Cannabinoid System

[trainman04]

Hello. Can someone give me help me out.. I have so many genes for low functioning Cannabinoid System which I believe has lead to an enlarged amygdala.


SNP>

rs1049353 linked to the gene CNR1. Your genotype is TT, which is observed in 3% of all individuals reported.

• The T allele may cause lower CB1 receptor numbers and less CB1 activation, although this has not been experimentally confirmed (R).
• With this variation, the receptors also don't become significantly less sensitive when activated (R)

rs7766029 CC 18%

rs806377 CC 26%

Then I got these Genes>

CRHR1 gene
Corticotrophin release hormone receptor 1 (CRHR1) is a receptor for the hormone CRH. Antalarmin blocks this receptor.
CRHR1 promotes anxiety in part by reducing cannabinoids in our amygdala. This happens when CRHR1 activation increases FAAH in the amygdala, which causes a reduction in the endocannabinoid anandamide (AEA).
Diseases associated with CRHR1 include generalized anxiety disorder, IBS, obesity and depression (R, R2). CRHcauses fear and anxiety (R, R2) via CRHR1 (R) and major depression (R)

CNR1
CB1 receptors are found in particularly high density in the hippocampus and amygdala.
It's better to have this gene increased most of the time.
Chronic stress in mice without CB1 receptors show an enlarged fear center or amygdala (dendrites) ?. In humans, regular cannabis use can effectively dampen activation of the amygdala in response to stressful conditions ?.



I believe all these Cannabinoid mutations added up and causing my anxiety . People usually just have 1 of these mutations but I got multipel... Please help how do I fix this ??



I made a list gathered from selfhacked site that I will try to increase my cannabinoid system

cb1

Galantamine
Butyrate
Tylenol
Kava
Genistein
EGCg
Honokiol
Fish oil/DHA



cb2

Echinacea
Diindolylmethane
Lactobacillus acidophilus

I just took some inositol low dose and Holy shit do I feel happy..... It increases Cannabinoid function. I was expecting less anxiety which I did get but I feel like I also took a dose of phenibut.

whats the half life of inositol anyone know?
also whats the d aspartic acid half life? I might just take d aspartic acid instead or pure NMDA.. Since the cannabinoid reduces fear/anxiety by activating the NMDA system I think. Because there is no effective way to increase the cannabinoid system or increase the amount of cannabinoid CB1/cb2 receptors.

And since low activity cannabinoid system is linked to enlarged amygdala and if I somehow fix it how long will it take for my enlarged amygdala to go back to normal size? is that possible?

 

[sekio]

Stop trying to play backseat geneticist and contact a psychotherapist or medical doctor that can help you develop a treatment program for your anxiety.

I just took some inositol low dose and Holy shit do I feel happy.

Congratulations, you've proven the placebo effect is a thing. Inositol is effectively sugar and, being highly polar, is not going to cross BBB. But if you find inositol works for you, go ahead and supplement with it all you like, it won't hurt anywhere except your wallet.

Because there is no effective way to increase the cannabinoid system or increase the amount of cannabinoid CB1/cb2 receptors.

Except exercise and aerobic activity and sugar and the like.[ref1][ref2][ref3]

And since low activity cannabinoid system is linked to enlarged amygdala and if I somehow fix it how long will it take for my enlarged amygdala to go back to normal size? is that possible?

"It's not the size that matters, it's how you use it"

I swear, if you spent half the amount of effort you spend posting here on reading PubMed...

Please, go see a specialist instead of wasting your time and effort by doing this sort of self-diagnosis. If you don't have a suffficient level of education on chemistry and biology you're going to just be grasping at straws. Go back to basics and start from the symptom presentation, and quit hyperfocusing on individual genes and chemicals. A holistic approach is going to provide much more fulfilling results.

 

[trainman04]

inositol works im confident not placebo im not one of those type of dudes that fall for the placebo effect I know when I feel something . Why did it work immediately for me? Because I have a low functioning cannabinoid system. It worked for me so it must have crossed the BBB....
rs1049353 linked to the gene CNR1. Your genotype is TT, which is observed in 3% of all individuals reported.

