (due to inhibited breakdown) is not what is needed. If you ability to synthesize it is inhibited somehow, this is where the problem could start. Vitamin E and all of the B vitamins (but especially B1 and B5) increase synthesis.

It could be a problem of poor receptor function as well. In this case we want to potentiate and increase sensitivity of cholinergic receptors. Zinc can do this. Zinc also inhibits serotonin by increasing 5-HT1A's (serotonin's autoreceptor) sensitivity. It is also is the metal utilized in enzymes for the breakdown of endogenous opioids in the body (which can contribute to depersonalization along with excess serotonin).

Serotonin also reduces acetylcholine activity generally.

 

[PointOutside]

Do you take anything or consume anything that can reduce acetylcholine synthesis? For example, vitamin A, D, and K in high doses can reduce acetylcholine synthesis. So if you eat liver you could be getting a ton of vitamin A which will severely inhibit cholinergic function.

The synthesis of acetylcholine is most important. You make it and then the body can break it down as needed. Acetylcholinesterase is not as important so I doubt it can be too high but its possible. We want acetylcholine's action but usually lingering effects (due to inhibited breakdown) is not what is needed. If you ability to synthesize it is inhibited somehow, this is where the problem could start. Vitamin E and all of the B vitamins (but especially B1 and B5) increase synthesis.

It could be a problem of poor receptor function as well. In this case we want to potentiate and increase sensitivity of cholinergic receptors. Zinc can do this. Zinc also inhibits serotonin by increasing 5-HT1A's (serotonin's autoreceptor) sensitivity. It is also is the metal utilized in enzymes for the breakdown of endogenous opioids in the body (which can contribute to depersonalization along with excess serotonin).

Serotonin also reduces acetylcholine activity generally.

Lately I’ve pretty much dropped most supplements, all of the ones you’ve listed I’ve taken. I eat liver once a week. I’ve supplemented all of the B vitamins numerous times in my past. I’ve never paid too much attention to B5 however. I typically also eat oysters but once a week.

Regardless, this is a new direction I could take (or revisit I suppose) and maybe it’s what I need. I appreciate your responses, truly. I understand everything you’re saying which is nice. I’m upping the oysters for sure, and will try to delve deeper.

Thank you @redsun

 

[redsun]

Lately I’ve pretty much dropped most supplements, all of the ones you’ve listed I’ve taken. I eat liver once a week. I’ve supplemented all of the B vitamins numerous times in my past. I’ve never paid too much attention to B5 however. I typically also eat oysters but once a week.

Regardless, this is a new direction I could take (or revisit I suppose) and maybe it’s what I need. I appreciate your responses, truly. I understand everything you’re saying which is nice. I’m upping the oysters for sure, and will try to delve deeper.

Thank you @redsun

Yeh I can't eat even 3-4 oz of liver even once anymore as I get all these low acetylcholine symptoms. I actually had a period of months where I was doing weekly liver but for the life of me could not understand what happened as I lost my personality, sociability, intelligence, short and long term memory, even basic math was difficult, easily tired from exertion (Ach needed for muscle contractions), indigestion, very easily stressed by anything at all...

I finally let go of the liver. After 2-3 weeks I finally felt like my old self. Once my brain came back online basically, I eventually was able to properly investigate and figured out vitamin A excess was the culprit by dose-dependently inhibiting acetylcholine synthesis. Given my experience, I highly recommend not touching any liver from this point forward to get rid of this very high retinol intake which is inhibit Ach synthesis. It took me weeks from my last liver intake for everything to start working again. I am confident that you will see improvement if you stop the very high preformed retinol intake.

I actually repeated this experiment multiple times afterwards because I was skeptical that it was the vitamin A but I was right (eating liver, waiting weeks for the retinol to clear out my system) and the same thing happens every time. I tried taking cholinergic promoting supplements while I waited weeks, it never fixed it. Only time (waiting long enough) finally fixed it, because in the case of excess vitamin A intake, it is because Vitamin A dose-dependently inhibits the formation of acetylcholine that Ach stays low no matter what which puts you in a sympathetic dominance like state.

 

[PointOutside]

Yeh I can't eat even 3-4 oz of liver even once anymore as I get all these low acetylcholine symptoms. I actually had a period of months where I was doing weekly liver but for the life of me could not understand what happened as I lost my personality, sociability, intelligence, short and long term memory, even basic math was difficult, easily tired from exertion (Ach needed for muscle contractions), indigestion, very easily stressed by anything at all...

I finally let go of the liver. After 2-3 weeks I finally felt like my old self. Once my brain came back online basically, I eventually was able to properly investigate and figured out vitamin A excess was the culprit by dose-dependently inhibiting acetylcholine synthesis. Given my experience, I highly recommend not touching any liver from this point forward to get rid of this very high retinol intake which is inhibit Ach synthesis. It took me weeks from my last liver intake for everything to start working again. I am confident that you will see improvement if you stop the very high preformed retinol intake.

I actually repeated this experiment multiple times afterwards because I was skeptical that it was the vitamin A but I was right (eating liver, waiting weeks for the retinol to clear out my system) and the same thing happens every time. I tried taking cholinergic promoting supplements while I waited weeks, it never fixed it. Only time (waiting long enough) finally fixed it, because in the case of excess vitamin A intake, it is because Vitamin A dose-dependently inhibits the formation of acetylcholine that Ach stays low no matter what which puts you in a sympathetic dominance like state.

Makes sense. But I also had these issues during a time where I rarely ate liver or other high Vit A foods. I will cut out the liver either way but I wish there was a way to directly supplement and find out what higher acetylcholine would feel like.

