Cyproheptadine's Effect On Dopamine

[milk_lover]

For the people who find cypro making them tired/depleted. It is probably due to the dose. If you look at the Wikipedia page, the concentration needed to antagonize the 5-HT1 and 5-HT2 "receptors" is about 2-3 nM/L. This is achievable with even 1mg cypro. The dopamine "receptors" D1, D2, and D3 are also antagonized by cypro. For D1 and D2, the concentration needed is about 100nM/L, which is achievable with 8mg single dose cypro.
Cyproheptadine - Wikipedia, the free encyclopedia
Given that long half life of cypro (9 hours) taking 4mg a few times a day can also probably achieve it over a few days. The D3 receptor is antagonized at concentrations of 8 nM/L, so taking lower dose cypro seems to have predominantly anti-serotonin effect withouht antagonizing dopamine except possibly D3. It is the dopamine antagonism at higher doses that probably makes some people feel like not doing anything.
Once again, Peat's knowledge is hard to deny given his recommendations of taking cypro at 1mg for general purposes and 2mg only for very serious conditions like cancer.

per day or per dose, haidut? If I take 1mg three or four times a day, would it still antagonize the D3 receptor?

 

[Such_Saturation]

Well wikipedia says D3 agonists like 7-OH-DPAT, pramipexole, and rotigotine, among others, display antidepressant effects in rodent models of depression.

 

[jyb]

For the people who find cypro making them tired/depleted. It is probably due to the dose. If you look at the Wikipedia page, the concentration needed to antagonize the 5-HT1 and 5-HT2 "receptors" is about 2-3 nM/L. This is achievable with even 1mg cypro. The dopamine "receptors" D1, D2, and D3 are also antagonized by cypro. For D1 and D2, the concentration needed is about 100nM/L, which is achievable with 8mg single dose cypro.
Cyproheptadine - Wikipedia, the free encyclopedia
Given that long half life of cypro (9 hours) taking 4mg a few times a day can also probably achieve it over a few days. The D3 receptor is antagonized at concentrations of 8 nM/L, so taking lower dose cypro seems to have predominantly anti-serotonin effect withouht antagonizing dopamine except possibly D3. It is the dopamine antagonism at higher doses that probably makes some people feel like not doing anything.
Once again, Peat's knowledge is hard to deny given his recommendations of taking cypro at 1mg for general purposes and 2mg only for very serious conditions like cancer.

Even 0.25 or 0.5mg can ruin the first few days of taking cypro depending on the individual. It may normalise fine after but you have to plan ahead and be ready for a sacrifice.

 

[haidut]

per day or per dose, haidut? If I take 1mg three or four times a day, would it still antagonize the D3 receptor?

Like I said in my post - single doses of cypro would achieve those concentrations but if you take lower concentrations for longer it may get to that level given the long half life. I think 1mg twice a day or 2mg once a day is enough for most people to experience the benefits without antagonizing the D3 receptor too much.

 

[haidut]

Even 0.25 or 0.5mg can ruin the first few days of taking cypro depending on the individual. It may normalise fine after but you have to plan ahead and be ready for a sacrifice.

Agreed, I think this is why Peat recommends no more than 0.5mg - 1mg for most people unless they have a very serious condition where antagonism of D3 is not the most critical worry.

 

[milk_lover]

Agreed, I think this is why Peat recommends no more than 0.5mg - 1mg for most people unless they have a very serious condition where antagonism of D3 is not the most critical worry.

Yesterday I took more than 16mg and I slept about 15 hours straight without any interruption and I missed work :) It was one of my most restful sleep ever and I didn't wake up with headache or any bad mood. So I am trying to gauge what works for me the best. I already emailed my line manager so no worries related to work. The work can always wait. I will try to lower the dose because I cannot afford to sleep this much everyday.

 

[DaveFoster]

I've been taking 16 mg for a while. The dopamine antagonism is pretty rough; ADHD does not help.

 

[milk_lover]

I've been taking 16 mg for a while. The dopamine antagonism is pretty rough; ADHD does not help.

So do you feel unmotivated from that dose? If so, why are you keeping it at that high of a dose?

 

[DaveFoster]

So do you feel unmotivated from that dose? If so, why are you keeping it at that high of a dose?

Because I'm pretty mentally ill; fibromyalgia is also reduced with a dose that high. I'm swapping it out for caffeine, which seems to be working better.

 

[narouz]

I can't say what went on with my dopamine when I was taking fairly high doses of cyproheptadine.
First time I took it I took about 4 mg, and I slept straight through from midnight to noon with no waking up.
Left me feeling a little foggy that Saturday, but I could sleep late and rest--I'd planned it that way.
I was in a pretty stressed out condition in those days and couldn't sleep well.
Cyproheptadine was great as a kind of emergency fix for that.

I tried taking it at about 2mg/day levels for about a week.
Many on here said the next-day-sleepiness/fogginess would gradually normalize.
I didn't continue the experiment long enough to see if that was true for me.

I now use it at low doses, like .5mg, before bed if I really want to feel confident of getting good sleep.

I'm not sure exactly what dopamine inhibition feels like,
but for me the next day effect always seems to be--
to one degree or another depending upon dosage--
a not unpleasant (if you don't have to work) grogginess or fuzziness.
Not a depressed feeling.
Feels like I got deep rest/sleep I was needing, but that there is a kind of recovery period the next day--that fuzziness or driftiness.

