Too Much Ashwagandha, Now Serotonin Syndrome? Please Help

[General Orange]

Oh I just read that CBD activates 5HT1A receptors

Agonistic properties of cannabidiol at 5-HT1a receptors. - PubMed - NCBI

You probably don't want that too much. An agonist will down-regulate receptors, making the next stimulus less effective, this has negative side effects and builds up tolerance. therefore it is better to use antagonists.

 

[edd00]

Theoretical yes, but if you want safest action, quit both for a few months. You could always reintroduce the Rhodiola later.

oh perfect. I will do that. Better safe than sorry! Thanks again. I will wait 6 weeks to start, hopefully I wont even need it.

Also is keeping my serotonin low in general with shredded carrots and b vitamins going to help upregulate/downregulate those receptors as well? because I can eat carrots all day lol

 

[General Orange]

@Frankdee20 In your case with anhedonia and pre-ejac, you want to fix the anhedonia first, then the pre-ejac. Coz fixing anhedonia will cause premature ejac, with most drugs.

 

[General Orange]

Also is keeping my serotonin low in general with shredded carrots and b vitamins going to help upregulate/downregulate those receptors as well? because I can eat carrots all day lol

Alas, I don't think they have direct effects like that on receptors.

“Endotoxin or other material absorbed from intestinal bacteria contributes to a variety of autoimmune problems, including thyroiditis (Penhale and Young, 1988). Combining an indigestible fiber, such as raw carrot, with mild germicides, such as vinegar and coconut oil, can improve the hormonal environment, while reducing the immunological burden.”

Ray Peat, PhD on the Benefits of the Raw Carrot – Functional Performance Systems (FPS)

 

[General Orange]

But I think especially the niacinamide will support the system to repair itself.

“Niacinamide, one of the B vitamins, provides energy to the mitochondrial system. Under stress and strong excitation, cells waste niacinamide NADH, but niacinamide itself has a sedative antiexcitatory effect, and some of its actions resemble a hormone. Estrogen tends to interfere with the formation of niacin from tryptophan. Tryptophan, rather than forming the sedative niacin (pyridine carboxylic acid), can be directed toward formation of the excitatory quinolinic acid (pyridine dicarboxylic acid) by polyunsaturated fats. Excitation must be in balance with a cell’s energetic resources, and niacinamide can play multiple protective roles, decreasing excitation, increasing energy production, and stabilizing repair systems. The stat of excitation and type of energy metabolism are crucial factors in governing cell functions and survival.” Ray Peat

 

[Nicole W.]

well last week I had stuffed eggplants and tomatoes (Mama's home cooking) and I was totally fine. No GERD. But that is an interesting aspect I did not consider, maybe I might be mildly allergic? I read that they do cause inflammation in many people anyways, perhaps best to just avoid it for now. That's too bad because I put ketchup on everything lol . Thanks for the tip!

Not all nightshades bother nightshade sensitive people. I can eat potatoes and eggplant with no problems at all. Tomatoes are semi ok. Peppers and Ashwagandha trigger a GERD reaction. Just FYI.

 

[SOMO]

Ashwaghanda is the strongest nightshade and it is related to Nicotine, which many people can not tolerate.
But whereas Nicotine has some pro-dopamine effects, Ashwaghanda has very little and it can raise cortisol which is the opposite of why many people use it.

Ashwaghanda seems to cause GI distress in a lot of people, so you can be sure it's pro-dopamine effect is not strong enough to counteract the pro-serotonin effects it also seems to have.

I think Ashwaghanda might be useful short term in a small subset of people. Definitely a powerful herb that shouldn't be used long term.

Not all nightshades bother nightshade sensitive people. I can eat potatoes and eggplant with no problems at all. Tomatoes are semi ok. Peppers and Ashwagandha trigger a GERD reaction. Just FYI.

Supposedly some of the negative effects of tomatoes can be reduced by removing the seeds (who has time for that?) and eating the tomatoes alongside something containing cholesterol (like meat.) RP also says that tomatoes contain significant amounts of serotonin.

 

[edd00]

Alas, I don't think they have direct effects like that on receptors.


Ray Peat, PhD on the Benefits of the Raw Carrot – Functional Performance Systems (FPS)

I see but still good to know!

I was also thinking of trying beta-alanine. I've been browsing these forums a lot now people say good things about it.

Also does ashwaghanda only downregulate 5ht1 receptor, or other 5ht receptors too?

BTW I am super thankful that rhodiola is an option for me to upregulate 5ht1, glad I took them together!!

 

[edd00]

Not all nightshades bother nightshade sensitive people. I can eat potatoes and eggplant with no problems at all. Tomatoes are semi ok. Peppers and Ashwagandha trigger a GERD reaction. Just FYI.

good to know! I will research this more thank you!

 

[Arrade]

So ashwagandha has serotonin effects?
This is bad news as I was hoping to supplement in order to help heal my thyroid.
I cannot tolerate serotonin, i couldnt tolerate 1 mg of MB

 

[edd00]

Ashwaghanda is the strongest nightshade and it is related to Nicotine, which many people can not tolerate.
But whereas Nicotine has some pro-dopamine effects, Ashwaghanda has very little and it can raise cortisol which is the opposite of why many people use it.