 

[sekio]

Everyone "falls for the placebo effect". It's not something that you can consciously ignore, it's a result of expectation biases. Because you expect inositol will produce a positive effect, it does. It's worth doing some reading on.

Inositol is FDA GRAS (Generally Recognized As Safe) so according to the FDA it is not a pharmaceutical and is safe to consume as an inert filler. There are no studies that show consuming inositol does anything to modulate mood or the cannabinoid system.

 

[trainman04]

Everyone "falls for the placebo effect". It's not something that you can consciously ignore, it's a result of expectation biases. Because you expect inositol will produce a positive effect, it does. It's worth doing some reading on.

Inositol is FDA GRAS (Generally Recognized As Safe) so according to the FDA it is not a pharmaceutical and is safe to consume as an inert filler. There are no studies that show consuming inositol does anything to modulate mood or the cannabinoid system.

idk selfhacked listed it as an option to increase CB1
it sourced this
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1323208/

No I dont think everyone falls for the placebo effect im not gonna bother read the article you linked because I know myself better than a study does and I think everyone is different.

 

[sekio]

That study doesn't talk about the effects of inositol supplementation, it's instead about the unique activity of WIN55.212-2 at raising Ca+ concentration in certain cells ...

The [intracellular] calcium rise was WIN-specific, being essentially absent in cells treated with other classes of cannabinoid agonists, including Δ9-tetrahydrocannabinol, HU-210, CP55,940, 2-arachidonoylglycerol, methanandamide, and cannabidiol.

No I dont think everyone falls for the placebo effect

Study after study has proven that placebo effects are a real thing - and curiously the effect is present in everyone, even people who are outright told they are taking placebo will report effects, or people who simply don't believe such a thing exists.

im not gonna bother read the article you linked because I know myself better than a study does

If that were the case why are you bothering with reading blogs, forums, and running DNA tests? Once you reach this point, it seems less like scientific method and more like wishful thinking.

 

[Cotcha Yankinov]

It is true that the placebo effect can still occur when people are straight up told that they are receiving a placebo.

Placebo response rate for depression patients is something like 30% trainman, thats nothing to be sneezed at. None of us should assume we are special and impervious to the placebo effect, least of all somebody who is indeed mentally ill.

Sometimes people smoke weed for their first few times and deny that they are high or at least consciously/subjectively feel any different, while they are clearly high from an outsider's point of view. On the other hand you can give somebody catnip, tell them its weed, and then they will claim that they are high. This is a tricky business we're in, keep your mind open

 

[trainman04]

yes for depressed patients.. My issue is social anxiety.. and Suddenly when I started taking inositol Im more confident and less anxiety outside... I dont think placebo can do that.

 

[trainman04]

Are the NMDA and cannabinoid + cb1/cb2 linked?? Low cannabinoid is linked to enlarged amygdala but high cannabinoid is smaller amygdala, my question is how does the cannabinoid surpress the amygdala? is it by activating the cb1/cb2 receptor in the amygdala or by activatin the NMDA to surpress the amygdala? and how does the NMDA surpress the amygdala? I know when cb1/cb2 are activated it stops cortisol or something from going in to the amygdala... or something similar. if the cannabinoid surpresses the amygdala by activating the NMDA. I might aswell just take Pure NMDA instead since there are no effective ways in increasing expression of cannabinoid cb1 by a lot or increasing the amoung of cb1 receptors.

 

[sekio]

The placebo effect is found in all sorts of medicine, from treating infections to weight loss and depresssion, anxiety is no exception: [ref1][ref2][ref3]

Placebos are actually most effective when the person taking them believes there is some causal relation; for instance a study where people were treated with placebo sublingual sprays labeled either 'oxytocin' or 'serotonin' resulted in the people who believe they received "serotonin" reporting reduced depression and those given "oxytocin" had lower stress, anxiety, and depression.[ref]

What's even stranger is that the placebo effect works even when people know that they are taking placebos.[ref]

since there are no effective ways in increasing expression of cannabinoid cb1 by a lot or increasing the amoung of cb1 receptors.