 

[NathanK]

I envy all of you. I miss those days when i felt something on Cypro. The sleep was some of the most blissful ive ever had

 

[Birdie]

For the people who find cypro making them tired/depleted. It is probably due to the dose. If you look at the Wikipedia page, the concentration needed to antagonize the 5-HT1 and 5-HT2 "receptors" is about 2-3 nM/L. This is achievable with even 1mg cypro. The dopamine "receptors" D1, D2, and D3 are also antagonized by cypro. For D1 and D2, the concentration needed is about 100nM/L, which is achievable with 8mg single dose cypro.
Cyproheptadine - Wikipedia, the free encyclopedia
Given that long half life of cypro (9 hours) taking 4mg a few times a day can also probably achieve it over a few days. The D3 receptor is antagonized at concentrations of 8 nM/L, so taking lower dose cypro seems to have predominantly anti-serotonin effect withouht antagonizing dopamine except possibly D3. It is the dopamine antagonism at higher doses that probably makes some people feel like not doing anything.
Once again, Peat's knowledge is hard to deny given his recommendations of taking cypro at 1mg for general purposes and 2mg only for very serious conditions like cancer.

Thank you. This info takes away anxiety I had about dose and effects.

 

[member 6316]

so the reason cypro works so well is because it decreases serotonin???

 

[bboone]

Agreed, I think this is why Peat recommends no more than 0.5mg - 1mg for most people unless they have a very serious condition where antagonism of D3 is not the most critical worry.

i am considering trying cypro, but in all honesty, i don't feel as if my serotonin is particularly high. however, the issue for me seems to be that my dopamine receptors have become extremely desensitized (after taking relatively high doses of ashwagandha extract over a period of two months), and so the "reward mechanism" has disappeared almost entirely from my life. does this make taking cypro sound like a bad idea? i sleep well, have morning wood and my appetite is always very high. i just don't have an intact motivational mechanism, which makes quite a few things frustrating.

 

[InChristAlone]

i am considering trying cypro, but in all honesty, i don't feel as if my serotonin is particularly high. however, the issue for me seems to be that my dopamine receptors have become extremely desensitized (after taking relatively high doses of ashwagandha extract over a period of two months), and so the "reward mechanism" has disappeared almost entirely from my life. does this make taking cypro sound like a bad idea? i sleep well, have morning wood and my appetite is always very high. i just don't have an intact motivational mechanism, which makes quite a few things frustrating.

Have you tried caffeine? I can't imagine that cypro would reset dopamine receptors since it can at high enough dose antagonize them. Whenever I use caffeine I get quite a lot of motivation. But....for me it ends in hypomania so I don't partake.

 

[bboone]

Have you tried caffeine? I can't imagine that cypro would reset dopamine receptors since it can at high enough dose antagonize them. Whenever I use caffeine I get quite a lot of motivation. But....for me it ends in hypomania so I don't partake.

i've been drinking coffee every day since i was 12. up to a gallon a day for some periods.. i found that ashwagandha probably "downregulated" my serotonin receptors (as well as had some interactions with GABA receptors, although i'm not sure how this works), so now i have to try and correct this

 

[InChristAlone]

i've been drinking coffee every day since i was 12. up to a gallon a day for some periods.. i found that ashwagandha probably "downregulated" my serotonin receptors (as well as had some interactions with GABA receptors, although i'm not sure how this works), so now i have to try and correct this

If you drink a lot of coffee maybe then your dopamine isn't sensitive to it anymore. I find caffeine works best when it's not abused. Seems most people just chronically take it so any increase in feel good hormone is just getting you back to baseline. Which is how an addiction works as well. You could try cypro just to see how it feels though.

 

[bboone]

If you drink a lot of coffee maybe then your dopamine isn't sensitive to it anymore. I find caffeine works best when it's not abused. Seems most people just chronically take it so any increase in feel good hormone is just getting you back to baseline. Which is how an addiction works as well. You could try cypro just to see how it feels though.

i definitely agree. i sometimes quit coffee for a month or two just to get the initial effect of it back, but usually i just drink it out of etiquette and habit. plus, i like the taste.

 

[Frankdee20]

i've been drinking coffee every day since i was 12. up to a gallon a day for some periods.. i found that ashwagandha probably "downregulated" my serotonin receptors (as well as had some interactions with GABA receptors, although i'm not sure how this works), so now i have to try and correct this

Ashwaganda effects 5ht1A (VIA AGONISM) making them desensitized. That is an auto receptor for directing Serotonin, and we all know what happens when we desensitize 1A. The herb indirectly does something with 5ht2A as well. It upregulates them, and creates more. This is great if you want to trip out on LSD, but not great for other things. Also, that much coffee will block GABA to the point where you upregulate to compensate for the antagonism.

 

[bboone]

Ashwaganda effects 5ht1A (VIA AGONISM) making them desensitized. That is an auto receptor for directing Serotonin, and we all know what happens when we desensitize 1A. The herb indirectly does something with 5ht2A as well. It upregulates them, and creates more. This is great if you want to trip out on LSD, but not great for other things. Also, that much coffee will block GABA to the point where you upregulate to compensate for the antagonism.

i didn't mean to imply that i drink a gallon of coffee daily - i don't. i drink two strong cups nowadays. do you have any suggestions as to what i could do to correct the negative effects of my ashwagandha usage?