Ashwaghanda seems to cause GI distress in a lot of people, so you can be sure it's pro-dopamine effect is not strong enough to counteract the pro-serotonin effects it also seems to have.

I think Ashwaghanda might be useful short term in a small subset of people. Definitely a powerful herb that shouldn't be used long term.



Supposedly some of the negative effects of tomatoes can be reduced by removing the seeds (who has time for that?) and eating the tomatoes alongside something containing cholesterol (like meat.) RP also says that tomatoes contain significant amounts of serotonin.

Raise cortisol, really? that is not what I signed up for! Well thankfully I used it for only a month. I guess its only good for those who's dopamine is naturally high

 

[edd00]

You probably don't want that too much. An agonist will down-regulate receptors, making the next stimulus less effective, this has negative side effects and builds up tolerance. therefore it is better to use antagonists.

I see, I was using it to help up-regulate the cbd receptors I lost in the hippo campus with heavy marijuana use in the past.

edit study

Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users. - PubMed - NCBI

 

[General Orange]

Also does ashwaghanda only downregulate 5ht1 receptor, or other 5ht receptors too?

BTW I am super thankful that rhodiola is an option for me to upregulate 5ht1, glad I took them together!!

Actually, it desensitize 5-HT1a but sensitive the 5HT2. It supposedly works around the receptors via the mRNA this could be lead to permanent effects. It also has effects on the GABA system.
Also it increases testosterone and downregulates estrogen. Ashwagandha raises testosterone and downregulates estrogen receptor

Ashwagandha appears to enhance signalling through GABAA receptors in a similar manner as scutellaria baicalensis, which seem to underlie the sleep enhancement and possibly anxiolytic effects of ashwagandha

Ashwagandha seems to have some evidence to suggest that it can increase 5-HT2 receptor signalling while reducing 5-HT1A receptor signalling, thus repartitioning serotonin signalling

Whatever causes the enhanced serotonergic signalling via 5-HT2 receptors ultimately prevents an excessive increase in nNOS and nitric oxide, which prevents excessive levels of corticosterone and thus exerts a neuroprotective and adaptogenic effect

Ashwagandha: Scientific review on benefits, side effects, dosage, and more.

 

[edd00]

Actually, it desensitize 5-HT1a but sensitive the 5HT2. It supposedly works around the receptors via the mRNA this could be lead to permanent effects. It also has effects on the GABA system.
Also it increases testosterone and downregulates estrogen. Ashwagandha raises testosterone and downregulates estrogen receptor




Ashwagandha: Scientific review on benefits, side effects, dosage, and more.

this explains the strength gains at the gym.

So I see that I need to upregulate 5-HT1A and downregulate 5-HT2. Rhodiola takes care of half the problem at least by up regulating 5-HT1A

.....also you said "permanent", that scares me lol. I hope 1 month use isn't enough to cause anything permanent

 

[General Orange]

I see, I was using it to help up-regulate the cbd receptors I lost in the hippo campus with heavy marijuana use in the past.

edit study

Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users. - PubMed - NCBI

Permanent changes from chronic use? not necessarily...
Does Marijuana Use Permanently Damage the Human Brain? - Medical Marijuana - ProCon.org

 

[edd00]

But I think especially the niacinamide will support the system to repair itself.

thanks!! will order it now!

 

[edd00]

Permanent changes from chronic use? not necessarily...
Does Marijuana Use Permanently Damage the Human Brain? - Medical Marijuana - ProCon.org

they are permanent only in the hippocampus for some reason. everywhere else they recover.

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

"Another interesting finding is that hippocampus did not show reversal of downregulation after abstinence: prolonged downregulation might contribute to long-term cognitive impairment in chronic daily cannabis smokers noted by some studies.39"

EDIT: CBD can help with CA1 subfields. not sure if its the same as whats downregulated with chronic marijuana use (those are CB1 receptors) but still its promising enough

 

[General Orange]

So ashwagandha has serotonin effects?
This is bad news as I was hoping to supplement in order to help heal my thyroid.
I cannot tolerate serotonin, i couldnt tolerate 1 mg of MB

First you have to understand the 5ht1a and 5ht2 systems before you can conclude that.
And methylene blue, is a MAOI with general targets of serotonin metabolism inhibition than Ashwagandha, who is more selective.
I think taking niacinamide with MB should negate the serotonin effects.
edit: or L-theanine

 

[General Orange]

they are permanent only in the hippocampus for some reason. everywhere else they recover.

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

"Another interesting finding is that hippocampus did not show reversal of downregulation after abstinence: prolonged downregulation might contribute to long-term cognitive impairment in chronic daily cannabis smokers noted by some studies.39"

EDIT: CBD can help with CA1 subfields. not sure if its the same as whats downregulated with chronic marijuana use (those are CB1 receptors) but still its promising enough

You should check out this post:
https://raypeatforum.com/community/...asing-serotonin-signalling.24057/#post-342459

 

[edd00]

You should check out this post:
https://raypeatforum.com/community/...asing-serotonin-signalling.24057/#post-342459

I see, more reason to downregulate 5HT2.

Well I haven't smoked in 6 years already and I don't plan on starting again.

What did you specifically want me to see on that post?