Both consuming sugar and exercise can increase the sensitivity of CB1 receptors[ref] and treatment with cannabinoids theselves can also increase the expression of CB1 receptors. [ref] So run a 5k, smoke a fat blunt and eat some sugary stuff... see how you feel

You should try doing some research sometime, you might learn something new.

 

[trainman04]

I would do research but im so fatigued its impossible for me..
I think weed decreases CB1 ... cant find the study now tho.. i think it increased it in the beginning but long term decreased cb1

ok if the placebo effect is so good then go give PILLS to cancer patients and watch them be cured.

also
The T allele of rs1049353 may cause lower receptor numbers and less activation. With this variation, the receptors also don't become significantly less sensitive when activated (R) - i.e. you don't build up tolerance.
I have TT

 

[Coolwhip]

They may not be cured, but a large percentage of them will report feeling the effects of the "medicine". Honestly, I don't think anyone should be wasting their time in this thread, it's obvious you lack the basic knowledge necessary to take part in most discussions taking place in this subforum and have less than no desire to attain it.

Here I'll cut and paste something you must have missed when you were selectively copying single lines of text to support your own biases.

"The T allele may cause lower CB1 receptor numbers and less CB1 activation, though this has not been experimentally confirmed"

Not to mention your own text comes out of a study concerning ulcerative colitis and chron's.

Really, I am having trouble getting past the fact that within a few lines of each other you find

"The T allele of this polymorphism exerts some level of protection against stress and depression." and "...each T causes...a higher stress response, anxiety, a higher risk for depression"

 

[trainman04]

Does low functioning/low receptors cannabinoid system cause anything else besides low functioning NMDA system?

 

[sekio]

If you want a classical presentation of "low functioning cannabinoid system" look at the effects of rimonabant, it's a CB₁ antagonist that was marketed as an appetite reducer but pulled off market because of a greatly increased risk of major depression and suicide.

The primary effect was reduction in appetite and desire to eat, but there are other effects as detailed below.

Data from clinical trials submitted to regulatory authorities showed that rimonabant caused depressive disorders or mood alterations in up to 10% of subjects and suicidal ideation in around 1%, and in Europe it was contraindicated for people with any psychiatric disorder, including depressed or suicidal individuals.

Additionally, nausea and upper respiratory tract infections were very common (occurring in more than 10% of people) adverse effects; common adverse effects (occurring in between 1% and 10% of people) included gastroenteritis, anxiety, irritability, insomnia and other sleep disorders, hot flushes, diarrhea, vomiting, dry or itchy skin, tendonitis, muscle cramps and spasms, fatigue, flu-like symptoms, and increased risk of falling.

[...]

When the EMA reviewed postmarketing surveillance data, it found that the risk of psychiatric disorders in people taking rimonabant was doubled.

 

[trainman04]

If you want a classical presentation of "low functioning cannabinoid system" look at the effects of rimonabant, it's a CB₁ antagonist that was marketed as an appetite reducer but pulled off market because of a greatly increased risk of major depression and suicide.

The primary effect was reduction in appetite and desire to eat, but there are other effects as detailed below.

those are all my symptoms.
I wish I knew how to fix low cb

 

[Limpet_Chicken]

Smoke weed?

And as far as reducing fear, etc. its NMDA ANTagonists that will function pretty effectively as such. A NMDA agonist behaves on the other hand as a convulsant poison that would do the opposite. And excitotoxins produce PERMANENT damage. They quite literally burn brain cells out. Fried extra-crispy.

And the placebo effect is an awful lot more powerful than you give it credit for. Even people given a placebo and actually told that what they are given contains no medicine of any kind, can react to it. Animals can display placebo responses, and even the human immune system can react to them.

 

[trainman04]

doesent smoking weed decrease cb??? atleast after a period of weeks? initially it increeases.. or am i wrong

So which one increases CB1/cb2? thc or CBD?


thc and cbd is found in marijuana right? And marijuana, weed, cannabis and pot are all the same thing right? just different names?
(sorry im complete noob to this dont know anything)
ALso what is cbd oil? is that same as cbd just a different way of taking it?