Wait also, could this be connected to K2 giving my high serotonin symptoms? I am unable to take it.

 

[redsun]

Makes sense. But I also had these issues during a time where I rarely ate liver or other high Vit A foods. I will cut out the liver either way but I wish there was a way to directly supplement and find out what higher acetylcholine would feel like.

Wait also, could this be connected to K2 giving my high serotonin symptoms?

Vitamin K also inhibits acetylcholine synthesis just like vitamin A in low and increasing doses. Vitamin D upregulates tryptophan hydroxylase thats why taking too much is also not good if you have high serotonin.

 

[PointOutside]

Vitamin K also inhibits acetylcholine synthesis just like vitamin A in low and increasing doses. Vitamin D upregulates tryptophan hydroxylase thats why taking too much is also not good if you have high serotonin.

Making many connections right now. One time many years ago my doctor prescribed me 50000 IU Vit D for once a week use and that single dose sent me down a massive panic attack. It took a week to feel normal again. I was also always prone to panic from marijuana which I saw some links to acetylcholine before. I think acetylcholine really might just be the answer. Thank you @redsun I have some hope now. Last last question, is there a relation between Calcium intake and acetylcholine levels? I do feel a little bit better overall with supplemental calcium carbonate.

 

[redsun]

Making many connections right now. One time many years ago my doctor prescribed me 50000 IU Vit D for once a week use and that single dose sent me down a massive panic attack. It took a week to feel normal again. I was also always prone to panic from marijuana which I saw some links to acetylcholine before. I think acetylcholine really might just be the answer. Thank you @redsun I have some hope now. Last last question, is there a relation between Calcium intake and acetylcholine levels? I do feel a little bit better overall with supplemental calcium carbonate.

Besides the serotonin aspect, vitamin D reduces Ach synthesis in high doses. 50k is definitely a high dose. I am glad I helped you make some connections.

Calcium channels trigger neurotransmitter release generally. This includes acetylcholine:

"ACh release is triggered by calcium influx through specific presynaptic Ca2+ channels. The modulation of this calcium influx appears as the main mechanism through which ACh release is regulated. This can be achieved by direct modification of the presynaptic Ca2+ channel opening or indirectly by a change in the polarization level of the presynaptic membrane due to the opening or closing of other presynaptic channels (usually K+ channels). The increase in the intracellular Ca2+ concentration that triggers ACh release is also under the control of Ca2+ membrane exchanges and intracellular Ca2+ buffers. ACh synthesis that takes place in the cytoplasm of the terminal, can itself be modulated leading to changes in the quantity of ACh available for release. All these regulatory mechanisms can be initiated by the activation of presynaptic receptors to either ACh itself (autoreceptors) or to other transmitters (heteroreceptors). Most often, these presynaptic receptors seem to require the transducing role of G proteins and the involvement of various second messengers. Some illnesses concerning the cholinergic system can be related to a disfunction of one of these presynaptic regulatory mechanisms."

[Release of acetylcholine and its regulation] - PubMed

The mechanism of acetylcholine (ACh) release and its regulation is a widely studied subject still underdebated. Although the vesicular hypothesis for ACh release is at present largely accepted, alternative theories have been proposed. ACh release is triggered by calcium influx through specific...

pubmed.ncbi.nlm.nih.gov

So calcium triggers acetylcholine's release from its vesicles. This could be calcium helps when you intake it.

If you have other questions feel free to ask.

 

[PointOutside]

Besides the serotonin aspect, vitamin D reduces Ach synthesis in high doses. 50k is definitely a high dose. I am glad I helped you make some connections.

Calcium channels trigger neurotransmitter release generally. This includes acetylcholine:

"ACh release is triggered by calcium influx through specific presynaptic Ca2+ channels. The modulation of this calcium influx appears as the main mechanism through which ACh release is regulated. This can be achieved by direct modification of the presynaptic Ca2+ channel opening or indirectly by a change in the polarization level of the presynaptic membrane due to the opening or closing of other presynaptic channels (usually K+ channels). The increase in the intracellular Ca2+ concentration that triggers ACh release is also under the control of Ca2+ membrane exchanges and intracellular Ca2+ buffers. ACh synthesis that takes place in the cytoplasm of the terminal, can itself be modulated leading to changes in the quantity of ACh available for release. All these regulatory mechanisms can be initiated by the activation of presynaptic receptors to either ACh itself (autoreceptors) or to other transmitters (heteroreceptors). Most often, these presynaptic receptors seem to require the transducing role of G proteins and the involvement of various second messengers. Some illnesses concerning the cholinergic system can be related to a disfunction of one of these presynaptic regulatory mechanisms."

[Release of acetylcholine and its regulation] - PubMed

The mechanism of acetylcholine (ACh) release and its regulation is a widely studied subject still underdebated. Although the vesicular hypothesis for ACh release is at present largely accepted, alternative theories have been proposed. ACh release is triggered by calcium influx through specific...

pubmed.ncbi.nlm.nih.gov

So calcium triggers acetylcholine's release from its vesicles. This could be calcium helps when you intake it.

If you have other questions feel free to ask.

I am aware of many big issues with this but a long time ago I came across Chris Masterjohn and choline. There’s a tool on his website where you can upload your genome. I remember based on certain SNPs I have that I needed triple the choline intake but not sure if that’s actually relevant. I know RP isn’t big on the methylation thing but nothing brought me closer long term than all of that and it’s probably because of acetylcholine. Once again thank you. I don’t have any other questions and at this point I just need to try a few things and read more.