Are there any other important important ingredients in marijuana? or just these 2 that been studied the most?


should I just go with marijuana instead of just going with only thc or cbd? just to make sure im getting all the benefits for my cannabinoid system?
So for me the best way would be to take marijuana pills Low dosage once a day? Does marijuana have a long half life?


hmm can someone explain this

according to this https://herb.co/marijuana/news/build-cannabis-tolerance


Earlier research has found that chronic THC treatment decreases the amount of CB1 receptors expressed in a cell. In the science world, this is called downregulation.


so Marijuana ony increases it initially but long term decreases??

 

[sekio]

Tolerance to cannabis is generally pretty dose-specific, what's important to remember is that THC is only a partial agonist of CB₁ so it produces much less downregulation than a full-agonist like JWH018 or the like. Plenty of people report using marijuana or its derivatives for long-term treatment of several chronic conditions successfully. Recreational users do develop tolerance too but generally pretty heavy usage has to be involved before the drug produces seemingly no effect.

THC and CBD are the two most widely investigated plant cannabinoids, THC is a CB₁ partial agonist and CB₂ agonist, CBD is a CB₁ antagonist and CB₂ agonist. Differing phenotypes of cannabis will produce different amounts of these, many popular recreational strains are almost exclusively THC whereas medicinal strains tend to have more CBD.

Both THC and CBD are not water soluble and are either dosed as smoke or vapour (via smoking/vaporization) or orally in oil of some sort (c.f. Marinol pills, cannabis edibles of all sorts). Eating marijuana itself won't produce an effect most of the time because the cannabinoids are in a pharmacologically inactive carboxylic acid form that needs to be treated with heat to release the active CBD/THC. It's also worth mentioning that CBD can convert into THC in acidic conditions.

If you have a hypoactive cannabinoid system then the logical thing to do would be try some sort of THC preparation, either smoking small amounts of cannabis flowers, or a low-dosage (5mg maybe) edible.

 

[Weltmeister]

It's also worth mentioning that CBD can convert into THC in acidic conditions.

Can you provide a source for this ? Id be interested in reading it

 

[trainman04]

Tolerance to cannabis is generally pretty dose-specific, what's important to remember is that THC is only a partial agonist of CB₁ so it produces much less downregulation than a full-agonist like JWH018 or the like. Plenty of people report using marijuana or its derivatives for long-term treatment of several chronic conditions successfully. Recreational users do develop tolerance too but generally pretty heavy usage has to be involved before the drug produces seemingly no effect.

THC and CBD are the two most widely investigated plant cannabinoids, THC is a CB₁ partial agonist and CB₂ agonist, CBD is a CB₁ antagonist and CB₂ agonist. Differing phenotypes of cannabis will produce different amounts of these, many popular recreational strains are almost exclusively THC whereas medicinal strains tend to have more CBD.

Both THC and CBD are not water soluble and are either dosed as smoke or vapour (via smoking/vaporization) or orally in oil of some sort (c.f. Marinol pills, cannabis edibles of all sorts). Eating marijuana itself won't produce an effect most of the time because the cannabinoids are in a pharmacologically inactive carboxylic acid form that needs to be treated with heat to release the active CBD/THC. It's also worth mentioning that CBD can convert into THC in acidic conditions.

If you have a hypoactive cannabinoid system then the logical thing to do would be try some sort of THC preparation, either smoking small amounts of cannabis flowers, or a low-dosage (5mg maybe) edible.

but can THC increase the AMOUNT of Receptors? Inositol can activate my cb1 receptors if I wanted that. But I need more CB1 receptors.
Does thc also increase Anandamide? What is Anandamide? and what is FAAH and can thc increase that too? can someone give me a brief explanation?

oh so a low dose edible? but didnt u say u cant take it orally?

so I take a low dose of thc once a day? What are the normal dosages for thc? Also what does a THC preparation contain besids thc itself? Unimportant stuff?
should i just go for plain marijuana just to make sure im getting all the cannabinoid system benefits. sorry for the 20 questions